Moderna and Merck’s personalized mRNA cancer therapy hits both key Phase 3 endpoints in melanoma
Moderna and Merck have announced positive Phase 3 results for intismeran autogene, their individualized mRNA-based cancer therapy, combined with Keytruda in patients with high-risk melanoma that had been completely removed by surgery.
The INTerpath-001 trial met:
- Its primary endpoint of recurrence-free survival (RFS)
- A key secondary endpoint of distant metastasis-free survival (DMFS)
The combination produced statistically significant and clinically meaningful improvements on both measures compared with Keytruda alone.
This is significant because Merck and Moderna say it represents the first positive Phase 3 trial for an individualized neoantigen therapy and an mRNA-based cancer therapy.
Intismeran isn't an off-the-shelf treatment.
A patient's tumor is analyzed for its unique mutations, and an individualized mRNA therapy is created containing instructions for up to 34 tumor-specific neoantigens. The goal is to train the immune system to recognize and attack cancer cells carrying those mutations.
The Phase 3 trial enrolled 1,137 patients with completely resected stage IIB-IV melanoma.
Patients were randomized 2:1 to receive either:
Intismeran + Keytruda
or
Keytruda alone.
One important caveat: Merck and Moderna haven't released the actual Phase 3 hazard ratios or detailed numbers yet.
The companies plan to present the full data at an upcoming medical meeting and discuss regulatory submissions with health authorities. The trial is also continuing to evaluate overall survival.
Safety was consistent with previous studies, with no new safety signals reported.
There was already encouraging evidence from the earlier Phase 2b study.
At five-year follow-up, intismeran + Keytruda reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death by 59% compared with Keytruda alone. Those figures are from the earlier study, not the new Phase 3 readout.
Merck and Moderna are now studying the technology across nine Phase 2 and Phase 3 trials, including melanoma, lung, bladder, and kidney cancers.
This feels like an important milestone for mRNA technology.
COVID vaccines showed that mRNA could be manufactured and deployed at massive scale.
Cancer presents a very different challenge: instead of giving everyone essentially the same vaccine, this approach attempts to create a different treatment for each patient's tumor.
If the full Phase 3 results hold up and regulators approve it, personalized mRNA cancer therapy could move from an experimental idea toward an actual part of mainstream oncology.
Sources:
Merck — Phase 3 INTerpath-001 results