FDA Updates

FDA Updates

Recent Approvals from the U.S. Food and Drug Administration

Darzalex Faspro Approved to Treat Multiple Myeloma
The U.S. Food and Drug Administration has approved Janssen Biotech’s Darzalex Faspro (daratumumab and hyaluronidase-fihj) for adults with newly diagnosed, relapsed, or refractory multiple myeloma. This new product allows for subcutaneous dosing of daratumumab.

FDA Approves First Targeted Therapy to Treat Aggressive Form of Lung Cancer
The FDA has granted accelerated approval to Tabrecta (capmatinib) for the treatment of adults with non-small cell lung cancer that has spread to other parts of the body. Tabrecta, which is marketed by Novartis, is the first FDA-approved therapy to treat non-small cell lung cancer with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping).

The FDA also approved Foundation Medicine’s FoundationOne CDx assay (F1CDx) as a companion diagnostic for Tabrecta. Most patients had tumor samples that were tested for mutations that lead to MET exon 14 skipping using local tests and confirmed with the F1CDx, which is a next-generation sequencing based in vitro diagnostic device that is capable of detecting several mutations, including mutations that lead to MET exon 14 skipping

FDA Approves First Therapy for People with Lung and Thyroid Cancers with a Certain Genetic Mutation or Fusion
The FDA has granted accelerated approval to Loxo Oncology’s Retevmo (selpercatinib) capsules to treat three types of tumors – non-small cell lung cancer, medullary thyroid cancer, and other types of thyroid cancers – in people whose tumors have an alteration (mutation or fusion) in a specific gene (RET or “rearranged during transfection”). Retevmo is the first therapy approved specifically for cancer patients with the RET gene alterations.

Lynparza plus Bevacizumab Approved as Maintenance Treatment for Ovarian, Fallopian Tube, and Primary Peritoneal Cancers
The FDA has expanded the indication of AstraZeneca’s Lynparza (olaparib) to include its combination with bevacizumab for first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. The FDA has also approved Myriad Genetics’ Myriad myChoice® CDx as a companion diagnostic for Lynparza.

FDA Grants Accelerated Approval to Pomalyst for Kaposi Sarcoma
The FDA has expanded the indication of Celgene’s Pomalyst (pomalidomide) to include treating adults with AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy, as well as Kaposi sarcoma in adults who are HIV-negative.

FDA Approves Opdivo Plus Yervoy to Treat Certain Types of Metastatic Non-Small Cell Lung Cancer
The FDA has approved the combination of Opdivo (nivolumab) plus Yervoy (ipilimumab), both marketed by Bristol-Myers Squibb, as first-line treatment for people with metastatic non-small cell lung cancer whose tumors express PD-L1, as determined by an FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. The FDA also approved Agilent Technologies’ PD-L1 IHC 28-8 pharmDx as a companion diagnostic device for selecting people with non-small cell lung cancer for treatment with Opdivo plus Yervoy

Rubraca Granted Accelerated Approval for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer
The FDA has granted accelerated approval to Clovis Oncology’s Rubraca (rucaparib) for people with deleterious BRCA mutation-associated metastatic castration-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Rucaparib previously was granted breakthrough therapy designation for this indication.

FDA Approves First Drug for Fourth-Line Treatment of Advanced Gastrointestinal Stromal Tumor
The FDA has approved Qinlock (ripretinib) tablets as the first new drug specifically approved as a fourth-line treatment for advanced gastrointestinal stromal tumor (GIST), a type of tumor that originates in the gastrointestinal tract. Qinlock, which is marketed by Deciphera Pharmaceuticals, is indicated for adults who have received prior treatment with three or more kinase inhibitor therapies, including imatinib.

Tecentriq Approved as First-Line Treatment of Metastatic Non-Small Cell Lung with High PD-L1 Expression
Genentech’s Tecentriq (atezolizumab) has been approved for the first-line treatment of adults with metastatic non-small cell lung cancer whose tumors have high PD-L1 expression, with no EGFR or ALK genomic tumor aberrations. The FDA also approved Ventana Medical Systems’ Ventana PD-L1 (SP142) Assay as a companion diagnostic device for selecting people with non-small cell lung cancer for treatment with Tecentriq.

