Oncology in December 2024 – FDA Cancer News Roundup

Last month, the US Food and Drug Administration (FDA) approved four new drugs and two new formulations, added new indications for three agents, rejected a lung cancer drug, and abandoned clinical trials involving two experimental agents.

Newly Approved Drugs

1. Cosibelimab (Unloxcyt, Checkpoint Therapeutics, Inc): The FDA approved cosibelimab for patients with metastatic or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiotherapy.

   • Clinical Findings: In an open-label study involving 109 patients, the objective response rate was 47% in patients with metastatic disease and 48% in those with locally advanced disease.

   • Response Duration: Median response duration was not reached in patients with metastatic disease and was 17.7 months in those with locally advanced disease.

2. Zenocutuzumab (Bizengri, Merus): The FDA approved zenocutuzumab for patients with advanced, unresectable, or metastatic NRG1 gene fusion -positive disease resistant to systemic therapy, including non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma.

   • Clinical Findings: In patients with NSCLC, the overall response rate was 33% and median response duration was 7.4 months. In patients with pancreatic cancer, the response rate was 40%, with median response durations ranging from 3.7 to 16.6 months.

   • Warning: The drug's prescribing information includes a boxed warning highlighting embryo-fetal toxicity.

3. Ensartinib (Ensacove, Xcovery Holdings, Inc.): Ensartinib was approved for patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic NSCLC.

   • Clinical Findings: According to data from the open-label eXalt3 study, progression-free survival in patients receiving ensartinib was twice as long as in those receiving crizotinib, the current standard treatment: 25.8 months versus 12.7 months.

4. Remestemcel-L (Ryoncil, Mesoblast Ltd): The FDA approved remestemcel-L for pediatric patients older than 2 months with corticosteroid-refractory acute graft-versus-host disease. This is the first mesenchymal stromal cell therapy approved by the FDA for any indication.

   • Clinical Findings: In a phase 3 study, 30% of patients had a complete response and 41% had a partial response by day 28 after treatment began.

   • Expert Commentary: Dr. Joanne Kurtzberg said this treatment would be a "lifesaver" for children and their families.

New or Expanded Indications

1. Tislelizumab (Tevimbra, BeiGene, Ltd.): The FDA approved the anti-PD-1 immunotherapy drug tislelizumab, together with platinum- and fluoropyrimidine-based chemotherapy, for patients with HER2-negative gastric or gastroesophageal junction adenocarcinoma .

   • Clinical Findings: In the phase 3 RATIONALE-305 study, tislelizumab plus chemotherapy reduced the risk of death by 20% compared with placebo plus chemotherapy (HR: 0.80; P = 0.0011). Median overall survival was 15 months in the tislelizumab group and 12.9 months in the placebo group.

2. Durvalumab (Imfinzi, AstraZeneca): The FDA approved durvalumab for patients with limited-stage small cell lung cancer (SCLC) whose disease had not progressed after receiving platinum-based chemotherapy and radiotherapy.

   • Clinical Findings: In a phase 3 study, median overall survival was 55.9 months in patients receiving durvalumab and 33.4 months in the placebo group (HR: 0.73).

3. Encorafenib (Braftovi, Array BioPharma Inc.): The FDA expanded the use of encorafenib in combination with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer with a BRAF V600E mutation.

   • Clinical Findings: In the BREAKWATER study, the objective response rate was reported as 61% in the encorafenib group and 40% in the placebo group.

New Formulations

1. Nivolumab and Hyaluronidase (Opdivo Qvantig, Bristol Myers Squibb Company): The FDA approved a subcutaneous formulation of nivolumab for most solid tumor indications.

   • Scope: Many cancer types, including renal cell carcinoma, melanoma, NSCLC, head and neck squamous cell carcinoma, and hepatocellular carcinoma.

   • Clinical Findings: In the CHECKMATE-67T study, subcutaneous injection showed efficacy similar to intravenous administration.

2. Pazopanib (Votrient): The FDA approved a new 200 mg pazopanib tablet formulation for advanced renal cell carcinoma and chemotherapy-treated soft tissue sarcomas.

   • Aim: The new formulation may enable treatment at lower doses by improving solubility and bioavailability.

Rejected Approval

The FDA rejected approval of the subcutaneous formulation of amivantamab (Rybrevant) , which was developed for the treatment of non-small cell lung cancer (NSCLC).

• Reason: The rejection concerned inspection findings at the manufacturing facility, rather than the product formulation or clinical efficacy.

• Impact: The existing intravenous formulation was not affected.

Discontinued Clinical Trials

Merck discontinued development of the experimental drugs vibostolimab and favezelimab for NSCLC.

• Reason: Interim analyses of studies combining these agents with pembrolizumab found that the expected efficacy would not be achieved.

• Statement: Merck stated that resources would be redirected to other ongoing projects.

These developments highlight both promising innovations in cancer treatment and treatment strategies that have not succeeded. FDA approvals continue to help us better define patient selection criteria and closely follow advances in cancer care.