FDA Updates

FDA Updates

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

Ayvakit Receives Approval for Advanced Systemic Mastocytosis
The Food and Drug Administration approved Blueprint Medicine’s Ayvakit™ (avapritinib) for adult people with advanced systemic mastocytosis (AdvSM), including people with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).

Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 X 109/L.

The recommended avapritinib dose is 200 mg orally once daily for patients with AdvSM.This application was granted priority review, breakthrough designation and orphan drug designation. (June 2021)

Truseltiq Gets Accelerated Approval for Metastatic Cholangiocarcinoma
QED Therapeutics’ Truseltiq (infigratinib) receives FDA accelerated approval, a kinase inhibitor for 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.

The FDA also approved Foundation Medicine’s FoundationOne® CDx for selection of people with FGFR2 fusion or other rearrangement as a companion diagnostic device for treatment with infigratinib.

This indication is approved under accelerated approval based on the overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

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. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA) and Health Canada. The application reviews are ongoing at the other regulatory agencies.

This application was granted priority review, fast-track designation, and orphan drug designation. (May 2021)

FDA Approves First Targeted Therapy for Lung Cancer Mutation Previously Considered Resistant to Drug Therapy
The FDA approved Amgen’s Lumakras (sotorasib) as the first treatment for adults with non-small cell lung cancer whose tumors have a specific type of genetic mutation called KRAS G12C and who have received at least one prior systemic therapy. This is the first approved targeted therapy for tumors with any KRAS mutation, which accounts for approximately 25% of mutations in non-small cell lung cancers. KRAS G12C mutations represent about 13% of mutations in non-small cell lung cancers.

“KRAS mutations have long been considered resistant to drug therapy, representing a true unmet need for patients with certain types of cancer,” said Richard Pazdur, M.D., 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. “Today’s approval represents a significant step towards a future where more patients will have a personalized treatment approach.”

Lung cancer, the most common cancer type with the highest mortality, can largely be categorized by the genetic mutations that cause it. KRAS is a type of mutation in a group of genes that help regulate cell growth and division.

As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

Lumakras was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Lumakras.

The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations.

Lumakras also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada and Medicines and Healthcare products Regulatory Agency (MHRA; United Kingdom). The application reviews are ongoing at the other regulatory agencies.

Along with Lumakras, the FDA also approved the QIAGEN therascreen KRAS RGQ PCR kit and Guardant Health’s Guardant360 CDx as companion diagnostics for Lumakras today. The QIAGEN GmbH test analyzes tumor tissue and the Guardant Health, Inc. test analyzes plasma specimens to determine if Lumakras is an appropriate treatment for patients. If no mutation is detected in a plasma specimen, the patient’s tumor should be tested. (May 2021)

First Targeted Therapy for Subset of Non-Small Cell Lung Cancer Gains FDA Approval
The FDA approved Janssen’s Rybrevant (amivantamab-vmjw) as the first treatment for adults with non-small cell lung cancer whose tumors have specific types of genetic mutations: epidermal growth factor receptor (EGFR) exon 20 insertion mutations.

The FDA also approved the Guardant Health Guardant360 CDx as a companion diagnostic for Rybrevant today.

“With today’s approval, for the first time, patients with non-small cell lung cancer with EGFR exon 20 insertion mutations will have a targeted treatment option,” said Julia Beaver, MD, chief of medical oncology in the FDA’s Oncology Center of Excellence and acting deputy director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Lung cancer is the most common cancer type and the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer accounting for 80% to 85% of all lung cancers, according to the American Cancer Society. Approximately 2% to 3% of patients with non-small cell lung cancer will have EGFR exon 20 insertion mutations, which are a group of mutations on a protein that causes rapid cell growth, and consequently, helps cancer spread. EGFR exon 20 insertion mutations are the third most common type of EGFR mutation.

The FDA granted approval of Rybrevant to Janssen Pharmaceutical Companies of Johnson & Johnson.

