Intismeran Autogene (V940): First mRNA Cancer Vaccine to Meet a Phase 3 Endpoint — INTerpath-001 Melanoma Positive (August 2026), Personalized Neoantigen Vaccine, Moderna + Merck

Last updated: August 20, 2026

🚨 Landmark result (August 19, 2026): Merck and Moderna announced that the Phase 3 INTerpath-001 trial of intismeran autogene (V940 / mRNA-4157) + KEYTRUDA (pembrolizumab) met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS) in patients with completely resected high-risk (Stage IIB–IV) melanoma — described as "statistically significant and clinically meaningful" improvements versus KEYTRUDA alone (1,137 patients, randomized 2:1). This is the first individualized neoantigen therapy — and the first mRNA cancer vaccine — to succeed in a Phase 3 trial. Full data (including hazard ratios) will be presented at an upcoming medical meeting, and the companies plan to discuss regulatory filings. Intismeran remains investigational (no FDA approval yet). The trials listed below are the actively-recruiting INTerpath studies (NSCLC and others); INTerpath-001 itself is no longer recruiting.

About Intismeran Autogene (V940)

Drug profile:

Intismeran autogene (development codes V940 and mRNA-4157) is an investigational personalized neoantigen mRNA cancer vaccine co-developed by Moderna (mRNA platform) and Merck (combination partner via pembrolizumab / KEYTRUDA). There is no brand name yet, and intismeran autogene remains investigational with no FDA approvals as of August 2026 — but on August 19, 2026 it became the first mRNA cancer vaccine to succeed in a Phase 3 trial (INTerpath-001, adjuvant resected melanoma; see the alert above).

Mechanism of action:

V940 is not a one-size-fits-all vaccine. Each patient receives a custom-manufactured mRNA encoding approximately 34 neoantigens specific to their own resected tumor. The workflow: (1) the patient's tumor is sequenced after surgical resection, (2) computational pipelines predict which mutated peptides (neoantigens) are most likely to be presented by that patient's HLA molecules to T cells, (3) a bespoke mRNA encoding approximately 34 of those neoantigens is manufactured for that specific patient, (4) the mRNA is delivered via lipid-nanoparticle injection. In clinical trials V940 is almost always combined with pembrolizumab: the vaccine is designed to prime tumor-specific T cells, and pembrolizumab releases the PD-1 brake so those T cells can attack residual microscopic disease. This is fundamentally different from earlier cancer vaccines that targeted "shared" tumor antigens (NY-ESO-1, MAGE) common across many patients.

Regulatory status:

FDA approvals: none. Intismeran autogene is investigational.
FDA designations: Breakthrough Therapy Designation in adjuvant resected high-risk Stage III-IV melanoma, granted on the strength of the 2023 Phase 2b KEYNOTE-942 / mRNA-4157-P201 readout (adjuvant V940 + pembrolizumab vs pembrolizumab alone — substantial recurrence-free survival benefit).
Phase 3 — melanoma (INTerpath-001, POSITIVE): the confirmatory Phase 3 in adjuvant resected melanoma, INTerpath-001, read out positive on August 19, 2026 — meeting its primary endpoint (recurrence-free survival) and a key secondary endpoint (distant metastasis-free survival) in completely resected Stage IIB–IV melanoma, the first Phase 3 win for any mRNA cancer vaccine. That trial is not in the ClinTrialFinder corpus because it is no longer recruiting.
Phase 3 — NSCLC (recruiting): three Phase 3 trials are recruiting, all in NSCLC: INTerpath-002 (NCT06077760, adjuvant Stage II-IIIB resected), INTerpath-009 (NCT06623422, adjuvant resectable Stage II-IIIB patients who did not achieve pCR after neoadjuvant pembrolizumab + chemo), and INTerpath-014 (NCT07513376, adjuvant high-risk Stage I resected with subcutaneous pembrolizumab coformulation).
Anticipated first approval: the resected melanoma adjuvant indication is the lead candidate, now supported by the positive INTerpath-001 Phase 3 readout (Aug 19, 2026). Merck and Moderna have said they plan to discuss regulatory filings; a submission is the expected next step. No approval has been granted yet.

