(AGENPARL) - Roma, 27 Giugno 2022

(AGENPARL) – SILVER SPRING lun 27 giugno 2022

Tafinlar (dabrafenib) In combination with trametinib for adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. 6/22/2022 4298-1: Conduct a clinical trial(s) in at least 80 patients with solid tumors with a BRAF V600E mutation to verify and describe the clinical benefit of dabrafenib in combination with trametinib, through more precise estimation of the ORR and mature response duration. Include patients with unresectable or metastatic solid tumors with a BRAF V600E mutation from the ongoing trial and from a prospectively conducted trial (which will exclude patients with melanoma, non-small cell lung cancer, anaplastic thyroid cancer, biliary tract cancer, gliomas and colorectal cancer). Follow all patients for at least 6 months from the onset of response to characterize the response rate and duration. 10/31/2028 Mekinist (trametinib) In combination with dabrafenib for adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options 6/22/2022 4297-1: Conduct a clinical trial(s) in at least 80 patients with solid tumors with a BRAF V600E mutation to verify and describe the clinical benefit of trametinib in combination with dabrafenib, through more precise estimation of the ORR and mature response duration. Include patients with unresectable or metastatic solid tumors with a BRAF V600E mutation from the ongoing trial and from a prospectively conducted trial (which will exclude patients with melanoma, non-small cell lung cancer, anaplastic thyroid cancer, biliary tract cancer, gliomas and colorectal cancer). Follow all patients for at least 6 months from the onset of response to characterize the response rate and duration. 10/31/2028 Kymriah (tisagenlecleucel) Treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy 5/27/2022 Conduct a randomized phase 3 trial in adult patients with r/r FL. Patients will be randomized to tisagenlecleucel or an investigator’s choice of regimens consistent with the standard of care. The primary endpoint will be PFS with secondary endpoints that include OS and ORR. 9/30/2028 Vijoice (alpelisib) Treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy 4/5/2022 4260-1: Conduct a multiregional clinical trial to verify and describe the clinical benefit of alpelisib film-coated tablets, through more precise estimation of confirmed ORR and mature response duration per blinded independent review, in adult and pediatric patients 2 years of age and older with PROS, including those with severe manifestations. Responding patients will be followed for at least 36 months from the onset of response, or until disease progression, whichever comes first. Evaluate a sufficient number of patients to characterize response rate and durability of response by PIK3CA mutation type, PROS subtype, and age. 8/31/2027 Pepaxto (melphalan flufenamide) In combination with dexamethasone for the treatment of adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD-38 directed monoclonal antibody 2/26/2021 4030-1: Submit the final study report and datasets from a randomized phase 3 clinical trial that verifies and describes the clinical benefit of melphalan flufenamide in patients with R/R MM. Patients should be randomized to receive melphalan flufenamide compared to standard therapy for R/R MM. The primary endpoint should be PFS assessed by an Independent Review Committee. The secondary endpoints should include overall response rate and OS. 2/28/2022 Gavreto (pralsetinib) Treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) 12/1/2020 3959-2: Submit the final report of integrated studies and datasets, to verify and further characterize the clinical benefit of pralsetinib for the treatment of patients with RET fusion-positive thyroid cancer who have received radioactive iodine (if appropriate for their tumor histology) to provide a more precise estimation of the BICR-assessed ORR and DOR in at least 50 patients in a variety of histologies after all responding patients have been followed for 12 months following onset of response or until disease progression, whichever comes first. 6/30/2025 Gavreto (pralsetinib) Treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy 12/1/2020 3959-1: Submit the final report including datasets from a multi-center, randomized, open-label trial comparing pralsetinib to investigator’s choice of either cabozantinib or vandetanib in multi-kinase inhibitor naïve patients with advanced or metastatic RET-mutant MTC to confirm the clinical benefit of pralsetinib with PFS  as a primary endpoint, as assessed by blinded independent central review.         1/31/2028 Scemblix (asciminib) Treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) 10/29/2021

4161-1: Conduct clinical study CABL001A2301 (ASCEMBL), A Phase 3, Multi-center, Open-Label, Randomized Study of Oral ABL001 vs. Bosutinib in patients with CML in CP, previously treated with 2 or more TKIs and provide the interim report with at least 24 months (96 weeks) follow-up of all patients to describe and confirm the clinical benefit of asciminib

7/31/2025 Tivdak (tisotumab vedotin-tftv) Treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy 9/20/2021 4131-1: Conduct the clinical trial innovaTV 301 titled, “Tisotumab Vedotin versus Chemotherapy in Recurrent or Metastatic Cervical Cancer” and provide the final OS and PFS analyses to describe and verify the clinical benefit of tisotumab vedotin in patients with recurrent or metastatic cervical cancer. 