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. For this review, the FDA collaborated with the Brazilian Health Regulatory Agency and United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies. (May 2021)

Opdiva Approved for Resected Esophageal or GEJ Cancer
Bristol-Myers Squibb’s Opdiva (nivolumab) for people with completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease who have received neoadjuvant chemoradiotherapy.

The recommended nivolumab dose for adjuvant treatment of resected esophageal or GEJ cancer is 240 mg every 2 weeks or 480 mg every 4 weeks for a total treatment duration of 1 year. Both doses are administered as 30-minute intravenous infusions.

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. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. (May 2021)

FDA Grants Accelerated Approval to Keytruda for HER2-positive Gastric Cancer
The FDA has granted accelerated approval to Merck’s Keytruda (pembrolizumab) in combination with trastuzumab, 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.

The recommended pembrolizumab dose for adult patients with locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma in combination with trastuzumab and chemotherapy is 200 mg every 3 weeks or 400 mg every 6 weeks. (May 2021)

Zynlonta Gains Accelerated Approval for Large B-cell Lymphoma
ADC Therapeutics was granted approval for Zynlonta (loncastuximab tesirine-lpyl), a CD19-directed antibody and alkylating agent conjugate, for adults with relapsed or refractory 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.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). This application was granted priority review and orphan drug designation. (Apr. 2021)

FDA Approves Immunotherapy for Endometrial Cancer with Specific Biomarker
The FDA granted accelerated approval to GlaxoSmithKline’s Jemperli (dostarlimab) for treating people with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing chemotherapy and whose cancers have a specific genetic feature known as dMMR (which contain abnormalities that affect the proper repair of DNA inside the cell), as determined by an FDA-approved test.

“Today’s approval of Jemperli is evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, M.D., 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. “This immunotherapy was specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response in this unmet medical need population.”

Endometrial cancer is the most common gynecologic malignancy in the United States and its prevalence is increasing. Approximately 75% of endometrial cancers are diagnosed at an early stage and are typically curable with surgery. However, women with advanced and recurrent endometrial cancer have limited therapeutic options following front-line standard treatment with a platinum-containing chemotherapeutic regimen. Approximately 25% to 30% of patients with advanced endometrial cancer have dMMR tumors.

Jemperli works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). Jemperli helps the body’s immune system in its fight against cancer cells by blocking this pathway.

Jemperli received Priority Review designation and Breakthrough Therapy designation for this indication. (Apr. 2021)

FDA Approves First Immunotherapy for Initial Treatment of Gastric Cancer
Bristol Myers Squibb’s Opdivo (nivolumab) was FDA approved, in combination with certain types of chemotherapy, for the initial treatment of people with advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma. This is the first FDA-approved immunotherapy for the first-line treatment of gastric cancer.

“Today’s approval is the first treatment in more than a decade to show a survival benefit for patients with advanced or metastatic gastric cancer who are being treated for the first time,” 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.

Opdivo received Priority Review and Orphan Drug designations for this indication. Priority Review designation directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications. Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

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. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. (Apr. 2021)

Trodelvy Granted Accelerated Approval for Advanced Urothelial Cancer
The FDA granted accelerated approval to Immunomedica’s Trodelvy (sacituzumab govitecan) for people with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. This application was granted priority review and fast track designation. (Apr. 2021)

FDA Grants Regular Approval to Trodelvy for Triple-Negative Breast Cancer
Immunomedic’s Trodelvy (sacituzumab govitecan) received regular FDA approval for people with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.

In April 2020, sacituzumab govitecan received accelerated approval for people with mTNBC who have received at least two prior therapies for metastatic disease. The following trial was the confirmatory trial for the accelerated approval. This application was granted priority review and breakthrough designation. Apr. 2021)

FDA Approves New Dosing Regimen for Erbitux
The FDA approved a new dosage regimen of 500 mg/m2 as a 120-minute intravenous infusion every two weeks (Q2W) for ImClone’s Erbitux (cetuximab) for people with K-Ras wild-type, EGFR-expressing colorectal cancer (mCRC) or squamous cell carcinoma of the head and neck (SCCHN).