FDA Approves Lynparza to Treat Gene-Mutated Metastatic Castration-Resistant Prostate Cancer
AstraZeneca’s Lynparza (olaparib) has been granted FDA approval to treat adults with deleterious or suspected deleterious germline or somatic HRR gene-mutated metastatic castration-resistant prostate cancer who have progressed following prior treatment with enzalutamide or abiraterone. The FDA also approved Foundation Medicine’s FoundationOne CDx for selection of people with metastatic castration-resistant prostate cancer carrying HRR gene alterations and Myriad Genetic’s BRACAnalysis CDx test for selection of people with metastatic castration-resistant prostate cancer carrying germline BRCA1/2 alterations as companion diagnostic devices for treatment with Lynparza.

Alunbrig Approved as ALK-Positive Metastatic Non-Small Cell Lung Cancer Treatment
The FDA has approved Ariad Pharmaceuticals’ Alunbrig (brigatinib) for adults with ALK-positive metastatic non-small cell lung cancer as detected by an FDA-approved test. The FDA also approved Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit as a companion diagnostic for Alunbrig.

FDA Approves Opdivo Plus Yervoy and Chemotherapy for First-Line Treatment of Metastatic Non-Small Cell Lung Cancer
The FDA has approved the combination of Bristol-Myers Squibb’s Opdivo (nivolumab) plus Yervoy (ipilimumab) and two cycles of platinum-doublet chemotherapy as first-line treatment for people with metastatic or recurrent non-small cell lung cancer with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

Tecentriq Plus Avastin Approved for Unresectable Hepatocellular Carcinoma
The FDA has approved Tecentriq (atezolizumab) in combination with Avastin (bevacizumab), both marketed by Genentech, for people with unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy.

Cyramza Plus Erlotinib Gains FDA Approval as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer
Eli Lilly’s Cyramza (ramucirumab), in combination with erlotinib, has been approved by the FDA for first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 mutations.

FDA Approves Opdivo for Esophageal Squamous Cell Carcinoma
Bristol-Myers Squibb’s Opdivo (nivolumab) has been granted FDA approval to treat people with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy.

Zepzelca Granted Accelerated Approval to Treat Metastatic Small Cell Lung Cancer
The FDA has granted accelerated approval to Zepzelca (lurbinectedin) for adults with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. The FDA granted approval of Zepzelca to Pharma Mar S.A.

FDA Approves Mylotarg to Treat Children with CD33-Positive AML
The FDA has extended the indication of Wyeth Pharmaceuticals’ Mylotarg (gemtuzumab ozogamicin) for newly diagnosed CD33-positive acute myeloid leukemia to include pediatric patients one month and older.

FDA Approves Keytruda for Adults and Children with TMB-H Solid Tumors
Merck’s Keytruda (pembrolizumab) has been granted accelerated approval by the FDA for the treatment of adults and children with unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. The FDA also approved Foundation Medicine’s FoundationOneCDx assay as a companion diagnostic for Keytruda.

Tazverik Receives Accelerated Approval to Treat follicular Lymphoma
The FDA has granted accelerated approval to Tazverik (tazemetostat), an EZH2 inhibitor marketed by Epizyme, for adults with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies, as well as for adults with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options. The FDA also approved Roche Molecular Systems’ cobas EZH2 Mutation Test as a companion diagnostic for Tazverik.

Xpovio Approved for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
The FDA has granted accelerated approval to Karyopharm Therapeutics’ Xpovio (Selinexor) for adults with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, including diffuse large B-cell lymphoma arising from follicular lymphoma, after at least two lines of systemic therapy.

New Therapy Approved for People with Previously Treated Multiple Myeloma
The U.S. Food and Drug Administration has approved Sanofi-Aventis’s Sarclisa (isatuximab-irfc), in combination with pomalidomide and dexamethasone, for the treatment of adults with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. Sarclisa, administered through intravenous infusion, is a CD38-directed cytolytic antibody that works by helping certain cells in the immune system attack multiple myeloma cancer cells.