11/30/2024 Exkivity (mobocertinib) Treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy 9/15/2021 4148-1: Conduct a multicenter, randomized clinical trial and submit the final PFS results that verify and describe the clinical benefit of mobocertinib in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations 3/31/2024 Brukinsa (zanubrutinib) Treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen 9/14/2021 4128-1: Conduct a randomized clinical trial that verifies and describes the clinical benefit of zanubrutinib in patients with relapsed or refractory MZL. The trial should include sufficient representation of racial and ethnic minorities to better reflect the U.S. patient population and allow for interpretation of the results in these patient populations. The primary endpoint should be PFS, with secondary endpoints that include ORR and OS. 10/31/2028 Jemperli  (dostarlimab-gxly) Treatment for adult patients with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options 8/17/2021 4124-1: Conduct a clinical trial evaluating ORR, and DOR, to verify and describe the clinical benefit of Jemperli in patients with dMMR, recurrent or advanced solid tumors, including at least 300 patients across all tumor types, and including a sufficient number of patients and representation of tumor types (other than endometrial and GI tumors). In order to characterize response rate and DOR, patients should be followed for at least 12 months from the onset of response. Submit the datasets with final report. 10/31/2022 Truseltiq (infigratinib) Treatment of adult patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangement as detected by an FDA approved test 5/28/2021 4067-1: Submit the final PFS (as assessed by blinded independent review) analysis and interim OS  analysis at the time of final PFS analysis, including datasets from a randomized clinical trial comparing infigratinib to chemotherapy to verify and describe the clinical benefit of infigratinib in patients with advanced or metastatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement. Ensure that racial and ethnic minority subjects are adequately represented in the trial population, at a minimum, proportional to the prevalence of FGFR2 alterations in these subgroups in the US population. 6/30/2027 Lumakras (sotorasib) Treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. 5/28/2021 4071-1: Conduct a multicenter, randomized clinical trial and submit the final PFS results that verify and describe the clinical benefit of sotorasib in patients with locally advanced or metastatic NSCLC with a history of prior systemic therapy for advanced disease and whose tumors harbor KRAS G12C mutation. 7/30/2022 Rybrevant (amivantamab-vmjw) Treatment of adult patients with locally advanced or metastatic non small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum based chemotherapy. 5/21/2021 4070-1: Submit the final report, including datasets for PFS , DOR, and OS from a randomized clinical trial to verify and confirm the clinical benefit of amivantamab-vmjw for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. This could be from the ongoing clinical trial entitled, “A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin- Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer.” 2/28/2023 Keytruda (pembrolizumab) In combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. 5/5/2021 4033-1: Submit the final PFS and final OS analyses and datasets for the ongoing clinical trial KEYNOTE-811, “A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma” to verify and describe the clinical benefit of pembrolizumab with trastuzumab plus chemotherapy for patients with HER2-positive advanced or metastatic gastric or gastroesophageal adenocarcinoma. 9/30/2024 Zynlonta (loncastuximab tesirine) Treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. 4/23/2021 4029-1: Conduct a randomized, phase 3 clinical trial to verify and describe the clinical benefit of loncastuximab tesirine-lpyl in patients with R/R large B-cell lymphoma. The trial should include sufficient numbers of racial and ethnic minority patients to better reflect the U.S. patient population and allow for interpretation of the results in these patient populations. Patients should be randomized to receive loncastuximab tesirine-lpyl plus immunotherapy or immunochemotherapy. The primary endpoint should be PFS , with secondary endpoints that include OS and ORR. 12/31/2025 Jemperli (dostarlimab-gxly) Treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen.  4/22/2021 3909-1: Submit the final report and datasets from a clinical trial evaluating overall response rate, and duration of response, to verify and describe the clinical benefit of dostarlimab in patients with dMMR), recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen, in a sufficient number of patients. In order to characterize response rate and DOR, patients will be followed for at least 12 months from the onset of response. Alternatively, submit the final report and datasets from a randomized, phase 3 clinical trial that verifies and describes the clinical benefit of dostarlimab in patients with recurrent or primary advanced EC. Patients should be randomized to receive chemotherapy with or without dostarlimab. The primary endpoint should be PFS, with secondary endpoints that include OS and ORR 7/31/2022 Trodelvy (sacituzumab govitecan-hziy) Treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor 4/13/2021 4044-1: Submit the final study report and datasets for OS and PFS  from trial IMMU-132-13 titled “A Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician’s Choice in Subjects With Metastatic or Locally Advanced Unresectable Urothelial Cancer (TROPiCS-04)”, to verify and confirm the clinical benefit of sacituzumab in the urothelial cancer patient population. 4/30/2025 Yescarta (axicabtagene ciloleucel) Treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy 3/5/2021 1: A randomized phase 3 trial of axicabtagene ciloleucel in patients with relapsed or refractory FL. Patients will be randomized to axicabtagene ciloleucel or to an investigator’s choice of regimens consistent with the standard of care. The primary endpoint will be PFS, with secondary endpoints that include ORR and OS. 9/30/2027 Libtayo (cemiplimab-rwlc) Treatment of patients with metastatic basal cell carcinoma (mBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate 2/9/2021 4012-1: Submit the report and datasets for the 53 patients with mBCC from clinical study R2810 ONC 1620 evaluating ORR and DOR, to verify and describe the clinical benefit of cemiplimab in patients with mBCC who experienced progression of disease on hedgehog pathway inhibitor therapy or were intolerant of prior hedgehog pathway inhibitor therapy. To further characterize the magnitude and durability of responses in patients with mBCC, all patients will have the opportunity for 57 weeks of follow-up following completion of cemiplimab-rwlc. 2/28/2022 Tepmetko (tepotinib) Treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. 