This approval provides for a biweekly dosage regimen option in addition to the previously approved weekly dosage regimen for the approved indications when cetuximab is used as a single agent or in combination with chemotherapy. (Apr. 2021)

Sarclisa Approved for Multiple Myeloma
The FDA approved Sanofi-Aventis’ Sarclisa (isatuximab-irfc), in combination with carfilzomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.

The recommended isatuximab-irfc dose with carfilzomib and dexamethasone is 10 mg/kg as an intravenous infusion every week for 4 weeks followed by every 2 weeks until disease progression or unacceptable toxicity. Sarclisa has orphan drug designation for the treatment of multiple myeloma. (Mar. 2021)

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FDA Approves First Cell-Based Gene Therapy for Adults with Multiple Myeloma
The FDA granted approval of Abecma (idecabtagene vicleucel), a cell-based gene therapy to treat adults with multiple myeloma who have not responded to, or whose disease has returned after, at least four prior lines (different types) of therapy, to Celgene Corporation, a Bristol Myers Squibb company. Abecma is the first cell-based gene therapy approved by the FDA for the treatment of multiple myeloma.

“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer,” says Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.

The FDA is requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Abecma. Abecma was granted Orphan Drug and Breakthrough Therapy designations by the FDA. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases. Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). Breakthrough Therapy designation was granted based on sustained responses observed in patients with relapsed and refractory myeloma. (Mar. 2021)

Keytruda approved for esophageal or GEJ carcinoma
The FDA has approved Merck’s Keytruda (pembrolizumab) in combination with platinum and fluoropyrimidine-based chemotherapy for people with metastatic or locally advanced esophageal or gastroesophageal (GEJ) (tumors with epicenter 1 to 5 centimeters above the gastroesophageal junction) carcinoma who are not candidates for surgical resection or definitive chemoradiation.

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. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. This application was granted priority review. (Mar. 2021)

FDA Approves Lorbrena for Metastatic ALK-Positive Non-Small Cell Lung Cancer
The FDA has granted regular approval to Pfizer’s Lorbrena (lorlatinib) for the treatment of people with metastatic non-small cell lung cancer whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test. The FDA also approved Ventana Medical Systems’ Ventana ALK (D5F3) CDx Assay as a companion diagnostic for Lorbrena.

Lorbrena previously received accelerated approval in November 2018 for the second- or third-line treatment of ALK-positive metastatic non-small cell lung cancer. This expanded approval of Lorbrena is based on the results from a Phase III trial, which showed a 72-percent reduction in risk of progression or death versus crizotinib in a previously untreated patient population. (Mar. 2021) 

FDA Grants Accelerated Approval to Yescarta for Relapsed or Refractory Follicular Lymphoma
Yescarta (axicabtagene ciloleucel) has gained FDA approval to treat adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Yescarta is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy manufactured by Kite Pharma. This accelerated approval was based on a single-arm, open-label, multicenter trial in which 91 percent of people with relapsed or refractory follicular lymphoma responded to Yescarta. (Mar. 2021) 

Fotivda Approved to Treat Relapsed or Refractory Advanced Renal Cell Carcinoma
The FDA has approved AVEO Pharmaceuticals’ Fotivda (tivozanib), a kinase inhibitor, for adults with relapsed or refractory advanced renal cell carcinoma following two or more prior systemic therapies.