The FDA approved Sarclisa based on the results of a clinical trial in which study participants who received Sarclisa in combination with pomalidomide and low-dose dexamethasone showed improvement in progression-free survival with a 40-percent reduction in the risk of disease progression or death, compared to those who received pomalidomide and dexamethasone alone. These participants also had an overall response rate of 60 percent, versus 35 percent for those receiving only pomalidomide and low-dose dexamethasone.

FDA Grants Accelerated Approval to Opdivo and Yervoy Combination for Hepatocellular Carcinoma
The FDA has granted accelerated approval to the combination of Bristol-Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) for people with hepatocellular carcinoma, or HCC, who have been previously treated with sorafenib. The FDA approved this combination based on the results of a clinical trial of people with HCC whose cancer progressed after treatment with sorafenib or who did not tolerate sorafenib treatment. Thirty-three percent of trial participants receiving the combination saw their tumors destroyed or significantly reduced. Response duration ranged from 4.6 months to more than 30.5 months, with 31 percent of responses lasting at least 24 months. As this indication is approved under accelerated approval, continued approval may be contingent upon confirmatory trials.

Imfinzi Approved to Treat Extensive-Stage Small Cell Lung Cancer
AstraZeneca’s Imfinzi (durvalumab), in combination with etoposide and either carboplatin or cisplatin, has been approved by the FDA as a first-line treatment for people with extensive-stage small cell lung cancer. This approval was based on the results of a clinical trial of people with previously untreated extensive-stage small cell lung cancer which compared participants receiving Imfinzi chemotherapy to those receiving chemotherapy alone. Those receiving Imfinzi had a median overall survival of 13 months, compared with 10.3 months for those receiving just chemotherapy.

Reblozyl Approved to Treat Anemia in Adults with MDS or MPN
The FDA has approved Celgene’s Reblozyl (luspatercept-aamt) for the treatment of anemia failing an erythropoiesis stimulating agent and requiring two or more red blood cell units over eight weeks in adults with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. Reblozyl was approved based on the results of a placebo-controlled clinical trial which demonstrated that 38 percent of trial participants taking Reblozyl did not need a blood transfusion for at least eight weeks, compared with only 13 percent of those taking a placebo.

FDA Approves Braftovi in Combination with Cetuximab for Gene-Mutated Metastatic Colorectal Cancer
Array BioPharma’s Braftovi (encorafenib) in combination with cetuximab has been given FDA approval for the treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation (as detected by an FDA-approved test) after prior therapy. This approval was based on the results of a clinical trial of people with BRAF V600E mutation-positive metastatic colorectal cancer (detected by the Qiagen therascreen BRAF V600E RGQ PCR kit) with disease progression after one or two prior regimens. Trial participants receiving the Braftovi combination had a median overall survival of 8.4 months, versus 5.4 months for those in the control group, who were given either irinotecan or FOLFIRI with cetuximab.

Koselugo Gains FDA Approval as Treatment for Certain Children with Neurofibromatosis
The FDA has approved Koselugo (selumetinib) for children, two years of age and older, with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Koselugo, a kinase inhibitor marketed by AstraZeneca, is the first therapy approved for children who have this debilitating, and often disfiguring, rare disease.

FDA Approves First Therapy for Treatment of Low-Grade Upper Tract Urothelial Cancer
UroGen’s Jelmyto (mitomycin gel) has received FDA approval as the first therapy to treat low-grade upper tract urothelial cancer. Urothelial cancer is a cancer of the lining of the urinary system. While most urothelial cancers occur in the bladder, UTUC corresponds to a subset of urothelial cancers that arise in the lining of the kidney or the ureter.

“This is the first approval specifically for patients with low-grade UTUC and provides an option for some patients who may otherwise require a nephroureterectomy,” says Richard Pazdur, md, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Due to substantial treatment challenges associated with the complex anatomy of the upper urinary tract, many patients need to be treated with radical surgery – usually complete removal of the affected kidney, ureter, and bladder cuff. Jelmyto gives patients, for the first time, an alternative treatment option for low-grade UTUC.”

FDA Approves First Targeted Treatment for People with Cholangiocarcinoma
The FDA has granted accelerated approval to Incyte’s Pemazyre (pemigatinib), the first treatment approved for adults with certain types of previously treated, advanced cholangiocarcinoma, a cancer of bile ducts. Specifically, this approval is for people with cholangiocarcinoma that is locally advanced or metastatic and who have tumors that have a fusion or other rearrangement of a gene called fibroblast growth factor receptor 2.

