AACR 2026: Pembrolizumab Bowel Cancer Success, Moderna Melanoma Data

Key Takeaways

• NEOPRISM-CRC (NCT05197322) reported zero relapses after three years in pembrolizumab-treated mismatch repair deficient (MMR-d) colorectal cancer, with a 59% pathological complete response rate.
• Moderna's mRNA-4359 plus pembrolizumab (NCT05533697) achieved 83% objective response rate (ORR) and 92% disease control rate (DCR) in first-line melanoma.
• Daraxonrasib (RMC-6236; NCT05379985) showed 35% ORR in second-line RAS-mutated pancreatic cancer with median overall survival (OS) of 13.1 months.
• ICI-related myocarditis within the first 30 days carries elevated fatality risk, per University of Oklahoma research presented at AACR.

What Is the AACR Annual Meeting?

The American Association for Cancer Research (AACR) Annual Meeting 2026 took place April 17-22 in San Diego, California. The meeting brought together researchers, clinicians, and biotech executives to share pivotal data across oncology.

This article summarizes key findings including neoadjuvant immunotherapy results, individual neoantigen therapy combinations, RAS pathway inhibitors, and immune-related adverse events data.

What Did the NEOPRISM-CRC Trial Achieve?

The NEOPRISM-CRC study (NCT05197322) is a Phase II trial led by University College London (UCL) and University College London Hospitals. It evaluates neoadjuvant pembrolizumab (Keytruda) in patients with high-risk stage II/III mismatch repair deficient (MMR-d) colorectal cancer.

After approximately three years of follow-up, the trial reported zero relapses in patients who received nine weeks of pembrolizumab prior to surgery. The study achieved a 59% pathological complete response (pCR) rate. Personalized circulating tumor DNA (ctDNA) monitoring showed predictive value for treatment response.

The trial is actively recruiting with an estimated primary completion date of July 2026. Collaborators include Merck Sharp & Dohme (Keytruda sponsor), Foundation Medicine, and Personalis.

How Did Moderna's mRNA-4359 Perform?

Moderna presented Phase 1/2 results for mRNA-4359 in combination with pembrolizumab as first-line treatment for advanced melanoma (NCT05533697, Arm 2a).

The combination achieved an 83% objective response rate (ORR) and a 92% disease control rate (DCR) per RECIST v1.1 criteria. Two complete responses were observed in the cohort of treatment-naïve patients.

mRNA-4359 is an individualized neoantigen therapy (INT). It uses mRNA encoding patient-specific tumor antigens to stimulate T-cell responses when combined with PD-1 blockade. The FDA granted Fast Track designation to mRNA-4359.

What Is Daraxonrasib's Efficacy in Pancreatic Cancer?

Revolution Medicines announced data for daraxonrasib (RMC-6236), an oral RAS(ON) multiselective inhibitor. The compound targets guanosine triphosphate-bound mutant and wild-type RAS proteins.

In the Phase 1-2 RMC-6236-001 study (NCT05379985), 26 patients with RAS G12 mutations received daraxonrasib at 300 mg in the second-line setting. The objective response rate was 35% (95% CI: 17-56). Median progression-free survival (PFS) was 8.5 months and median overall survival (OS) was 13.1 months.

Results were published in the New England Journal of Medicine. Treatment-related grade 3+ adverse events occurred in 30% of patients. Rash, diarrhea, nausea, and fatigue were the most common toxicities.

What Predicts Fatality in ICI-Related Myocarditis?

University of Oklahoma Stephenson Cancer Center researchers presented data from WHO VigiBase pharmacovigilance analysis at AACR 2026. Early-onset immune checkpoint inhibitor (ICI)-related myocarditis predicts increased mortality risk.

Myocarditis occurring within the first 30 days of ICI therapy is a critical risk window. Reported fatality rates for ICI-related myocarditis range from 20-50% across studies.

The analysis also examined triple M overlap syndrome (TMOS). This rare phenotype combines myocarditis with myositis and myasthenia gravis. TMOS associates with earlier onset and higher severity than myocarditis alone.

What Other Data Emerged at AACR 2026?

• Oral precancer immunotherapy: A Phase I trial showed direct injection immunotherapy can shrink oral precancerous lesions, potentially avoiding surgery.
• AI applications: Plenary sessions highlighted artificial intelligence tools transforming cancer pathology and clinical practice.
• Zoldonrasib update: Revolution Medicines reported Phase 1 data in KRAS G12D lung cancer showing 52% confirmed ORR and 93% disease control rate.
• Preclinical programs: Data on Cbl-b inhibitors, CDK4 inhibitors, and novel immuno-oncology constructs were presented.

How Do These Findings Affect the Market?

The AACR 2026 data reveal three concurrent trends. First, neoadjuvant immuno-oncology approaches are expanding from melanoma into colorectal and other solid tumors (learn more). Second, individual neoantigen therapies are advancing from concept into combination strategies. Third, RAS pathway inhibition continues to yield outcomes in historically difficult-to-treat cancers.

For market participants, these data inform pipeline valuation and competitive positioning across immuno-oncology and targeted therapy sectors.

What Should Investors Watch Next?

Several readouts merit monitoring. NEOPRISM-CRC's primary completion is anticipated in July 2026. Moderna's mRNA-4359 program should advance into pivotal trials following the Phase 1/2 melanoma data. Revolution Medicines has initiated Phase 3 trials evaluating daraxonrasib in first-line pancreatic cancer.

ASCO 2026 will likely provide further updates on these programs.

Frequently Asked Questions

Primary Sources

1. ClinicalTrials.gov. NEOPRISM-CRC: Neoadjuvant Pembrolizumab for MMR-deficient Colorectal Cancer. Trial identifier: NCT05197322. U.S. National Library of Medicine.
2. ClinicalTrials.gov. Study of mRNA-4359 Alone and in Combination with Immune Checkpoint Blockade. Trial identifier: NCT05533697. U.S. National Library of Medicine.
3. Revolution Medicines. Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer. N Engl J Med. DOI: 10.1056/NEJMoa2505783.
4. ClinicalTrials.gov. RMC-6236 in Patients with Advanced Solid Tumors. Trial identifier: NCT05379985. U.S. National Library of Medicine.
5. Abushukair HM, Naqash AR, Oh TG, et al. Early Immune Checkpoint Inhibitor-Related Myocarditis Signals Elevated Mortality Risk. Presented at AACR Annual Meeting 2026. Data published in The ASCO Post. May 25, 2026. URL: ascopost.com.
6. Moderna Inc. IR Insights: Recapping Moderna's mRNA-4359 Presentation at 2026 AACR Annual Meeting. April 20, 2026. URL: modernatx.com.

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