2/3/2021 4013-1: Submit the final reports including datasets from clinical studies to confirm and further characterize the clinical benefit of tepotinib for the treatment of patients with NSCLC harboring MET exon 14 skipping alterations who are treatment-naïve and who have previously received systemic therapy, by providing a more precise estimation of the blinded independent central review-assessed ORR and DOR. This report will contain data from patients with NSCLC harboring MET exon 14 skipping alterations; data from at least 130 patients who are treatment naïve, after all responders have been followed for at least 12 months from the date of initial response (or until disease progression, whichever comes first); and from at least 143 patients who have been previously treated with systemic therapy, after all responders have been followed for at least 6 months from the date of initial response (or until disease progression, whichever comes first). 4/30/2023 Darzalex Faspro (daratumumab and hyaluronidase-fihj) Treatment of patients with light chain (AL) amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone in newly diagnosed patients. 1/15/2021 3951-1: Submit the final study report and datasets from a randomized clinical trial to verify and further characterize the clinical benefit and safety of daratumumab subcutaneous for the treatment of patients with AL amyloidosis. This submission should include the final analysis and datasets of PFS or OS results. 6/30/2025 Danyelza (naxitamab) In combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. 11/25/2020 3950-1: Submit the final report, including datasets, from an ongoing multicenter clinical trial to verify and further characterize the clinical benefit of naxitamab for the treatment of patients with R/R neuroblastoma in combination with GM-CSF in bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy; and to provide a more precise estimation of ORR and DOR (according to the revised International Neuroblastoma Response Criteria by blinded independent review). Enroll a minimum of 80 patients with evaluable disease and systematically follow all responding patients for at least 12 months from the onset of response, or until disease progression, whichever comes first. Include subgroup analyses of ORR and DOR by prior anti-GD2 exposure, disease status (refractory vs. relapsed disease), anti-drug antibody (ADA) status (neutralizing antibody [nAb] positive versus nAb negative, ADA positive versus ADA negative), and area of disease involvement (bone marrow vs. bone) in the final report reflecting a sufficient number of patients in relevant subgroups. Derive the clinical data from a minimum of 6 study sites, with at least 5 patients enrolled per site in at least 5 sites. 9/30/2027 Gavreto (pralsetinib) Treatment of adult patients with metastatic RET fusion- positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.. 9/4/2020 3916-1: Submit the final report, including datasets, from an ongoing clinical trial to verify and further characterize the clinical benefit of pralsetinib for the treatment of patients with 1) treatment-naïve RET fusion-positive NSCLC and with 2) RET fusion-positive NSCLC who have previously received platinum chemotherapy to provide a more precise estimation of the BICR assessed ORR and DOR after all responders in the population of patients with treatment-naïve NSCLC (approximately 120 patients) have been followed for at least 12 months from the date of initial response (or until disease progression, whichever comes first) and after all responders in the population of patients with NSCLC previously treated with platinum therapy (87 patients) have been followed for at least 6 months.  10/30/2022 Blenrep (belantamab mafodotin-blmf) Treatment of adults with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent 8/5/2020 3800-1: Submit the final study report and datasets from a randomized phase 3 clinical trial that verifies and describes the clinical benefit of belantamab mafodotin in patients with R/R MM. Patients should be randomized to receive belantamab mafodotin compared to standard therapy for R/R MM. The primary endpoint should be PFS and secondary endpoints that include OS and ORR, as well as PRO. This trial should include a sufficient number of older patients (ages 65-74 and ≥75) and patients with extramedullary disease. 1/31/2023 Monjuvi (tafasitamab-cxix) In combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). 7/31/2020 3904-1: Submit the final report and datasets from a randomized, Phase 3 clinical trial to verify the clinical benefit of tafasitamab in patients with DLBCL. The trial should include sufficient numbers of racial and ethnic minority patients to better reflect the U.S. patient population and allow for the interpretation of the results in these patient populations. Patients should be randomized to receive immunotherapy and/or chemotherapy with or without tafasitamab and lenalidomide. The primary endpoint should be PFS, with secondary endpoints that include OS and ORR. 12/31/2025 Tecartus (brexucabtagene autoleucel) Treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). 7/24/2020 1: Complete additional follow-up of all 68 subjects treated with brexucabtagene autoleucel in ZUMA-2 Cohort 1 to a minimum of 18 months from the time of first response. Data will continue to be collected according to the ZUMA-2 protocol’s established schedule of assessments.
