KRAS pancreatic cancer vaccine triggers immune response in 99% of patients, phase 3 trial planned

Overview

Updated Yesterday

About 90% of pancreatic cancers are driven by mutations in the KRAS gene, which has long been considered undruggable. An experimental vaccine called camupepimut (ELI-002 7P) is designed to teach the immune system to recognize seven common KRAS mutations, and the phase 2 AMPLIFY-7P trial results show it worked: 89 of 90 evaluable patients (98.9%) developed KRAS-specific T-cell responses.

The trial did not meet its primary endpoint — median disease-free survival was 23.8 months with the vaccine versus 21.2 months with observation, a difference that wasn't statistically significant. But the immune signal was striking: patients whose T-cell response rose more than ninefold over baseline had dramatically longer disease-free survival (median not reached versus 6.08 months for weaker responders). The manufacturer now plans a confirmatory phase 3 trial.

Why it matters

Pancreatic cancer has a 13% five-year survival rate; if this vaccine delays recurrence after surgery, it could become the first immunotherapy that works in the disease.

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Key Indicators

98.9%

Patients developing KRAS-specific T-cell responses

89 of 90 evaluable patients who received camupepimut mounted an immune response.

9.17-fold

T-cell response threshold associated with prolonged DFS

Responses above 9.17x baseline correlated with longer disease-free survival (HR 0.22).

23.8 vs 21.2 months

Median disease-free survival: vaccine vs observation

Primary endpoint not met (HR 0.85, P = 0.5329); post hoc adjusted HR was 0.47.

95.5%

Patients with persistent T-cell response at 46 weeks

Immune responses persisted in evaluable patients at least 46 weeks after study start.

86.7%

Patients showing antigen spreading

Immune responses expanded beyond the vaccine's targets to other tumor antigens (13 of 15 evaluable).

Voices

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People Involved

Peter Hosein

Gastrointestinal oncologist, Sylvester Comprehensive Cancer Center

Principal investigator of new V Foundation-funded research combining camupepimut with RAS inhibitors

Organizations Involved

Elicio Therapeutics

Biotechnology company

Developer of camupepimut (ELI-002 7P)

Developer of the lymph node-targeted amphiphile vaccine platform used in the AMPLIFY-7P trial.

Mayo Clinic

Academic medical center

Lead trial site for AMPLIFY-7P

Academic medical center that led the randomized phase 2 AMPLIFY-7P trial and published the results in Nature Medicine.

Timeline

October 2023 October 2026

3 events Latest: Yesterday

October 2026
AMPLIFY-7P results published in Nature Medicine
Latest Publication

Phase 2 results show camupepimut generated T-cell responses in 98.9% of patients; primary DFS endpoint not met; phase 3 planned.
Yesterday
January 2024
AMPLIFY-7P trial launches
Trial start

Phase 2 trial enrolled 144 patients with stage I-III KRAS-mutated pancreatic cancer who had no recurrence within six months of standard therapy.
January 2024
October 2023
AMPLIFY-201 phase 1 results published
Publication

Phase 1 AMPLIFY-201 trial showed ELI-002 2P generated mKRAS-specific T-cell responses in most patients with KRAS-mutated pancreatic and colorectal cancer.
October 13th, 2023

Scenarios

Phase 3 trial confirms DFS benefit with extended dosing

Possible Resolves by End of 2029

Discussed by: Trial authors in Nature Medicine publication

The phase 3 design will extend camupepimut treatment beyond the six-month period used in phase 2, since the DFS advantage coincided with dosing duration. It will also exclude patients with prior radiation (associated with lymphopenia and poor immunogenicity) and stratify by circulating tumor DNA status. If the adjusted HR of 0.47 holds, the trial could show significant recurrence delay.

Combination with RAS inhibitors and checkpoint blockade succeeds

Possible Resolves by End of 2028

Discussed by: Peter Hosein, Sylvester Comprehensive Cancer Center; Elicio Therapeutics

A planned multicenter phase 1 trial will test camupepimut with daraxonrasib (a RAS(ON) inhibitor) with or without nivolumab in metastatic KRAS-mutated pancreatic cancer. The hypothesis: blocking RAS-driven immune suppression could strengthen vaccine-primed T-cell activity. An ongoing trial (NCT07671339) is already evaluating combination with checkpoint inhibitors in the neoadjuvant setting.

Overall survival data disappoint despite T-cell response

Unlikely Resolves by End of 2029

Discussed by: Mayo Clinic researchers (noted results pending)

The Nature Medicine publication notes overall survival data are not yet available, and some findings linking immune response to DFS came from exploratory analyses. It remains possible that the DFS signal does not translate to an OS benefit, particularly given the post hoc nature of many subgroup findings. The association between T-cell magnitude and DFS is correlational, not causal.

Historical Context

2 moments from history that rhyme with this story — and how they unfolded.

1980s-2013

KRAS declared 'undruggable' (1980s-2010s)

KRAS mutations were identified in the early 1980s as among the most common oncogenes in human cancer. For three decades, attempts to develop drugs targeting the mutated protein failed; the protein lacks the deep binding pockets that typical small-molecule drugs need, leading researchers to call it undruggable.

Then

A generation of drug development efforts focused on downstream pathways instead of KRAS itself.

Now

The 2013 breakthrough by Kevan Shokat's lab at UCSF found a covalent-binding pocket on the G12C variant, leading to sotorasib and adagrasib approvals in lung cancer in 2021-2022. However, pancreatic cancer's most common KRAS variants (G12D, G12V) remained harder to drug.

Why this matters now

Vaccines take a different approach than small molecules: instead of blocking the mutated protein, they train T cells to recognize and kill cancer cells presenting KRAS peptides. This sidesteps the 'undruggable' problem entirely.

April 2010

Provenge, first therapeutic cancer vaccine (2010)

The FDA approved sipuleucel-T (Provenge), a personalized vaccine for metastatic prostate cancer, after a phase 3 trial showed a 4.1-month median overall survival benefit. It was the first therapeutic cancer vaccine ever approved.

Then

Provenge was a commercial failure — production costs made it unprofitable, and Dendreon filed for bankruptcy in 2014.

Now

The experience taught researchers that autologous (patient-derived) vaccines were too expensive and slow. Modern neoantigen vaccines use off-the-shelf or rapid-manufacturing platforms, which is why KRAS vaccines like camupepimut can reach hundreds of patients in trials.

Why this matters now

Camupepimut is an off-the-shelf vaccine targeting the seven most common KRAS mutations, covering about 90% of pancreatic cancers. It avoids the cost and logistics problems that sank Provenge.