FDA Approves First New Drug Under International Collaboration, A Treatment Option for People with HER2-Positive Metastatic Breast Cancer
As part of Project Orbis, the U.S. Food and Drug Administration has approved Tukysa (tucatinib) in
combination with chemotherapy (trastuzumab and capecitabine) for the treatment of adults with advanced forms of HER2-positive breast cancer that can’t be removed with surgery or has spread to other parts of the body, including the brain, and who have received one or more prior treatments.

Tukysa, a kinase inhibitor marketed by Seattle Genetics, is approved for treatment after people have taken one or more anti-HER2-based regimens in the metastatic setting. The FDA approved Tukysa based on the results of a clinical trial showing that participants who received Tukysa, trastuzumab, and capecitabine had a median progression-free survival of 7.8 months, compared to 5.6 months in those who received placebo, trastuzumab, and capecitabine.

Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. This new global collaboration may have an impact on the increasingly international conduct of cancer clinical trials, potentially accelerating the development of anticancer products.

FDA Approves New Therapy for Triple-Negative Breast Cancer That Has Spread, Not Responded to Other Treatments
Trodelvy (sacituzumab govitecan-hziy) has been granted accelerated approval by the FDA for the treatment of adults with triple-negative breast cancer that has spread to other parts of the body. A person must have received at least two prior therapies before taking Trodelvy.

“Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options. Chemotherapy has been the mainstay of treatment for triple-negative breast cancer. The approval of Trodelvy today represents a new targeted therapy for patients living with this aggressive malignancy,” says Richard Pazdur, md, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Trodelvy, which is marketed by Immunomedics, was granted accelerated approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. Further clinical trials are required to verify and describe Trodelvy’s clinical benefit.

Imbruvica Plus Rituximab Approved as Treatment for CLL and SLL
The FDA has expanded the indication of Pharmacyclics’s Imbruvica (ibrutinib) to include its combination with rituximab for the initial treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma. This review was conducted under Project Orbis, which provides a framework for concurrent submission and review of oncology drugs among international partners. Approval was based on a clinical trial which demonstrated a statistically significant improvement in progression-free survival for people receiving Imbruvica plus rituximab, compared with those receiving fludarabine, cyclophosphamide, and rituximab.

FDA Approves New Dosing Regimen for Keytruda
The FDA has granted accelerated approval to a new dosing regimen of 400 mg every six weeks for Merck’s Keytruda (pembrolizumab) across all currently approved adult indications, in addition to the current 200 mg every three weeks dosing regimen. As this indication is approved under accelerated approval, continued approval may be contingent upon confirmatory trials.

FDA Approves Zejula for First-Line Maintenance of Advanced Ovarian Cancer 
GlaxoSmithKline’s Zejula (niraparib) has been approved by the FDA for the maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy. This application was granted priority review.

Keytruda Approved to Treat BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer
The Food and Drug Administration has approved Merck’s Keytruda (pembrolizumab) for the treatment of people with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are ineligible for or have elected not to undergo cystectomy.

Efficacy was investigated in a multicenter, single-arm trial of 148 people with high-risk non-muscle invasive bladder cancer, 96 of whom had BCG-unresponsive carcinoma in situ with or without papillary tumors. The complete response rate in the 96 people with high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ was 41 percent, and median response duration was 16.2 months. Forty-six percent of responding participants experienced a complete response lasting at least 12 months.

FDA Approves the First Targeted Therapy to Treat a Rare Mutation in People with Gastrointestinal Stromal Tumors
The FDA had granted approval to Ayvakit (avapritinib) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. This approval includes GIST that harbors a PDGFRA D842V mutation, which is the most common exon 18 mutation. Ayvakit, which is marketed by Blueprint Medicines Corporation, is a kinase inhibitor.

“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST. However, [this] approval provides patients with the first drug specifically approved for GIST harboring this mutation,” says Richard Pazdur, md, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Clinical trials showed a high response rate with almost 85% of patients experiencing tumor shrinkage with this targeted drug.”