2: Conduct a study of brexucabtagene autoleucel treatment of subjects with relapsed or refractory mantle cell lymphoma who have not been exposed to a Bruton tyrosine kinase (BTK) inhibitor. A cohort of subjects naïve to BTK inhibitor therapy will be added to the ongoing ZUMA-2 study to fulfill this requirement. Eighty-six subjects will be enrolled. The primary efficacy endpoint will be objective response rate with a supportive efficacy endpoint of duration of response based on a minimum follow-up of 18 months after first objective disease response. 10/31/2025 Xpovio (selinexor) Treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma (FL), after at least 2 lines of systemic therapy. 6/22/2020 3866-1: Submit the final report and datasets from a randomized, double-blind, placebo-controlled phase 3 trial that verifies and describes the clinical benefit of selinexor in patients with relapsed or refractory DLBCL. Patients should be randomized to receive chemoimmunotherapy with or without selinexor. The primary endpoint should be PFS , with secondary endpoints that include OS and ORR. 4/30/2026 Tazverik (tazemetostat) Treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies. Treatment of adult patients with R/R FL who have no satisfactory alternative treatment options. 6/18/2020 3872-1: Submit the final report and datasets from a randomized, phase 3 clinical trial that verifies and describes the clinical benefit of tazemetostat in patients with R/R FL  whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test. The trial should include sufficient numbers of racial and ethnic minority patients to better reflect the U.S. patient population and allow for the interpretation of the results in these patient populations. Patients should be randomized to receive immunotherapy with or without tazemetostat. The primary endpoint should be PFS, with secondary endpoints that include OS and ORR.
3872-2: Submit the final report and datasets from a randomized, phase 3 clinical trial that verifies and describes the clinical benefit of tazemetostat in patients with R/R FL whose tumors do not have an EZH2 mutation as detected by an FDA-approved test. The trial should include sufficient numbers of racial and ethnic minority patients to better reflect the U.S. patient population and allow for the interpretation of the results in these patient populations. Patients should be randomized to receive immunotherapy with or without tazemetostat. The primary endpoint should be PFS, with secondary endpoints that include OS and ORR. 7/31/2025 Keytruda (pembrolizumab) Treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden high (TMB H) [=10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. 6/16/2020 3871-1    (S- 071): Submit the final report and datasets from clinical trials evaluating ORR and DOR, to verify and describe the clinical benefit of pembrolizumab in adult and pediatric patients with unresectable or metastatic TMB-H [=10 mutations/megabase (mut/Mb)] solid tumors (as determined by an FDA-approved test) that have progressed following prior treatment and who have no satisfactory alternative treatment options. A sufficient number of patients and representation of tumor types (other than lung cancers, MSI-H or dMMR cancers, or melanoma; and including CNS tumors that were determined to be TMB-H based on testing of tissue obtained prior to initiation of temozolomide chemotherapy), and with cancers having a TMB of 10 to <13 mut/Mb, will be evaluated to characterize response and DOR. A minimum of 20 pediatric patients will be studied. ORR and DOR will be assessed by independent central review for patients with cancers having a TMB of =10 mut/Mb, =10 mut/Mb to <13 mut/Mb, and =13 mut/Mb. All responding patients will be followed for at least 12 months from the onset of response. 12/31/2025 Zepzelca (lurbinectedin) Treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after prior platinum-based chemotherapy. 6/15/2020 3831-1: Submit the final report and datasets for the OS and PFS analysis as determined by an Independent Review Committee from a clinical trial to confirm the clinical benefit of lurbinectedin in SCLC that may inform product labeling. This could be from the Study titled, “Phase III Randomized Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus Cyclophosphamide, Doxorubicin and Vincristine (CAV) or Topotecan as Treatment in Patients With SCLC Who Failed One Prior Platinumcontaining Line (ATLANTIS)”. 2/28/2021 Rubraca (rucaparib) Treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy 5/15/2020 3833-1: Submit the PFS and OS analyses and datasets demonstrating clinical benefit of rucaparib from a phase 3 randomized trial in patients with mCRPC associated with homologous recombination deficiency who have been treated with androgen receptor directed therapy. The results may inform product labeling. 10/31/2025 Pomalyst (pomalidomide) Treatment of patients with AIDS-related Kaposi’s Sarcoma after failure of highly active antiretroviral therapy (HAART). 5/14/2020 3855-1: Submit the final report from a clinical trial evaluating ORR , DOR, and safety to verify and describe the clinical benefit of pomalidomide in patients with Kaposi sarcoma who are HIV positive (after failure of HAART) and HIV negative, that may inform product labeling. 12/31/2027 Pomalyst (pomalidomide)  Treatment of Kaposi’s Sarcoma in patients who are HIV-negative 5/14/2020 3855-1: Submit the final report from a clinical trial evaluating ORR, DOR, and safety to verify and describe the clinical benefit of pomalidomide in patients with Kaposi sarcoma who are HIV positive (after failure of HAART) and HIV negative, that may inform product labeling. 12/31/2027 Retevmo (selpercatinib)  Adult patients with metastatic RET fusion-positive Non-Small Cell Lung Cancer (NSCLC) 5/8/2020 3829-2: Submit a final report including datasets from an ongoing clinical trial to verify and further characterize the clinical benefit of selpercatinib for the treatment of patients with 1) treatment-naïve RET fusion-positive NSCLC and with 2) RET fusion-positive NSCLC who have previously received platinum chemotherapy that will provide a more precise estimation of the blinded independent central review assessed ORR  and DOR after all responders in the population of at least 65 patients have been followed for at least 12 months from the date of initial response (or until disease progression, whichever comes first) in patients with treatment-naïve NSCLC and after all responders have been followed for at least 6 months in the population of patients (at least 180 patients) with NSCLC previously treated with platinum therapy. 