Active Research Directions in 2026

Adjuvant resected NSCLC (the new Phase 3 frontier) — three Phase 3 trials now cover three slices of the resected NSCLC population: INTerpath-002 (Stage II-IIIB, adjuvant after complete resection), INTerpath-009 (Stage II-IIIB resectable patients who did NOT achieve pCR after neoadjuvant pembrolizumab + platinum doublet — a particularly high-risk residual-disease population), and INTerpath-014 (high-risk Stage I, with a subcutaneous pembrolizumab coformulation arm). These three together aim to test the personalized-vaccine adjuvant hypothesis across the spectrum of resected NSCLC.
First-line advanced melanoma (Phase 2) — INTerpath-012 (NCT06961006) extends V940 from the adjuvant setting (KEYNOTE-942) into advanced / unresectable / metastatic 1L melanoma in combination with pembrolizumab. Important nuance: unlike the adjuvant setting (where the vaccine is made from the resected tumor), the advanced-disease setting must use sequencing from a biopsy of the metastatic lesion.
First-line metastatic squamous NSCLC (Phase 2) — INTerpath-013 (NCT07221474) adds V940 on top of standard 1L pembrolizumab + chemotherapy in metastatic squamous NSCLC, a population that does not currently have ADC or targeted-therapy alternatives.
High-risk non-muscle invasive bladder cancer (NMIBC) + BCG (Phase 2) — INTerpath-011 (NCT06833073) tests V940 + BCG vs BCG alone in high-risk NMIBC. This is the only V940 trial without pembrolizumab as the combination partner — instead pairing the personalized vaccine with intravesical BCG (the standard immunologic therapy in NMIBC).
Other resected solid tumors (future) — Moderna and Merck have publicly described plans for INTerpath programs across additional resected tumor types (renal cell carcinoma, hepatocellular carcinoma, others). Those programs are not in the recruiting corpus as of August 2026; we will add them when they open.

Trials by Setting

Phase 3 Adjuvant Resected NSCLC (3 recruiting)

NCT06077760 — INTerpath-002 / V940-002 (Phase 3; Recruiting): Adjuvant V940 (intismeran autogene) + pembrolizumab vs placebo + pembrolizumab in participants with completely resected Stage II, IIIA, or IIIB (N2) non-small cell lung cancer. Randomized, double-blind, placebo- and active-comparator-controlled. This is the lead Phase 3 in NSCLC and the trial referenced in the ASCO 2026 wrap-up (Takeaway #7). Lead sponsors: Moderna + Merck.
NCT06623422 — INTerpath-009 / V940-009 (Phase 3; Recruiting): Adjuvant pembrolizumab with or without V940 in participants with resectable Stage II to IIIB (N2) NSCLC who did NOT achieve a pathologic complete response (pCR) after receiving neoadjuvant pembrolizumab + platinum-based doublet chemotherapy. Randomized, double-blind. Targets the highest-risk subset of perioperative-pembrolizumab patients — those with residual disease at surgery. Lead sponsors: Moderna + Merck.
NCT07513376 — INTerpath-014 / V940-014 (Phase 3; Recruiting): Adjuvant intismeran autogene with or without subcutaneous pembrolizumab coformulated with berahyaluronidase alfa (MK-3475A) vs placebo in participants with completely resected high-risk Stage I NSCLC. Also includes an intismeran monotherapy arm. Lead sponsors: Moderna + Merck.

Phase 2 Advanced Melanoma (1 recruiting)

NCT06961006 — INTerpath-012 / V940-012 (Phase 2; Recruiting): V940 (mRNA-4157) + pembrolizumab vs placebo + pembrolizumab as first-line treatment for advanced (unresectable / metastatic) melanoma. Randomized, double-blind, placebo- and active-comparator-controlled. Extends the personalized-vaccine + PD-1 hypothesis from the adjuvant resected setting (KEYNOTE-942) into the advanced-disease 1L setting. Lead sponsors: Moderna + Merck.

Phase 2 Metastatic Squamous NSCLC (1 recruiting)

NCT07221474 — INTerpath-013 / V940-013 (Phase 2; Recruiting): V940 + pembrolizumab + chemotherapy vs placebo + pembrolizumab + chemotherapy as first-line treatment for metastatic squamous NSCLC. Randomized, double-blind. Tests whether adding the personalized vaccine on top of the current 1L standard improves outcomes in a population with limited ADC / targeted alternatives. Lead sponsors: Moderna + Merck.

