Amgen pads Imdelltra's case in tough-to-treat lung cancer subtype with phase 3 survival win

 Nearly a year after winning an accelerated approval for its DLL3-targeting small cell lung cancer (SCLC) therapy Imdelltra, Amgen is further proving the drug's worth with overall survival data from an interim analysis of a phase 3 study. 

Topline results proved that Imdelltra use resulted in “statistically significant and clinically meaningful” improvement in overall survival compared with local standard-of-care chemotherapy across patients with SCLC whose disease progressed after one line of platinum-based chemotherapy, Amgen reported.

The findings demonstrate “overwhelming clinical benefit for people living with this devastating disease and affirm Imdelltra as standard of care," Amgen’s Executive Vice President of R&D Jay Bradner, M.D., noted in a statement. “We look forward to sharing these results with the scientific community and health authorities as we continue our efforts to bring Imdelltra to patients worldwide."

The data could potentially be used to support a full approval for Imdelltra. The FDA blessed the drug with an accelerated approval in extensive-stage SCLC ahead of schedule last May based on a phase 2 trial in which Imdelltra reduced tumors in 40% of SCLC patients who had failed on two prior lines of treatment and proved a median duration of response of 9.7 months. The nod made the drug the first FDA-approved bispecific T-cell engager cleared to treat the disease. 

Those phase 2 results represented a “watershed moment” for Amgen’s oncology team, chief medical officer Paul Burton, M.D., told Fierce Biotech in 2023.

“This represents about a tripling of the duration of survival,” Burton said at the time.

SCLC is a tough-to-treat and aggressive lung cancer subtype that has a 5% to 10% five-year relative survival rate across all stages combined. While patients typically have high initial response rates to first-line platinum-based chemotherapy, most quickly relapse within a few months, according to Amgen.

While the phase 2 data was enough to snag an accelerated approval, there was a bit of a safety concern with Amgen’s initial drug approval application. As it turns out, nearly 400 adverse events were not reported in the original application, an FDA review document revealed a few months after the approval. Amgen later conducted a sweeping review of its trial sites and was able to add the missing safety events to the drug’s application midway through the FDA’s review process. 

The “large number” of underreported events was a “major concern” to FDA reviewers, but the agency ultimately decided that Amgen’s source data verification for the trial sites were “acceptable to support” the application.

In the more recent phase 3 study, the safety profile for Imdelltra was “consistent” with its known profile. The drug comes with a black-box warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. In the phase 2 trial, 55% of patients who used the therapy experienced CRS.

Imdelltra picked up $115 million in 2024 sales and has been pegged as a potential blockbuster with William Blair analysts previously projecting $842 million in 2028 sales. The company is also weighing the drug in several studies across earlier lines of SCLC treatment both on its own and in combination regimens.

https://www.fiercepharma.com/pharma/amgen-pads-imdelltras-case-tough-treat-lung-cancer-subtype-phase-3-survival-win