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Last month, the US Food and Drug Administration (FDA) approved four new drugs and new formulations for two, expanded the indication for three agents, declined to approve a lung cancer drug, and discontinued trials for two investigational agents.

Here’s a snapshot of what happened last month.

New Drugs

1. The FDA has approved the immune checkpoint inhibitor cosibelimab (Unloxcyt, Checkpoint Therapeutics, Inc) for adults with metastatic or locally advanced cutaneous squamous cell carcinoma who are not eligible for curative surgery or curative radiation.

Approval was based on findings from an open-label trial in 109 patients, which found an objective response rate of 47% in patients with metastatic disease and 48% in patients with locally advanced disease. Median duration of response was not reached in those with metastatic disease and was 17.7 months in those with locally advanced disease.

2. The FDA approved zenocutuzumab (Bizengri, Merus) for adults with non–small cell lung cancer (NSCLC) or pancreatic adenocarcinoma — specifically, those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a NRG1 gene fusion who progress on or after prior systemic therapy.

Findings from the open-label trial that led to approval demonstrated an overall response rate of 33% and median duration of response of 7.4 months in patients with NSCLC, and an overall response rate of 40% and median duration of response between 3.7 months and 16.6 months in those with pancreatic adenocarcinoma. The prescribing information includes a boxed warning for embryo-fetal toxicity.

3. The FDA has approved ensartinib (Ensacove, Xcovery Holdings, Inc.) for the treatment of adults with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic NSCLC who have not previously received an ALK inhibitor.

Approval for the new ALK inhibitor was based on findings from the open-label eXalt3 trial, which found patients who received ensartinib had twofold longer progression-free survival compared with those who received crizotinib, the current first-line standard-of-care.

4. The FDA has approved remestemcel-L (Ryoncil, Mesoblast Ltd), an allogeneic bone marrow-derived mesenchymal stromal cell therapy to treat steroid-refractory acute graft-vs-host disease in children aged 2 months or older. Remestemcel-L is the first mesenchymal stromal cell product approved by the FDA for any indication.

Approval was based largely on the rate and duration of response to treatment 28 days after starting. In the phase 3 trial, 30% of children (n = 16) had a complete response to treatment 28 days after receiving remestemcel-L and 41% (n = 22) had a partial response.

“Steroid-refractory acute graft-vs-host disease is a devastating condition with an extremely poor prognosis,” said Joanne Kurtzberg, MD, of Duke University Medical Center, Durham, North Carolina, who worked on the phase 3 study. The therapy “will be life saving for so many children and will have a great impact on their families.”

New or Expanded Indications

1. The FDA has approved tislelizumab (Tevimbra, BeiGene, Ltd.) alongside platinum and fluoropyrimidine-based chemotherapy for the first-line treatment of unresectable or metastatic human epidermal growth factor receptor 2–negative gastric or gastroesophageal junction adenocarcinoma in adults whose tumors express programmed death ligand 1 (≥ 1).

This marks the second approval for the agent, which was first approved in March as second-line monotherapy for certain adult patients with unresectable or metastatic esophageal squamous cell carcinoma.

The latest approval is based on results from the randomized, double-blind, placebo-controlled, phase 3 RATIONALE-305 trial, which found that the combination of tislelizumab plus chemotherapy led to a 20% reduction in the risk for death compared with placebo plus chemotherapy (hazard ratio [HR], 0.80; P = .0011). Patients in the tislelizumab group had a median overall survival of 15.0 months vs 12.9 months for those in the placebo group.

2. The FDA has expanded the approval of durvalumab (Imfinzi, AstraZeneca) to adults with limited-stage small cell lung cancer (SCLC) whose disease has not progressed after treatment with concurrent platinum-based chemotherapy and radiation therapy. The monoclonal antibody — which has been approved for other tumor types — is the first immunotherapy regimen approved in the limited-stage SCLC setting.

In the trial that led to approval, patients receiving durvalumab alone had significantly improved overall survival (HR, 0.73) and progression-free survival (HR, 0.76) compared with those receiving placebo. Median overall survival was 55.9 months with durvalumab vs 33.4 months with placebo.

3. Encorafenib (Braftovi, Array BioPharma Inc.) is now approved with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer who have a BRAF V600E mutation, as detected by an FDA-approved test. The FDA granted accelerated approval for this expanded indication based on efficacy and safety findings from the open-label BREAKWATER trial, which found an objective response rate of 61% for patients in the tislelizumab group vs 40% for those in the placebo group.

New Formulation

1. The FDA approved a subcutaneous formulation for nivolumab and hyaluronidase (Opdivo Qvantig, Bristol Myers Squibb Company) for most previously approved solid tumor nivolumab indications in adults. The indications include nivolumab and hyaluronidase monotherapy, monotherapy maintenance after completion of nivolumab plus ipilimumab (Yervoy) therapy, or the subcutaneous formulation plus chemotherapy or cabozantinib.

The approval spans cancer indications for renal cell carcinoma, melanoma, non–small cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma, esophageal carcinoma, gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

Approval for the subcutaneous injection of the combination product was based on findings from CHECKMATE-67T trial, which assessed the subcutaneous formulation vs intravenous nivolumab in patients with previously treated advanced or metastatic clear cell renal cell carcinoma.

2. The FDA has approved a new formulation of pazopanib tablets at 200 mg for advanced renal cell carcinoma and advanced soft tissue sarcoma managed with prior chemotherapy, according to a press release from the developer. The new formulation of pazopanib (Votrient) aims to improve its solubility and bioavailability, which may allow patients to receive lower doses.

Declined Approval 

The FDA has declined to approve a subcutaneous version of the NSCLC drug amivantamab (Rybrevant), drugmaker Johnson & Johnson announced .

The FDA issued a complete response letter related to observations following a standard preapproval inspection at a manufacturing facility. The agency’s issues were not related to the product formulation or the efficacy and safety data submitted for patients with epidermal growth factor–mutated NSCLC, according to the company.

The currently approved intravenous formulation of amivantamab was not impacted by this decision.

Discontinued Trials 

Merck announced that it has discontinued the development of two experimental drugs to treat NSCLC — vibostolimab and favezelimab — following failures in trials evaluating each agent alongside pembrolizumab.

Merck said it was stopping two trials of the immunotherapy vibostolimab after an analysis showed it was unlikely to succeed, as well as halting development of favezelimab after a review of the data.

“Following a careful analysis of the data, the decision has been made to discontinue development of these candidates to prioritize other ongoing programs,” said Marjorie Green, head of oncology, global clinical development at Merck’s research unit.