Phase 2 High-Risk Non-Muscle Invasive Bladder Cancer (1 recruiting)

NCT06833073 — INTerpath-011 / V940-011 (Phase 2; Recruiting): V940 in combination with BCG vs BCG monotherapy in participants with high-risk non-muscle invasive bladder cancer (including carcinoma in situ). Open-label, randomized. The only V940 trial in our corpus without pembrolizumab as the combination partner — here the immunologic combination is V940 + intravesical BCG. Lead sponsors: Moderna + Merck.

Showing the V940 / intismeran autogene trials in the ClinTrialFinder corpus as of August 2026. The Phase 2b KEYNOTE-942 (mRNA-4157-P201) adjuvant melanoma trial — the source of the 2023 RFS signal and FDA Breakthrough Therapy Designation — and the confirmatory Phase 3 INTerpath-001 adjuvant resected melanoma trial are not in the corpus because they are not currently recruiting. View the latest intismeran search on ClinicalTrials.gov.

Trials Not Yet Recruiting

No V940 trials are listed as "Not yet recruiting" in our corpus as of June 13, 2026. All six trials above are actively recruiting. New INTerpath programs (planned for additional resected solid tumors per sponsor announcements) will be added when they open enrollment.

Patient Selection and Practical Considerations

Eligibility for V940 trials is driven by surgical and disease-stage criteria rather than a specific biomarker like KRAS or HER2:

Resected tumor tissue available — for the adjuvant NSCLC trials (INTerpath-002, -009, -014), the vaccine is manufactured from the patient's own resected tumor. Sufficient tumor tissue from the surgical specimen is required for sequencing and neoantigen prediction. This is a logistical constraint, not a biomarker test.
Stage and disease setting matter — INTerpath-002 enrolls Stage II, IIIA, IIIB (N2) NSCLC after complete resection; INTerpath-009 specifically enrolls Stage II-IIIB resectable patients who did NOT achieve pCR after neoadjuvant pembrolizumab + platinum doublet; INTerpath-014 enrolls high-risk Stage I after complete resection. The advanced melanoma trial (INTerpath-012) enrolls 1L unresectable/metastatic melanoma; the metastatic squamous NSCLC trial (INTerpath-013) enrolls 1L metastatic squamous NSCLC.
Manufacturing timeline — because the vaccine is custom-made for each patient, there is a manufacturing window (typically several weeks) between surgery / biopsy and the start of vaccine dosing. Trial protocols define how adjuvant chemotherapy and pembrolizumab are sequenced during that window; pembrolizumab is generally started first while the vaccine is being made.
HLA typing — the neoantigen prediction pipeline uses each patient's HLA type to choose which mutated peptides are most likely to be presented to T cells. HLA typing is part of the screening process.
Site participation is the bigger gate than eligibility — because personalized mRNA manufacturing requires tumor shipping, sequencing, and a centralized manufacturing facility, only a subset of cancer centers participate. Geographic access is often the binding constraint. Ask your oncologist whether your treating center is an INTerpath site or whether you would need to travel.

Side Effects and Practical Considerations

Safety data to date are largely from the Phase 2b KEYNOTE-942 melanoma trial (V940 + pembrolizumab vs pembrolizumab alone, adjuvant resected high-risk Stage III-IV melanoma). The Phase 3 INTerpath program is still accumulating safety data.

Local injection-site reactions — the most common V940-attributed adverse event. Generally Grade 1-2, self-limited, similar to other intramuscular mRNA vaccines.
Flu-like reactogenicity — chills, fever, headache, myalgias, fatigue — the typical mRNA-vaccine pattern, usually within 24-48 hours of dosing. Generally Grade 1-2, manageable with supportive care.
Fatigue — common with V940 alone and amplified by the pembrolizumab combination.
Pembrolizumab-class immune-related adverse events (when combined with pembrolizumab) — thyroid dysfunction, pneumonitis, colitis, hepatitis, skin rash, rare endocrinopathies (hypophysitis, type 1 diabetes), and rare cardiac, renal, or neurologic immune events. Managed with the standard PD-1 inhibitor irAE algorithm.
BCG-class events (in the INTerpath-011 bladder trial) — urinary frequency, dysuria, cystitis, hematuria from intravesical BCG instillation; rare systemic BCG reactions.
Long-term safety — still being characterized. The Phase 3 INTerpath program will provide the definitive safety profile.