11/30/2021 Retevmo (selpercatinib) Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy 5/8/2020 3829-1: Submit the final report including datasets from a multi-center, randomized trial comparing selpercatinib to physician’s choice of approved therapies in patients with kinase inhibitor-naïve, progressive, advanced or metastatic RET-mutant MTC to confirm clinical benefit of selpercatinib with PFS as a key secondary end point as assessed by blinded independent central review. 10/31/2026 Retevmo (selpercatinib) Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). 5/8/2020 3829-3: Submit a final report including datasets, to verify and further characterize the clinical benefit of selpercatinib for the treatment of patients with RET fusion-positive thyroid cancer who have received radioactive iodine (if appropriate for their tumor histology) to provide a more precise estimation of the blinded independent central review-assessed ORR  and DOR  in at least 50 patients after all responding patients have been followed for 12 months following onset of response or until disease progression, whichever comes first. 12/31/2023 Tabrecta (capmatinib) Treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test 5/6/2020 3828-1: Submit the final reports including datasets from clinical studies to confirm and further characterize the clinical benefit of capmatinib for the treatment of patients with NSCLC whose tumors have a mutation that leads to MET exon 14 skipping who are treatment-naïve and who have previously received platinum-based chemotherapy, by providing a more precise estimation of the blinded independent central review-assessed ORR and DOR. This report will contain data from NSCLC patients whose tumors have a mutation that leads to MET exon 14 skipping; data from at least 60 patients who are treatment naïve, after all responders have been followed for at least 12 months from the date of initial response (or until disease progression, whichever comes first); and from at least 85 patients who have been treated with platinum-based therapy, after all responders have been followed for at least 6 months from the date of initial response (or until disease progression, whichever comes first). 2/28/2022 Pemazyre (pemigatinib) Treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. 4/17/2020 3801-1: Submit the results of a randomized trial demonstrating improvement of PFS or OS in patients with unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 gene fusion or rearrangement, to confirm clinical benefit of pemigatinib. 12/31/2026 Yervoy (ipilimumab) In combination with nivolumab, for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib 3/10/2020 3823-1: Submit the final report demonstrating an improvement in OS from a multicenter, randomized trial to confirm the clinical benefit of nivolumab in combination with ipilimumab over standard therapy in patients with advanced HCC, that may inform product labeling. Submit the datasets with the final report. 7/31/2024 Opdivo (nivolumab) In combination with ipilimumab, for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib 3/10/2020 3822-1: Submit the final report demonstrating an improvement in OS from a multicenter, randomized trial to confirm the clinical benefit of nivolumab in combination with ipilimumab over standard therapy in patients with advanced HCC, that may inform product labeling. Submit the datasets with the final report. 7/31/2024 Tazverik (tazemetostat) Treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.  1/23/2020 3787-1: Submit the final results from a confirmatory randomized trial in patients with epithelioid sarcoma to confirm clinical benefit and provide additional efficacy data that may inform product labeling for tazemetostat.
3787-2: Submit the final report and datasets for the final analysis of ORR and DOR for clinical trial EZH-202 titled, “A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma” to verify and confirm clinical benefit of tazemetostat, that may inform product labeling. An additional 25 patients from Cohort 6 beyond those included in the original NDA submission will be evaluated and all responding patients will be followed for at least 12 months from the onset of response. 9/30/2029 Brukinsa (zanubrutinib) Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 11/14/2019 3735-1: Complete and submit the final results of Trial BGB-3111-306 – the ongoing randomized, Phase 3 clinical trial of BRUKINSA in combination with rituximab versus bendamustine and rituximab in patients with previously untreated MCL. The primary endpoint is PFS as assessed by Independent Review Committee (IRC). OS is a key secondary endpoint. PFS and OS would be analyzed based on superiority testing. Enrollment of approximately 500 patients is expected 2/28/2027 Rozlytrek (entrectinib) Treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. 8/15/2019 3689-2: Submit the final report, including datasets, from ongoing and proposed trials conducted to verify and describe the clinical benefit of entrectinib, through more precise estimation of the ORR and mature response duration per independent review assessment, in adult and pediatric patients 12 years of age and older with solid tumors with a NTRK gene fusion and without a known acquired resistance mutation; are metastatic or would require surgical resection that would result in severe morbidity; and have no satisfactory alternative treatment or that have progressed following treatment. A sufficient number of patients will be evaluated to more precisely characterize response and durability of response for each of the following tumor types: pediatric solid tumors, CRC, CNS cancers, GYN cancers, and melanoma. A minimum of 40 patients with cancers other than pediatric solid tumors, CRC, CNS cancers, GYN cancers, melanoma, STS, non-small cell adenocarcinoma lung cancer, mammary analogue secretory carcinoma, and secretory breast cancer will also be studied. ORR and DOR will be assessed by independent central review and all responding patients will be followed for at least 12 months from the onset of response.