The FDA approved Ayvakit based on the results of a clinical trial that measured how many people experienced complete or partial shrinkage of their tumors during treatment, called overall response rate. For people harboring a PDGFRA exon 18 mutation, the overall response rate was 84 percent. For the subgroup of people with PDGFRA D842V mutations, the overall response rate was 89 percent.

First Treatment Option Specifically for People with Epithelioid Sarcoma, a Rare Soft Tissue Cancer, Gains FDA Approval
Accelerated approval has been granted to Tazverik (tazemetostat) for the treatment of adults and adolescents aged 16 years and older with metastatic or locally advanced epithelioid sarcoma. Epithelioid sarcoma is a rare sub-type of soft tissue sarcoma that often occurs in young adults.

Tazverik, which is marketed by Epizyme, blocks activity of the EZH2 methyltransferase, which may help keep the cancer cells from growing. Most cases of epithelioid sarcoma begin in the soft tissue under the skin of an extremity. However, there is a high likelihood for local and regional spread of the disease even with treatment, and approximately 50 percent of those diagnosed have metastatic disease at the time of diagnosis.

Tazverik’s approval was based on the results of a clinical trial of people with metastatic or locally advanced epithelioid sarcoma. The trial measured how many people experienced complete or partial shrinkage of their tumors during treatment, called overall response rate. The overall response rate was 15 percent, with 1.6 percent of trial participants having a complete response and 13 percent having a partial response. Of the nine people that had a response, six (67 percent) had a response lasting six months or longer.

Nerlynx Approved for Metastatic HER2-Positive Breast Cancer
The FDA has approved Puma Biotechnology’s Nerlynx (neratinib) in combination with capecitabine for adults with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.

Efficacy of Nerlynx with capecitabine was investigated in a randomized, multicenter, open-label clinical trial. The primary efficacy outcome measures were progression-free survival and overall survival. Median progression-free survival was 5.6 months for people who received Nerlynx with capecitabine, compared to 5.5 months for those receiving lapatinib with capecitabine. The progression-free survival rate at 12 months was 29 percent vs 15 percent, respectively. Median overall survival was 21 months for people receiving Nerlynx with capecitabine, compared to 18.7 months for those receiving lapatinib plus capecitabine.

Calquence Approved to Treat CLL and SLL
The U.S. Food and Drug Administration has approved AstraZeneca’s Calquence (acalabrutinib) for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review.

FDA Office of Hematology Oncology Products Renamed Office of Oncologic Diseases
The FDA office responsible for reviewing applications for new and existing cancer therapies has reorganized and been renamed as part of modernization plans approved in September 2019. The Center for Drug Evaluation and Research Office of Hematology and Oncology Products is now the Office of Oncologic Diseases. Formerly containing three clinical divisions and one nonclinical division, the office is now composed of six smaller divisions.

Richard Pazdur, MD, who joined the FDA in 1999 as director for the Division of Drug Oncology Products and became the Office of Hematology and Oncology Products Director in 2005, is the acting director of the Office of Oncologic Diseases.

“As the practice of oncology and the treatments for these life-threatening diseases have become more complex, we recognized the need to flatten the organization with additional but smaller review divisions to enable more efficient drug review,” Dr. Pazdur says. “Reorganizing the office in this manner will allow for greater stakeholder engagement in the various disease programs.”

FDA Approves New Therapy to Treat People with Relapsed and Refractory Mantle Cell Lymphoma 
The FDA has granted accelerated approval to BeiGene USA’s Brukinsa (zanubrutinib) capsules for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy.

“Mantle cell lymphoma usually responds well to initial treatment, but eventually returns or stops responding, and the cancer cells continue to grow. This is a life-threatening condition,” says Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Clinical trials showed that 84% of patients saw tumor shrinkage with this therapy. For patients whose disease relapses or becomes refractory, secondary therapies may be successful in providing another remission, and [this] approval will provide patients with another treatment option.”

FDA Approves Xtandi for Metastatic Castration-Sensitive Prostate Cancer
The FDA has approved Astellas Pharma’s Xtandi (enzalutamide) for people with metastatic castration-sensitive prostate cancer. The FDA previously approved Xtandi for people with castration-resistant prostate cancer.

