Amgen gets a full approval for Imdelltra

Six months after releasing the Dellphi-304 results, Amgen has secured full approval for its DLL3-targeting T-cell engager Imdelltra in second-line small-cell lung cancer, a development with important implications for Zai Lab.

Zai is chasing an accelerated approval for zocilurtatug pelitecan, its DLL3-targeting ADC, but in October revealed that its phase 3 trial would be delayed; as of Thursday this study was still not enrolling patients, according to clinicaltrials.gov. The key uncertainty now is whether an accelerated pathway remains open with a fully approved competing drug already on the market.

Zai's delay was caused by increasing the trial's sample size to account for including Imdelltra in the control arm. The study carries co-primary endpoints of ORR and OS, and the first will presumably be used to support an accelerated approval filing.

For Amgen, Imdelltra's pivotal trial delivered a clear survival win, showing median overall survival of 13.6 months versus 8.3 months for chemotherapy. Importantly, the safety profile seemed to be better than in other trials, with only 1% grade 3 CRS events and none at grade 4 or 5; still, the label carries a boxed warning for cytokine release syndrome and ICANS.

Zocilurtag pelitecan

At the Triple (EORTC-NCI-AACR) meeting Zai Lab reported updated phase 1 results showing a 68% ORR, including confirmed and unconfirmed responses, among 19 second-line patients treated with a 1.6mg/kg zoci-P dose. 

This marked a decline from the 79% ORR previously reported among 14 patients in the same cohort. Still, in a cross-trial comparison the response rates remain higher than those achieved by Imdelltra, but Imdelltra's full approval now causes Zai some significant problems. 

The cautionary tale here is the 2021 filing of Agenus's balstilimab for second-line cervical cancer on the back of an uncontrolled trial, a plan that unravelled when Merck & Co's Keytruda secured full approval, resulting in this filing being pulled. One difference is that Zai's upcoming phase 3 study is controlled, and it will ultimately be up to the FDA to determine how much data is needed to back a filing.

Meanwhile, Amgen is moving into earlier lines of treatment. Multiple front-line programmes are under way including Dellphi-312, which started in August, and two trials evaluating Imdelltra as a maintenance treatment in both extensive-stage and limited-stage SCLC, expected to be completed in 2027 and 2030 respectively. 

Additionally, the company is evaluating a subcutaneous formulation of the molecule in a phase 1 trial that is expected to read out in 2027.

Selected trials of Imdelltra

Source: OncologyPipeline.