3689-1: Submit the final report, including datasets, from the first 54 patients with NTRK-fusion solid tumors enrolled across the ALKA, STARTRK-1 [NCT], and STARTRK-2 [NCT] studies to verify and describe the clinical benefit and further characterize the DOR in patients who achieved a complete or partial response to entrectinib. All responding patients will be followed for at least 2 years from the onset of response or until disease progression, whichever comes first. DOR will be assessed by independent central review. 3/31/2027 Polivy (polatuzumab  vedotin- piiq) In combination with bendamustine and a rituximab product for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least two prior therapies. 6/10/2019 3630-1: Complete Study GO39942, a randomized, double-blind, placebocontrolled trial that evaluates polatuzumab vedotin-piiq in combination with R-CHP versus R-CHOP in patients with previously untreated DLBCL. The primary endpoint would be PFS. Key secondary endpoints would include CR rate per independent review committee and OS.
3630-2: Complete Study MO40598, a randomized clinical trial that evaluates polatuzumab vedotin-piiq in combination with R-GemOx  versus R-GemOx alone in patients with relapsed or refractory large B-cell lymphoma. The primary endpoint would be OS. Key secondary endpoints would include PFS and CR rate. 6/30/2024 Balversa (erdafitinib)

Treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC), that has:

4/12/2019 3561-1: Submit the analysis, and datasets with the final report demonstrating clinical benefit of erdafitinib in patients with locally advanced and mUC with susceptible FGFR 3 or FGFR 2 genetic alterations from clinical trial BLC3001 entitled; “A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects with Advanced Urothelial Cancer and Selected FGFR Gene Aberrations.” 10/31/2022 Keytruda (pembrolizumab) Treatment of adults and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC) 12/19/2018 3546-1: Conduct and submit the results of a multicenter clinical trial to confirm the clinical benefit of pembrolizumab in patients with locally advanced or metastatic MCC who have not received prior systemic therapies for metastatic MCC. The trial will enroll at least 50 patients to be followed for a minimum of 12 months to establish the ORR and characterize the DOR. OS, which is a secondary endpoint, will be followed to maturity until at least 70% of patients have died, or for an additional 2 years beyond the primary data analysis cut-off, to characterize effects on survival. 12/30/2032 Vitrakvi  (Capsules) (larotrectinib) Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation; are metastatic or where surgical resection is likely to result in severe morbidity; and have no satisfactory alternative treatments or that have progressed following treatment 11/26/2018 3540-1: Submit the final report, including datasets, from ongoing and proposed trials conducted to verify and describe the clinical benefit of larotrectinib, through more precise estimation of the ORR and mature response duration per independent review assessment, in adult and pediatric patients with solid tumors with a NTRK gene fusion and without a known acquired resistance mutation; are metastatic or where surgical resection is likely to result in severe morbidity; and have no satisfactory alternative treatment or that have progressed following treatment. A sufficient number of patients will be evaluated to characterize response and durability of response for each of the following tumor types: CRC, NSCLC, CNS tumors, and melanoma. A minimum of 40 patients with cancers other than CRC, NSCLC, CNS tumors, melanoma, STS, thyroid cancer, infantile fibrosarcoma, and salivary cancers (e.g., BC, GI stromal tumors, cholangiocarcinoma, biliary tract cancers) will also be studied. ORR and DOR will be assessed by independent central review and all responding patients will be followed for at least 12 months from the onset of response. 8/31/2025 Keytruda (pembrolizumab) Treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib 11/9/2018 3492-1: Conduct and submit the results of one or more randomized trials to verify and describe the clinical benefit of pembrolizumab as compared to available therapy in patients with locally advanced, unresectable or metastatic HCC as demonstrated by an improvement in OS or a large improvement in PFS that is clinically meaningful. 10/31/2019 Opdivo (nivolumab) In combination with ipilimumab, is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR), metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan 7/10/2018 3449-1: Submit the final report, including datasets, from a randomized trial conducted to verify and describe the clinical benefit of nivolumab, administered in combination with ipilimumab, in patients with MSI-H or dMMR metastatic colorectal cancer. The trial will be designed to demonstrate a clinically meaningful improvement in PFS in patients randomized to receive nivolumab and ipilimumab as compared to patients randomized to receive nivolumab alone. In addition, the trial should evaluate for differences in OS between arms based on a pre-specified analysis. The analysis plan should describe the power for the OS analysis, as well as all assumptions made in determining the power. 7/31/2024 Yervoy (ipilimumab) In combination with nivolumab, is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR), metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan 7/10/2018 3450-1: Submit the final report, including datasets, from a randomized trial conducted to verify and describe the clinical benefit of ipilimumab, administered in combination with nivolumab, in patients with MSI-H or dMMR metastatic colorectal cancer. The trial will be designed to demonstrate a clinically meaningful improvement in PFS in patients randomized to receive ipilimumab and nivolumab as compared to patients randomized to receive nivolumab alone. In addition, the trial should evaluate for differences in OS between arms based on a pre-specified analysis. The analysis plan should describe the power for the OS analysis, as well as all assumptions made in determining the power. 7/31/2024 Blincyto (blinatumomab) Treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children 3/29/2018 3366-1: Complete a randomized trial and submit the final study report and data sets to verify and describe the clinical benefit of blinatumomab in adults with ALL in morphologic CR with detectable MRD, including efficacy and safety from protocol E1910: Combination chemotherapy with or without blinatumomab in treating patients with newly-diagnosed BCR-ABL-negative B lineage ALL.  Randomization of approximately 280 newly diagnosed patients is expected, and the primary endpoint is OS.