FDA Approves Tecentriq Combo to Treat Certain People with Metastatic Non-Small Cell Lung Cancer
Genentech’s Tecentriq (atezolizumab) in combination with paclitaxel protein-bound and carboplatin has been approved by the U.S. Food and Drug Administration for the first-line treatment of adults with metastatic non-squamous non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations.

Efficacy was evaluated in a multicenter, randomized, open-label trial in people with stage IV non-squamous non-small cell lung cancer who had received no prior chemotherapy for metastatic disease, but could have received prior EGFR or ALK kinase inhibitor, if appropriate. The Tecentriq combination demonstrated improvements in both progression-free survival and overall survival. 

New Type of Therapy Approved to Treat Advanced Urothelial Cancer
The FDA has granted accelerated approval to Padcev (enfortumab vedotin-ejfv), a Nectin-4-directed antibody and microtubule inhibitor conjugate, meaning the drug specifically targets cancer cells – in this case, the cell adhesion molecule Nectin-4, which is highly expressed in urothelial cancers. Padcev, which is marketed by Astellas Pharma, is indicated for the treatment of adults with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy. Padcev represents a new type of therapy for people with advanced urothelial cancer whose disease has progressed on chemotherapy and immunotherapy.

FDA Approves New Treatment Option for People with HER2-Positive Breast Cancer Who Have Progressed on Available Therapies
The FDA has granted accelerated approval to Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of adults with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. Enhertu, which is marketed by Daiichi Sankyo, is a human epidermal growth factor receptor 2 (HER2)-directed antibody and topoisomerase inhibitor conjugate, meaning that the drug targets the changes in HER2 that help the cancer grow, divide, and spread, and is linked to a topoisomerase inhibitor, which is a chemical compound that is toxic to cancer cells.

“There have been many advances in the development of drugs for HER2-positive breast cancer since the introduction of Herceptin (trastuzu-mab) in 1998. The approval of Enhertu represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. 

Lynparza Approved to Treat Metastatic Pancreatic Adenocarcinoma with Certain Gene Mutations
The FDA has approved AstraZeneca’s Lynparza (olaparib) for the maintenance treatment of adults with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma, as detected by an FDA-approved test, whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.

The FDA also approved Myriad Genetic Laboratories’ BRACAnalysis CDx test as a companion diagnostic for the selection of people with pancreatic cancer for treatment with Lynparza based upon the identification of deleterious or suspected deleterious germline mutations in BRCA1 or BRCA2 genes.

Efficacy was investigated in a double-blind, placebo-controlled, multicenter trial that randomized people with gBRCAm metastatic pancreatic adenocarcinoma to receive Lynparza or placebo until disease progression or unacceptable toxicity. Median progression-free survival was 7.4 months for people who received Lynparza, compared with 3.8 months for those who received placebo. Median over-all survival for Lynparza and placebo was 18.9 months and 18.1 months, respectively.

FDA Approves Third Oncology Drug That Targets a Key Genetic Driver of Cancer, Rather Than a Specific Type of Tumor
The U.S. Food and Drug Administration has granted accelerated approval to Rozlytrek (entrectinib), a treatment for adults and adolescents whose cancers have the specific genetic defect NTRK (neurotrophic tyrosine receptor kinase) gene fusion and for whom there are no effective treatments.

This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than the location in the body where the tumor originated. The approval marks a new paradigm in the development of cancer drugs that are “tissue agnostic.” It follows the policies that the FDA developed in a guidance document released in 2018. The previous tissue agnostic indications approved by the FDA were pembrolizumab for tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in 2017 and larotrectinib for NTRK gene fusion tumors in 2018.

Rozlytrek, which is marketed by Genentech, was also approved for the treatment of adults with non-small cell lung cancer whose tumors are ROS1-positive (mutation of the ROS1 gene) and have spread to other parts of the body (or are metastatic).

Erleada Gains FDA Approval to Treat Metastatic Castration-Sensitive Prostate Cancer
Janssen Biotech’s Erleada (apalutamide) has been granted FDA approval to treat people with metastatic castration-sensitive prostate cancer. Erleada was initially approved in 2018 for people with non-metastatic castration-resistant prostate cancer.

