Another bump in Moderna’s neoantigen road
In 2022 Merck & Co exercised its option to develop and commercialise Moderna's personalised immunotherapy intismeran autogene (mRNA-4157), adding another $250m to the companies' 2016 deal. Since then, progress has been bumpy, and the latest setback has surfaced in perioperative cutaneous squamous cell carcinoma where the Interpath-007 pivotal trial appears to have been quietly terminated. According to clinicaltrials.gov, enrolment into the phase 2 portion was stopped after only 46 patients, and the planned phase 3 will not proceed, a move that came after Keytruda’s failure in the same indication, in Keynote-630. Earlier, phase 2 data with intismeran autogene in adjuvant melanoma were positive, but the FDA deemed them insufficient for accelerated approval, despite the phase 3 Interpath-001 study being substantially enrolled. Beyond melanoma, two adjuvant non-small cell lung cancer studies are ongoing, both unlikely to readout before 2030. Two additional phase 2 studies are under way in other adjuvant settings, and the companies are now eyeing new fronts such as first-line melanoma; however, BioNTech and Roche’s rival project, autogene cevumeran, failed in this setting in March, with BioNTech speculating that the neoantigen approach could work better in adjuvant disease, where tumour burden is lower.
Interpath trials
| Study | Trial phase | Setting | Design/primary endpoints | Note |
|---|---|---|---|---|
| Interpath-001 | Phase 3 | Adjuvant stage IIb or IIc, III or IV cutaneous melanoma | Keytruda combo vs Keytruda; recurrence-free survival | Readout expected Sep 2026; FDA not supportive of accelerated approval |
| Interpath-002 | Phase 3 | Adjuvant stage II, IIIa, IIIb (N2) NSCLC | Keytruda combo vs Keytruda; disease-free survival | Readout expected Jun 2030 |
| Interpath-009 | Phase 3 | Adjuvant stage II, IIIa, IIIb (N2) NSCLC, post neoadjuvant treatment | Keytruda combo vs Keytruda; disease-free survival | Readout expected May 2033 |
| Interpath-004 | Phase 2 | Adjuvant intermediate & high risk renal cancer | Keytruda combo vs Keytruda; disease-free survival | Readout expected Jan 2028 |
| Interpath-005 | Phase 2 | Neoadjuvant & adjuvant high-risk muscle-invasive urothelial carcinoma | Keytruda combo vs Keytruda/ perioperative cohort: Padcev + Keytruda combo; disease-free survival | Readout expected April 2027 |
| Interpath-011 | Phase 2 | High-risk non-muscle invasive bladder cancer (BCG-naive) | BCG combo vs BCG; event-free survival | Readout expected Sep 2031 |
| Interpath-012 | Phase 2 | First-line melanoma | Keytruda combo vs Keytruda; progression-free survival | Readout expected Jul 2028 |
| Interpath-007 | Phase 3 | (Neo)adjuvant locally advanced stage II-IV (M0) cutaneous squamous cell carcinoma | Keytruda combo as neoadjuvant therapy, followed by Keytruda combo as adjuvant therapy, vs Keytruda + SoC (phase 2 stage only), or SoC alone; event-free survival | Enrolment stopped; no phase 3 expansion |
Source: OncologyPipeline.
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