The approval of Fotivda is based on a Phase III study comparing Fotivda to sorafenib in relapsed or refractory advanced renal cell carcinoma following two or more prior systemic therapies. The main efficacy outcome measure was progression-free survival. Median progression-free survival was 5.6 months in the Fotivda arm, compared with 3.9 months for those treated with sorafenib. Median overall survival was 16.4 and 19.2 months for the Fotivda and sorafenib arms, respectively. The objective response rate was 18 percent for the Fotivda arm and 8 percent for the sorafenib arm. (Mar. 2021) 

FDA Grants Accelerated Approval to Tepmetko for Metastatic Non-Small Cell Lung Cancer
EMD Serono’s Tepmetko (tepotinib) has received FDA approval to treat adults with metastatic non-small cell lung cancer harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (Feb. 2021) 

Ukoniq Granted Accelerated Approval to Treat Marginal Zone Lymphoma and Follicular Lymphoma
The FDA has granted accelerated approval to TG Therapeutics’ Ukoniq (umbralisib), a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon, for the following indications:

  • Adults with relapsed or refractory marginal zone lymphoma who have received at least one prior anti-CD20-based regimen
  • Adults with relapsed or refractory follicular lymphoma who have received at least three prior lines of systemic therapy

Accelerated approval was granted for these indications based on overall response rate data from a Phase II trial. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial. (Feb. 2021) 

Libtayo Approved to Treat Locally Advanced and Metastatic Basal Cell Carcinoma
Regeneron Pharmaceuticals’ Libtayo (cemiplimab-rwlc) has been approved by the FDA to treat people with locally advanced basal cell carcinoma previously treated with a hedgehog pathway inhibitor, or for whom a hedgehog pathway inhibitor is not appropriate. The FDA also granted Libtayo accelerated approval to treat people with metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor, or for whom a hedgehog pathway inhibitor is not appropriate. (Feb. 2021) 

FDA Approves New Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy
The FDA has approved Cosela (trilaciclib) as the first therapy in its class to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving certain types of chemotherapy for extensive-stage small cell lung cancer. Cosela, which is manufactured by G1 Therapeutics, may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin-dependent kinase 4/6, a type of enzyme.

“For patients with extensive-stage small cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” says Albert Deisseroth, md, phd, supervisory medical officer in the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research.

The effectiveness of Cosela was evaluated in three randomized, double-blind, placebo-controlled studies in people with extensive-stage small cell lung cancer. Combined, these studies randomly assigned 245 people to receive either an infusion of Cosela in their veins or a placebo before chemotherapy. The studies then compared the two groups for the proportion of patients with severe neutropenia and the duration of severe neutropenia in the first cycle of chemotherapy. In all three studies, trial participants who received Cosela had a lower chance of having severe neutropenia compared to those who received a placebo. Among those who had severe neutropenia, people who received Cosela, on average, had it for a shorter time than those who received a placebo. (Feb. 2021) 

FDA Approves Libtayo for Non-Small Cell Lung Cancer with High PD-L1 Expression
Regeneron Pharmaceuticals’ PD-1 inhibitor Libtayo (cemiplimab-rwlc) has received FDA approval as a first-line treatment of people with locally advanced non-small cell lung cancer whose tumors have high PD-L1 expression, as determined by an FDA-approved test. Eligible non-small cell lung cancer survivors must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation, and the tumors must not have EGFR, ALK, or ROS1 aberrations.

This approval was based on an analysis of 710 people with locally advanced non-small cell lung cancer who were not candidates for surgical resection or definitive chemoradiation, or with metastatic non-small cell lung cancer, who were randomized to receive treatment in a Phase III trial. Eligible participants were intended to have PD-L1 expression of ≥50%. In this population, Libtayo reduced the risk of death by 32 percent compared to chemotherapy. (Feb. 2021) 

Pepaxto Combination Receives Accelerated Approval for Relapsed or Refractory Multiple Myeloma
The FDA has granted accelerated approval to Oncopeptides’ Pepaxto (melphalan flufenamide), in combination with dexamethasone, for adults with relapsed or refractory multiple myeloma 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.