New Treatment Approved for People with Rare Bone Marrow Disorder
The FDA has approved Impact Biomedicines’ Inrebic (fedratinib) capsules to treat adults with certain types of myelofibrosis.

“Prior to today, there was one FDA-approved drug to treat patients with myelofibrosis, a rare bone marrow disorder. Our approval today provides another option for patients,” says Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. Jakafi (ruxolitinib) was approved by the FDA for myelofibrosis in 2011.

Keytruda Plus Lenvima Combo Gains Simultaneous Approval in Australia, Canada, and U.S.
The FDA has granted accelerated approval to the combination of Merck’s Keytruda (pembrolizumab) plus Eisai’s Lenvima (lenvatinib) for the treatment of people with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review, allowing for simultaneous decisions in all three countries.

FDA Approves Darzalex for Transplant-Eligible Multiple Myeloma
The FDA has approved Janssen Biotech’s Darzalex (daratumumab) in combination with bortezomib, thalidomide, and dexamethasone to treat adults with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.

Zejula Approved as HRD-Positive Advanced Ovarian Cancer Treatment 
Tesaro’s Zejula (niraparib) has received FDA approval for the treatment of people with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status. HRD is defined by either a deleterious or suspected deleterious BRCA mutation, or genomic instability in people with disease progression greater than six months after response to the last platinum-based chemotherapy.

Darzalex Approved to Treat People with Multiple Myeloma Who Are Ineligible for Autologous Stem Cell Transplant
The U.S. Food and Drug Administration has approved Janssen Biotech’s Darzalex (daratumumab) in combination with lenalidomide and dexamethasone for people with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

Approval was based on a phase III study comparing Darzalex in combination with lenalidomide and low-dose dexamethasone to lenalidomide and low-dose dexamethasone alone. The trial demonstrated an improvement in progression-free survival in trial participants receiving Darzalex in combination with lenalidomide and low-dose dexamethasone, compared with those receiving only lenalidomide and low-dose dexamethasone. 

This application used the Real-Time Oncology Review. FDA also granted this application priority review.

FDA Grants Accelerated Approval to Xpovio for Multiple Myeloma
Karyopharm Therapeutics’ Xpovio (selinexor) in combination with dexamethasone has been granted accelerated approval to treat adults with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Efficacy was evaluated in an open-label study of 122 people with relapsed or refractory multiple myeloma who had previously received three or more anti-myeloma treatment regimens including an alkylating agent, glucocorticoids, bortezomib, carfilzomib, lenalidomide, pomalidomide, and an anti-CD38 monoclonal antibody. The approval was based on efficacy and safety in a prespecified subgroup analysis of 83 people whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab. 

As a condition of accelerated approval, further clinical trials may be required to verify and describe Xpovio’s benefit. The FDA also granted this application fast track designation and orphan drug designation. 

FDA Approves Nubeqa for Non-Metastatic Castration-Resistant Prostate Cancer
Nubeqa (darolutamide), which is marketed by Bayer HealthCare Pharmaceuticals, has been approved by the FDA for the treatment of non-metastatic castration-resistant prostate cancer.

Approval was based on a placebo-controlled clinical trial in which the primary endpoint was metastasis-free survival. The median metastasis-free survival was 40.4 months for participants treated with Nubeqa, compared with 18.4 months for those receiving placebo.

The FDA granted Nubeqa fast track designation, in addition to granting this application priority review. 

Keytruda Approved to Treat Advanced Esophageal Squamous Cell Cancer
The FDA has approved Merck’s Keytruda (pembrolizumab) for people with recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus whose tumors express PD-L1, as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy. The FDA also approved a new use for the PD-L1 IHC 22C3 pharmDx kit as a companion diagnostic device for selecting people for the above indication.

Efficacy was investigated in two clinical trials: one measuring overall survival and one measuring overall response rate and response duration. The FDA granted these applications priority review. 

FDA Approves Turalio as Treatment for Tenosynovial Giant Cell Tumor
Turalio (pexidartinib) capsules have been granted FDA approval for adults with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Turalio, which is marketed by Daiichi Sankyo, is the first systemic therapy approved for people with tenosynovial giant cell tumor.

The FDA granted Turalio breakthrough therapy and orphan drug designation, in addition to granting this application priority review. 

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