3366-2: Complete a randomized trial and submit the final study report and data sets to verify and describe the clinical benefit of blinatumomab in pediatric patients in morphologic CR with detectable MRD, including efficacy and safety from protocol AALL1331: Risk-stratified Phase III testing of blinatumomab in first relapse of childhood B-lymphoblastic leukemia (B-ALL). Enrollment of approximately 598 patients is expected. The primary endpoint is disease-free survival. 4/30/2025 Calquence (acalabrutinib) Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 10/31/2017 3291-1: Submit the complete final report and datasets demonstrating clinical efficacy and safety from a randomized, double-blind, placebo-controlled, clinical trial of Calquence in combination with standard immunochemotherapy versus immunochemotherapy alone in patients with MCL. 11/30/2024 Aliqopa (copanlisib) Treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies 9/14/2017 3273-1: In order to verify the clinical benefit of Aliqopa (copanlisib), submit the complete final clinical report and datasets from a randomized, double-blind, placebo-controlled trial of Aliqopa in combination with immunochemotherapy versus immunochemotherapy alone in patients with relapsed FL, MZL, SLL, or lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia. The primary endpoint is PFS. Enroll approximately 520 patients. 9/30/2022 Opdivo (nivolumab) For the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.  7/31/2017 3243-1: Submit the final report, including datasets, from trials conducted to verify and describe the clinical benefit of nivolumab 240 mg intravenously every two weeks in patients with MSI-H or dMMR CRC who have progressed following treatment with fluoropyrimidine, oxaliplatin and irinotecan, including at least 150 patients enrolled in BMS-initiated trials. In order to characterize response rate and duration, patients will be followed for at least 12 months from the onset of response. 9/30/2021 Keytruda (pembrolizumab) Treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or metastatic MSI-H or dMMR colorectal cancer that have progressed following treatment with a fluoropyrimidine, oxaliplatin and irinotecan 5/23/2017 3213-1: Submit the final report, including datasets, from trials conducted to verify and describe the clinical benefit of pembrolizumab 200 mg intravenously every three weeks in patients with MSI-H or dMMR  tumors including at least 124 patients with colorectal cancer enrolled in Merck-initiated trials; at least 300 patients with non-colorectal cancer, including a sufficient number of patients with prostate cancer, thyroid cancer, small cell lung cancer; and ovarian cancer; and 25 children. In order to characterize response rate and duration, patients will be followed for at least 12 months from the onset of response. 3/31/2023 Opdivo (nivolumab)

Treatment of adult patients with classical Hodgkin lymphoma that has relapsed or progressed after:

4/25/2017 3089-1: Conduct a randomized phase 3 clinical trial in classical Hodgkin lymphoma that verifies and isolates the clinical benefit of nivolumab for patients with classical Hodgkin lymphoma. The primary endpoint would be PFS as determined by an independent review committee. OS would be a key secondary endpoint. 12/31/2026 Tecentriq (atezolizumab) Patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 as determined by an FDA approved test or who are not eligble for any platinum-containing chemotherapy regardless of PD-L1 status.   4/17/2017 3196-1: Conduct clinical trial IMvigor130 entitled, “A Phase III, Randomized Study of Atezolizumab Alone and in Combination with Chemotherapy Versus Chemotherapy Alone in Participants with Untreated Advanced Urothelial Cancer”.  Submit the datasets with the final report. 11/30/2020 Bavencio (avelumab) Treatment of adults and pediatrics patients 12 years and older with metastatic merkel cell carcinoma (MCC). 3/23/2017 3185-1: Conduct and submit the results of a multicenter clinical trial confirming the clinical benefit of avelumab in patients with metastatic MCC who have not received prior systemic therapies for metastatic MCC. The trial will enroll at least 100 patients followed for a minimum of 12 months, in order to establish the objective response rate and characterize the durability of response for first-line treatment of metastatic MCC. All patients will be followed for OS until at least 70% of patients have died in order to characterize effects on survival. An analysis of OS compared to historical control data will be provided. 12/31/2026 Imbruvica (ibrutinib) For the treatment of patients with Marginal Zone Lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. 1/18/2017 3150-1: Submit the complete final report and data from a randomized, Phase 3 trial, comparing ibrutinib in combination with bendamustine and rituximab or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone versus bendamustine and rituximab or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in subjects with previously treated FL or MZL.  At least 50 enrolled subjects need to have a diagnosis of MZL.  The primary endpoint is PFS in the overall ITT population. 8/31/2019 Opdivo (nivolumab) For the treatment of classical Hodgkin Lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. 