Frequently Asked Questions

What is intismeran autogene (V940 / mRNA-4157)?

Intismeran autogene (development codes V940 and mRNA-4157) is an investigational personalized neoantigen mRNA cancer vaccine co-developed by Moderna and Merck. It is NOT a one-size-fits-all vaccine: each patient receives a custom-manufactured mRNA encoding approximately 34 neoantigens specific to their own resected tumor. Tumor tissue is sequenced after surgery, neoantigens most likely to be presented by that patient's HLA molecules are predicted computationally, and a personalized mRNA is then manufactured. The vaccine is almost always combined with pembrolizumab (KEYTRUDA). The lead clinical signal came from the Phase 2b KEYNOTE-942 / mRNA-4157-P201 trial in adjuvant resected high-risk Stage III-IV melanoma (substantial RFS benefit reported in 2023, FDA Breakthrough Therapy Designation). Intismeran autogene remains investigational and has no FDA approvals as of August 2026, but on August 19, 2026 the confirmatory Phase 3 INTerpath-001 trial (adjuvant resected Stage IIB-IV melanoma) read out positive on both recurrence-free survival and distant metastasis-free survival — the first Phase 3 success for any mRNA cancer vaccine.

What cancers and trial settings is V940 being tested in?

Six V940 trials are recruiting in our corpus. Three Phase 3 in NSCLC: INTerpath-002 (NCT06077760, adjuvant V940 + pembrolizumab in resected Stage II-IIIB NSCLC); INTerpath-009 (NCT06623422, adjuvant pembrolizumab ± V940 in Stage II-IIIB patients who did NOT achieve pCR after neoadjuvant pembro + chemo); INTerpath-014 (NCT07513376, adjuvant V940 ± subcutaneous pembrolizumab coformulation in resected high-risk Stage I NSCLC). Three Phase 2: INTerpath-012 (NCT06961006, V940 + pembrolizumab in 1L advanced melanoma); INTerpath-013 (NCT07221474, V940 + pembrolizumab + chemo in 1L metastatic squamous NSCLC); INTerpath-011 (NCT06833073, V940 + BCG in high-risk non-muscle invasive bladder cancer). KEYNOTE-942 and INTerpath-001 adjuvant resected melanoma trials are not in the current corpus because they are not actively recruiting.

How is V940 different from a flu vaccine or other cancer vaccines?

A flu vaccine is one-size-fits-all: every recipient gets the same antigens. V940 is the opposite — it is fully personalized. After surgical resection, the patient's own tumor is sequenced, and computational pipelines predict which neoantigens (mutated peptides unique to that tumor) are most likely to be presented by the patient's HLA molecules to T cells. A bespoke mRNA encoding approximately 34 of those neoantigens is then manufactured for that specific patient — no two patients receive the same vaccine. This is also different from earlier cancer vaccines targeting "shared" tumor antigens (NY-ESO-1, MAGE) common across many patients. V940 is co-developed by Moderna (mRNA platform) and Merck (which contributes pembrolizumab). The biological hypothesis: V940 primes tumor-specific T cells, and pembrolizumab releases the PD-1 brake so those T cells can attack residual microscopic disease after surgery.

What are the main side effects of V940?

From the Phase 2b KEYNOTE-942 melanoma trial (the most extensively reported safety dataset to date), the most common V940-attributed events have been local injection-site reactions, fatigue, and flu-like symptoms (chills, fever, headache, myalgias) — the typical mRNA-vaccine pattern. Most events were Grade 1-2 and self-limited. When combined with pembrolizumab, patients also face the standard PD-1 inhibitor immune-related adverse event profile: thyroid dysfunction, pneumonitis, colitis, hepatitis, skin reactions, rare endocrinopathies. The Phase 3 INTerpath program is still accumulating safety data. Patients should expect close monitoring for both vaccine-reactogenicity events and pembrolizumab-class immune-related events.

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