This indication has been granted under accelerated approval based upon a clinical trial evaluating intravenous Pepaxto in combination with dexamethasone, which included heavily pre-treated patients with a poor prognosis. The study looked at 157 people with relapsed or refractory multiple myeloma, of whom 97 were triple-class refractory and had received at least four prior lines of treatment. The overall response rate for those within this group of people with refractory multiple myeloma was 23.7 percent and the median duration of response was 4.2 months.

Pepaxto was approved under accelerated approval, which allows for earlier approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. (Feb. 2021) 

New Treatment Approved for Adults with Relapsed or Refractory Large-B-Cell Lymphoma
The U.S. Food and Drug Administration has approved Juno Therapeutics’ Breyanzi (lisocabtagene maraleucel), a cell-based gene therapy, to treat adults with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least two other types of systemic treatment. Breyanzi is a chimeric antigen receptor (CAR) T-cell therapy that uses a person’s own T-cells to help fight the lymphoma.

The safety and efficacy of Breyanzi were established in a multicenter clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54 percent. Breyanzi is not indicated for the treatment of people with primary central nervous system lymphoma. (Jan. 2021) 

FDA Approves Enhertu for HER2-Positive Gastric Adenocarcinomas
The FDA has approved Daiichi Sankyo’s Enhertu (fam-trastuzumab deruxtecan-nxki) for adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal adenocarcinoma who have received a prior trastuzumab-based regimen. Approval was based on the positive results of a Phase II trial in which Enhertu demonstrated a statistically significant and clinically meaningful improvement in both overall survival and objective response rate versus chemotherapy (irinotecan or paclitaxel) in people with advanced gastric cancer or gastroesophageal adenocarcinoma who had progressed on at least two or more prior regimens, including trastuzumab plus a fluoropyrimidine- and platinum-based chemotherapy combination. (Jan. 2021) 

Opdivo Plus Cabometyx Combination Gains FDA Approval for the Treatment of Advanced Renal Cell Carcinoma
The combination of Bristol-Myers Squibb’s Opdivo (nivolumab) and Exelixis’s Cabometyx (cabozantinib) has been cleared by the FDA as a first-line treatment for people with advanced renal cell carcinoma. Approval was based on Phase III trial results which demonstrated that the Opdivo plus Cabometyx combination doubled median progression-free survival and objective response rate and showed superior overall survival versus sunitinib in people with previously untreated advanced renal cell carcinoma. (Jan. 2021) 

FDA Approves Xalkori for Children and Young Adults with Relapsed or Refractory, Systemic Anaplastic Large Cell Lymphoma
The FDA has approved Pfizer’s Xalkori (crizotinib) for children, one year of age and older, and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma that is ALK-positive. The safety and efficacy of Xalkori have not been established in older adults with relapsed or refractory, systemic ALK-positive anaplastic large cell lymphoma.

The FDA approval is based on results from a multicenter study of 121 participants between the ages of 1 and 21, which included 26 people with relapsed or refractory, systemic ALK-positive anaplastic large cell lymphoma after at least one systemic treatment. Treatment with Xalkori resulted in an objective response rate of 88 percent. Among the 23 study participants who achieved a response, 39 percent maintained their response for at least 6 months, and 22 percent maintained their response for at least 12 months. (Jan. 2021) 

Darzalex Faspro Granted Accelerated Approval to Treat Newly Diagnosed Light Chain Amyloidosis
The FDA has granted accelerated approval to Janssen Biotech’s Darzalex Faspro (daratumumab plus hyaluronidase) in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed light chain amyloidosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

This approval is based on positive results from a Phase III study that evaluated Darzalex Faspro in combination with bortezomib, cyclophosphamide, and dexamethasone, compared with bortezomib, cyclophosphamide, and dexamethasone alone, a common treatment regimen used in adults with newly diagnosed light chain amyloidosis. Trial participants receiving treatment with Darzalex Faspro experienced a hematologic complete response rate more than triple that of those receiving bortezomib, cyclophosphamide, and dexamethasone alone. (Jan. 2021) 