5/17/2016 3089-1: Conduct a randomized phase 3 clinical trial in classical Hodgkin lymphoma that verifies and isolates the clinical benefit of nivolumab for patients with classical Hodgkin lymphoma. The primary endpoint would be PFS as determined by an independent review committee. OS would be a key secondary endpoint. 12/31/2026 Beleodaq (belinostat) Treatment of relapsed or refractory peripheral T-Cell Lymphoma (PTCL) 7/3/2014 2178-2: Characterize the comparative efficacy and safety of belinostat when used in combination with a treatment regimen such as CHOP, versus the combination of pralatrexate plus CHOP, versus CHOP alone for the initial therapy of patients with PTCL. Perform a confirmatory, prospective randomized (1:1:1) trial of previously untreated patients with PTCL, with PFS as the primary efficacy endpoint. Enroll a sufficient number of patients to characterize the efficacy and safety of each drug added to CHOP, versus CHOP alone. The PFS endpoint should be determined by a blinded independent review committee. PFS analysis should be performed when the trial has experienced the planned number of events necessary for trial completion. Using the same data cutoff date as the PFS analysis, perform an interim analysis of OS. Submit a complete final report with all supporting datasets.
2178-1: Establish the optimal and safe dose of belinostat in combination with the CHOP regimen. Perform a Phase 1 dose finding trial of belinostat plus CHOP for the treatment of patients with PTCL. Enroll a sufficient number of patients to characterize the safety of belinostat in combination with the CHOP regimen. Submit a complete final report with all supporting datasets 1/31/2021 Imbruvica (ibrutinib) Treatment of patients with mantle cell lymphoma (MCL) 11/13/2013 2060-2: Complete and submit the final results of the ongoing randomized, double-blind, placebo-controlled Phase 3 clinical trial (PCI-32765MCL3002) of ibrutinib in combination with bendamustine and rituximab in patients with newly diagnosed MCL.  Enrollment of approximately 520 patients is expected.  The primary endpoint is PFS as assessed by investigators. OS is a key secondary endpoint.
2060-1: Continue follow-up of patients (on treatment and in protocol defined post-treatment follow-up) and submit a final analysis report of trial PCYC-1104-CA with a minimum follow-up of 24 months for each patient. If 24 months follow-up is not possible for certain patients, provide justification for each patient. In addition, submit detailed assessment information regarding all sites of extranodal disease at baseline and follow-up, including assessments for response and progression.  Summarize extranodal disease characteristics at baseline and at time of progression.  Request further documentation as necessary from clincial trial sites in order to summarize the details of the extranodal disease progression. 3/31/2019 Folotyn (pralatrexate) Treatment of relapsed or refractory peripheral T-Cell Lymphoma (PTCL) 9/24/2009 2179-2: Characterize the comparative efficacy and safety of  pralatrexate when used in combination with a treatment regimen such as CHOP, versus the combination of Beleodaq plus CHOP, versus CHOP alone for the initial therapy of patients with PTCL. Perform a confirmatory, prospective randomized (1:1:1) trial of previously untreated patients with PTCL, with PFS as the primary efficacy endpoint. Enroll a sufficient number of patients to characterize the efficacy and safety of each drug added to CHOP, versus CHOP alone. The PFS endpoint should be determined by a blinded independent review committee. PFS analysis should be performed when the trial has experienced the planned number of events necessary for trial completion. Using the same data cutoff date as the PFS analysis, perform an interim analysis of OS. Submit a complete final report with all supporting datasets.
2179-1 : Establish the optimal and safe dose of pralatrexate in combination with the CHOP regimen. Perform a Phase 1 dose-finding trial of pralatrexate plus CHOP for the treatment of patients with PTCL. Enroll a sufficient number of patients to characterize the safety of pralatrexate in combination with the CHOP regimen. Submit a complete final report with all supporting datasets. 6/30/2017 Clolar (clofarabine) Treatment of pediatric patients 1 to 21 yrs old with relapsed or refractory acute lymphocytic leukemia (ALL) after at least 2 prior regimens 12/28/2004 1253-2: Completion of a controlled clinical study to verify and describe the clinical benefit of clofarabine in pediatric ALL. Your proposed Phase 3 study to be possibly conducted by the COG does not appear to have a realistic chance of showing a clinical benefit of clofarabine in children with ALL in first relapse. Please submit a new protocol for a study to show clofarabine clinical benefit in children with ALL within 2 months of the date of this letter. Timelines for study start, completion and submission of the study report will also be submitted. Please request a meeting to discuss this protocol within 30 days of receipt of this letter, so that a meeting can be scheduled to occur about one month after receipt of the protocol 12/31/2019

Fonte/Source: http://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals