FDA red and green lights: March 2025

Of three potentially controversial FDA decisions made in March, the agency erred on the side of lenience, granting green lights to Novartis’s radiopharmaceutical Pluvicto and Exelixis’s kinase inhibitor Cabometyx in new indications.

However, it wasn’t so generous to Jiangsu HengRui and Elevar’s camrelizumab and rivoceranib combo, which got its second complete response letter within a year.

The companies had hoped to get the PD-1 and VEGF inhibitors approved in first-line liver cancer, based on the Cares-310 trial. However, the FDA had other ideas. The May 2024 CRL cited manufacturing issues, but the exact reasons for the latest rejection are unclear.

Cabinet

It was better news for Exelixis, which got approval for Cabometyx in previously treated neuroendocrine tumours, despite doubts about the Cabinet study on which the filing was based. Although the trial showed a benefit on progression-free survival it didn’t meet a key secondary endpoint of overall survival.

Cabinet might have been confounded by a high rate of crossover and treatment with subsequent therapies, but some saw even more fundamental issues, with Professor Vinay Prasad, a frequent critic of the industry, questioning why placebo was used rather than an active control, particularly as some patients hadn’t received Novartis’s Lutathera, or Afinitor, or even chemo. Still, these questions clearly didn’t trouble the FDA.

And the agency was also generous towards Pluvicto, granting approval in metastatic castration-resistant prostate cancer after androgen therapy, but before chemo, adding to an existing post-chemo use. There was similarly no overall survival benefit in the PSMAfore study, although this endpoint, though extremely high crossover rates won't have helped. Novartis reckons the latest nod will triple the number of patients eligible for Pluvicto.

PD-(L)1 nods

March’s other three oncology approvals all came in the PD-1 space, the most notable of which was for BeiGene’s Tevimbra in oesophageal squamous cell carcinoma. 

The company had been awaiting a decision since last July, having also been scuppered by a delay in clinical site inspections. As expected, following an adcom in September, Tevimbra only got the nod in patients expressing PD-L1 at 1% or higher; still, this is better than in the EU, where it’s only indicated for patients with PD-L1 ≥5%.

A similar fate befell Keytruda, whose March full approval in first-line gastric cancer was limited to PD-L1 ≥1%; however, this had been expected after the FDA limited its accelerated approval for this use to this population.

Finally, AstraZeneca’s Imfinzi got the green light in perioperative muscle-invasive bladder cancer, an area of increasing activity.

Selected March 2025 US regulatory decisions in oncology

Note: ARPI=androgen receptor pathway inhibitor; CRPC=castrate-resistant prostate cancer; epNET=extra-pancreatic neuroendocrine tumour; pNET=pancreatic neuroendocrine tumour. Source: OncologyPipeline.