FDA Grants Accelerated Approval to Keytruda for Locally Recurrent Unresectable or Metastatic Triple-Negative Breast Cancer
The U.S. Food and Drug Administration has granted accelerated approval to Merck’s Keytruda (pembrolizumab), in combination with chemotherapy, for the treatment of people with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 as determined by an FDA-approved test. This application was granted accelerated approval based on progression-free survival. The FDA also approved Dako North America’s PD-L1 IHC 22C3 pharmDx as a companion diagnostic for selecting people with triple-negative breast cancer for Keytruda.

Danyelza Granted Accelerated Approval for High-Risk Neuroblastoma in Bone or Bone Marrow
The FDA has granted accelerated approval to Y-mAbs Therapeutics’ Danyelza (naxitamab), in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for children, one year of age and older, and adults with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow that has demonstrated a partial response, minor response, or stable disease to prior therapy. This application was granted accelerated approval based on overall response rate and duration of response.

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FDA Approves New Device to Treat Osteoid Osteoma in the Extremities
Profound Medical’s Sonalleve MR-HIFU system has received FDA approval for the treatment of osteoid osteoma in the extremities. MR-guided High Intensity Focused Ultrasound (MR-HIFU) treatment is an image-guided technique combining high-intensity focused ultrasound ablation with real-time monitoring of temperature change during the sonication.

Gavreto Approved to Treat RET-Altered Thyroid Cancers
The FDA has approved Blueprint Medicines’ Gavreto (pralsetinib) for adults and children 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, or with RET fusion-positive thyroid cancer who require systemic therapy, and who are radioactive iodine-refractory (if radioactive iodine is appropriate). This application was granted accelerated approval based on overall response rate and duration of response.

FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer
The FDA has approved Gallium 68 PSMA-11 – the first drug for PET imaging of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer. Gallium 68 PSMA-11 is indicated for people with suspected prostate cancer metastasis that is potentially curable by surgery or radiation therapy. Gallium 68 PSMA-11 is also indicated for people with suspected prostate cancer recurrence based on elevated serum PSA levels. Gallium 68 PSMA-11 is a radioactive diagnostic agent that is administered in the form of an intravenous injection. The FDA granted this approval to the University of California, Los Angeles, and the University of California, San Francisco.

Margenza Approved for Metastatic HER2-Positive Breast Cancer
The U.S. Food and Drug Administration approved MacroGenics’ Margenza (margetuximab-cmkb), in combination with chemotherapy, for the treatment of adults with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

Xpovio Gains Approval for Refractory or Relapsed Multiple Myeloma
The FDA has approved Karyopharm Therapeutics’ Xpovio (selinexor), in combination with bortezomib and dexamethasone, for the treatment of adults with multiple myeloma who have received at least one prior therapy. The FDA previously granted Xpovio accelerated approval in 2019, in combination with dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma who 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.

FDA Approves First Oral Hormone Therapy for Treating Advanced Prostate Cancer
The FDA has approved Myovant Sciences’ Orgovyx (relugolix) for the treatment of adults with advanced prostate cancer. One of the treatment options for advanced prostate cancer is androgen deprivation therapy, which uses drugs to lower levels of the hormones that help prostate cancer cells grow. Current FDA-approved treatments of this type are injected or placed as small implants under the skin. Orgovyx is an orally administered treatment that works by blocking the pituitary gland from making hormones called luteinizing hormone and follicle-stimulating hormone, thereby reducing the amount of testosterone the testicles are able to make. “[This] approval marks the first oral drug in this class, and it may eliminate some patients’ need to visit the clinic for treatments that require administration by a healthcare provider,” 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.

