hypb-interpath-001-phase3

GROUNDING — INTerpath-001 Phase 3 topline, and KEYNOTE-942 5-year follow-up

Source A — Merck press release, Phase 3 INTerpath-001

• URL: https://www.merck.com/news/merck-and-moderna-announce-phase-3-interpath-001-trial-of-intismeran-autogene-plus-keytruda-met-endpoints-of-recurrence-free-survival-rfs-and-distant-metastasis-free-survival-dmfs-in-patient/
• Accessed: 2026-08-21
• Exact query: WebSearch intismeran autogene mRNA-4157 INTerpath-001 NCT05933577 Phase 3 recurrence-free survival interim analysis 1137 patients, then WebFetch of the Merck URL with a prompt asking for verbatim drug identity, trial name, NCT, enrollment, endpoints, interim-analysis status, “first” claims, mechanism/manufacturing description, route and dose, and hazard ratios.

Verbatim passages

“Intismeran autogene (intismeran; V940 or mRNA-4157), a novel investigational mRNA-based individualized neoantigen therapy (INT)”

Trial name: “INTerpath-001”; NCT Number: “NCT05933577”; Enrollment: “1,137 patients”; Analysis type: “Pre-specified interim analysis”

Primary endpoint: “Recurrence-free survival (RFS)“. Secondary endpoint: “Distant metastasis-free survival (DMFS)“.

“First positive Phase 3 readout for an individualized neoantigen therapy (INT) and for an mRNA-based cancer therapy”

“Each therapy consists of a synthetic mRNA coding for up to 34 neoantigens and is tailored to the unique biology of an individual patient’s tumor.”

“Designed and produced using a patient’s tumor sample to identify the unique mutational signature, or ‘fingerprint,’ of their cancer”

“Intismeran (1 mg every three weeks for up to nine doses)” combined with “KEYTRUDA (400 mg every six weeks up to nine cycles)”

Prior Phase 2b: RFS “49% reduction…HR=0.51; [95% CI, 0.294-0.887]”; DMFS “59% reduction…HR=0.411; [95% CI, 0.200-0.843]“

Source B — Merck press release, KEYNOTE-942 5-year data

• URL: https://www.merck.com/news/moderna-merck-announce-5-year-data-for-intismeran-autogene-in-combination-with-keytruda-pembrolizumab-demonstrated-sustained-improvement-in-the-primary-endpoint-of-recurrence-free-survival-i/
• Accessed: 2026-08-21
• Exact query: WebSearch mRNA-4157 V940 KEYNOTE-942 five-year hazard ratio 0.51 recurrence-free survival distant metastasis 0.411, then WebFetch of the Merck 5-year URL with a prompt asking verbatim for HRs, CIs, risk reductions, n, individualization/manufacturing description, and route.

Verbatim passages

5-year RFS: Hazard ratio “0.510”, 95% CI “[0.294–0.887]”, risk reduction “49%” compared to KEYTRUDA alone.

“157 patients with high-risk stage III/IV melanoma” enrolled in the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial

“a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumor”

Administration: intismeran autogene “1 mg every three weeks for nine doses” combined with KEYTRUDA 200 mg every three weeks for up to 18 cycles.

Evidential weight

• STATES (all facts in the brief verified): intismeran autogene = V940 = mRNA-4157; individualized neoantigen therapy; completely resected Stage IIB-IV cutaneous melanoma with pembrolizumab (indication from the Moderna IR page, see hypb-moderna-ir-insights.md); INTerpath-001; NCT05933577; n = 1,137; met primary RFS and secondary DMFS at a pre-specified interim analysis; RFS HR 0.51 (95% CI 0.294–0.887, 49% reduction); DMFS HR 0.411 (95% CI 0.200–0.843, 59% reduction); first positive Phase 3 readout for an individualized neoantigen therapy and for an mRNA-based cancer therapy.
• Important qualifier for correct use: the HR figures 0.51 / 0.411 are from the Phase 2b KEYNOTE-942 trial (n = 157), restated in the Phase 3 press release as prior data. They are NOT the Phase 3 effect size. The Phase 3 topline is qualitative (“met endpoints”); no Phase 3 HR is published in these sources. Any use of 0.51/0.411 must be attributed to the Phase 2b, 5-year follow-up.
• STATES on the “bespoke” mechanism, which is the load-bearing fact for channel (i): the individualization is a sequence choice — “up to 34 neoantigens” selected from the patient’s tumour mutational signature — encoded into synthetic mRNA. Chemistry, dose (1 mg), schedule (q3w x 9) and route are fixed and identical across patients. The press release does not describe any per-patient change to formulation, LNP composition, or process.
• NOT STATED in these sources: manufacturing turnaround time; regulatory designations; route of administration named explicitly as intramuscular (dose is stated, route is not) — do not claim IM from these sources.