First Adjuvant Therapy for Most Common Type of Lung Cancer Receives FDA Approval
The FDA has approved AstraZeneca’s Tagrisso (osimertinib) as the first adjuvant treatment for people with non-small cell lung cancer whose tumors have an epidermal growth factor receptor (EGFR) mutation. Tagrisso previously was approved in 2018 for the first-line treatment of people with metastatic non-small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.

“[This] approval of Tagrisso demonstrates how additional research on therapies approved in later stages of cancer can eventually improve treatment options for patients in earlier stages,” says Richard Pazdur, MD. “With this approval, patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer.”

FDA Approves Supplemental New Drug Application for Iclusig as Treatment for Resistant or Intolerant Chronic-Phase CML
The FDA has approved the supplemental New Drug Application for Takeda’s Iclusig (ponatinib) for adults with chronic phase chronic myeloid leukemia with resistance or intolerance to at least two prior kinase inhibitors. The updated label includes an optimized, response-based dosing regimen which aims to maximize the benefit-risk ratio by providing efficacy and decreasing the risk of adverse events.

“CML can be difficult to treat, particularly when patients have experienced resistance or intolerance to two or more [tyrosine kinase inhibitors]. The revised indication allows physicians to consider Iclusig earlier in a course of treatment for chronic phase CML patients, when it might provide the potential for the greatest benefit,” says Jorge Cortes, MD, director of the Georgia Cancer Center.

FDA Announces First of Its Kind Pilot Program to Communicate Patient-Reported Outcomes from Cancer Clinical Trials
The U.S. Food and Drug Administration has launched Project Patient Voice, an initiative of the FDA’s Oncology Center of Excellence. Through a new website, Project Patient Voice creates a consistent source of publicly available information describing patient-reported symptoms from cancer trials for marketed treatments. While this patient-reported data has historically been analyzed by the FDA during the drug approval process, it is rarely included in product labeling and, therefore, is largely in-accessible to the public.

Patient-reported data can provide additional, complementary information for healthcare professionals to discuss with people facing cancer, specifically when discussing the potential side effects of a particular cancer treatment. In contrast to the clinician-reported safety data in product labeling, the data in Project Patient Voice is obtained directly from cancer survivors and can show symptoms before treatment starts and at multiple time points while receiving cancer treatment. 

Keytruda Approved to Treat Cutaneous Squamous Cell Carcinoma
The FDA has approved Merck’s Keytruda (pembrolizumab) for people with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation. This approval was based on data from a Phase II trial in which Keytruda demonstrated meaningful efficacy and durability of response, with an objective response rate of 34 percent. 

Inqovi Oral Combination Gains FDA Approval for the Treatment of Myelodysplastic Syndromes
The FDA has approved an oral combination of decitabine and cedazuridine – Inqovi (manufactured by Astex) – for adults with myelodysplastic syndromes, including the following:

  • previously treated and untreated de novo and secondary MDS with the following subtypes: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia 
  • intermediate-1, intermediate-2,and high-risk International Prognostic Scoring System groups.

FDA Approves New Breast Cancer Treatment That Can Be Administered at Home by Healthcare Professional
Phesgo – a combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf – has been approved for injection under the skin to treat adults with HER2-positive breast cancer that has spread to other parts of the body, and for treatment of adults with early HER2-positive breast cancer. Phesgo, which is manufactured by Genentech, is initially used in combination with chemotherapy and could continue to be administered at home by a qualified healthcare professional once the chemotherapy regimen is finished.

“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, Phesgo offers an outpatient option for patients to receive trastuzumab and pertuzumab,” 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.

Eligible breast cancer survivors should be selected based on an FDA-approved companion diagnostic test.

First-Line Immunotherapy for People with Certain Types of Metastatic Colorectal Cancer Gains FDA Approval
The FDA has approved Merck’s Keytruda (pembrolizumab) for intravenous injection for the first-line treatment of people with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. This marks the first immunotherapy approved for this group of people as a first-line treatment and which is administered without also giving chemotherapy.

“Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis. Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity,” 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. “Having a non-chemotherapy option available for selected patients is a noteworthy paradigm shift in treatment.”

Keytruda works by targeting the cellular pathway of proteins found on the body’s immune cells and some cancer cells, known as PD-1/PD-L1. By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells and provide a benefit in people with MSI-H or dMMR metastatic colorectal cancer. The FDA previously approved Keytruda to treat other types of cancer.

FDA Approves Bavencio for Urothelial Carcinoma Maintenance Treatment
EMD Serono’s Bavencio (avelumab) has been granted FDA approval for maintenance treatment of people with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

The approval is based on results from a Phase III trial that demonstrated a significant 7.1-month improvement in median overall survival with Bavencio as first-line maintenance plus best supportive care, compared with best supportive care alone. This statistically significant improvement in overall survival represents a 31-percent reduction in the risk of death in the overall population. The results from this study supported the conversion of accelerated approval of Bavencio to a regular approval.

FDA Approves First Cell-Based Gene Therapy for Adults with Relapsed or Refractory Mantle Cell Lymphoma 
The FDA has approved Tecartus (brexucabtagene autoleucel), a cell-based gene therapy for the treatment of adults diagnosed with mantle cell lymphoma who have not responded to or who have relapsed following other kinds of treatment. Tecartus, a chimeric antigen receptor (CAR) T cell therapy manufactured by Kite Pharma, is the first cell-based gene therapy approved by the FDA for the treatment of mantle cell lymphoma.

Each dose of Tecartus is a customized treatment created using a person’s own immune system to help fight the lymphoma. The person’s T cells, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells. These modified T cells are then infused back into the person receiving treatment.

Tecentriq Combo Approved for BRAF V600 Unresectable or Metastatic Melanoma
Genentech’s Tecentriq (atezolizumab), in combination with cobimetinib and vemurafenib, has been granted FDA approval to treat people with BRAF V600 mutation-positive unresectable or metastatic melanoma. This approval is based on results from a Phase III trial in which the addition of Tecentriq to cobimetinib and vemurafenib helped people live longer without their disease worsening or death, compared to placebo plus cobimetinib and vemurafenib. 

FDA Grants Accelerated Approval to Monjuvi as Treatment for Diffuse Large B-cell Lymphoma
The FDA has granted accelerated approval to Monjuvi (tafasitamab-cxix), indicated in combination with lenalidomide, for adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (including diffuse large B-cell lymphoma arising from low grade lymphoma) and who are not eligible for autologous stem cell transplant. Monjuvi, which is manufactured by MorphoSys US, is a CD19-directed cytolytic antibody. 

Blenrep Granted Accelerated Approval to Treat Multiple Myeloma
GlaxoSmithKline’s Blenrep (belantamab mafodotin-blmf) has been given FDA approval to treat adults with relapsed or refractory multiple myeloma who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

FDA Approves Kyprolis and Darzalex with Dexamethasone to Treat Multiple Myeloma
The FDA has approved Onyx Pharmaceuticals’ Kyprolis (carfilzomib) and Janssen Biotech’s Darzalex (daratumumab), in combination with dexamethasone, for adults with relapsed or refractory multiple myeloma who have received one to three lines of therapy. The efficacy of this combination was demonstrated in a Phase III trial which showed a 37-percent reduction in the risk of disease progression or death in people receiving Kyprolis and Darzalex plus dexamethasone, compared to Kyprolis and dexamethasone alone. 

FDA Approves Onureg as Treatment for Acute Myeloid Leukemia
The FDA has approved Celgene’s Onureg (azacitidine tablets) for continued treatment of people with acute myeloid leukemia who achieved first complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and who are not able to complete intensive curative therapy.

Approval for this indication was based on a Phase III placebo-controlled trial which showed a statistically significant improvement in overall survival for people treated with Onureg – a median overall survival of 24.7 months for those being treated with Onureg, compared with 14.8 months for those given a placebo. 

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