3 Key Takeaways
Plain English Summary- 01Core Finding
In the Phase 2 AMPLIFY-7P trial, patients with stage I-III KRAS-mutated PDAC without recurrence within 6 months of standard therapy were randomized 2:1 to camupepimut (n = 96) or standard-of-care/observation (n = 48).
- 02Study Evidence
Tested in a randomized controlled trial (n = 96) at the Phase III stage.
- 03Practical Meaning
These efficacy (real-world effectiveness in the trial) and immunogenicity signals will inform a refined strategy for a confirmatory Phase 3 trial.
What This Means for You
Exploratory analysis demonstrated that ex vivo mKRAS-specific T cell responses were robust (a clinically meaningful level, 89/90) and associated with antigen spreading (a clinically meaningful level, 13/15). In camupepimut-treated patients, mKRAS-specific T cell response >9.17-fold over baseline (a clinically meaningful level, 74/90) correlated with improved DFS (HR 0.22, P < 0.0001), with the median DFS not reached versus 6.08 months for above and below 9.17-fold, respectively. Camupepimut safety was similar to observation, with grade ≥3 adverse events in a clinically meaningful level (10/96) versus a clinically meaningful level (7/48), and few serious AEs (a clinically meaningful level, 6/96 versus a clinically meaningful level, 4/48; reflecting progression/surgical complication). These efficacy (real-world effectiveness in the trial) and immunogenicity signals will inform a refined strategy for a confirmatory Phase 3 trial. ClinicalTrials.gov identifier: NCT05726864.
The Discovery
Camupepimut (ELI-002 7P) drives mutated KRAS (mKRAS)-specific T cell responses that correlated with disease-free survival (DFS) and overall survival (OS) in patients with mKRAS pancreatic adenocarcinoma (PDAC) in the Phase 1 AMPLIFY-201 trial. In the Phase 2 AMPLIFY-7P trial, patients with stage I-III KRAS-mutated PDAC without recurrence within 6 months of standard therapy were randomized 2:1 to camupepimut (n = 96) or standard-of-care/observation (n = 48). Stratification balanced nodal status. The primary DFS endpoint was not met (median 23.8 versus 21.2 months; HR 0.85, P = 0.5329). However, prespecified and exploratory analyses were informative. A numerical DFS advantage at 6 months of 14.0% (75.7% versus 61.7%; HR 0.55, P = 0.0557) corresponded to camupepimut dosing. Post hoc multivariate Cox regression analysis of DFS indicated an improved outcome for camupepimut (adjusted HR 0.47, P = 0.0086), a worse outcome for stage III disease (adjusted HR 2.29, P = 0.0127), an elevated baseline CA19-9 (adjusted HR 3.16, P < 0.0001) and baseline circulating tumor DNA (ctDNA) positivity (adjusted HR 5.99, P < 0.0001). Prespecified subgroup analyses addressing prognostic and predictive factors suggested DFS benefit for camupepimut (ctDNA negative: HR 0.51, P = 0.0280; no prior radiation: HR 0.59, P = 0.0221). Exploratory analysis demonstrated that ex vivo mKRAS-specific T cell responses were robust (a clinically meaningful level, 89/90) and associated with antigen spreading (a clinically meaningful level, 13/15).
How It Works, Simply
This infectious disease research focuses on T cells · Immune response · Genetics. Researchers evaluated it using a randomized controlled trial (n = 96) at the Phase III stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
In the Phase 2 AMPLIFY-7P trial, patients with stage I-III KRAS-mutated PDAC without recurrence within 6 months of standard therapy were randomized 2:1 to camupepimut (n = 96) or standard-of-care/observation (n = 48).
- 02Study Evidence
Tested in a randomized controlled trial (n = 96) at the Phase III stage.
- 03Practical Meaning
These efficacy and immunogenicity signals will inform a refined strategy for a confirmatory Phase 3 trial.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (n = 96) · Phase III
Biological Pathway & Modality
T cells · Immune response · Genetics
Intervention: Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic cancer: the
Experimental Findings & Endpoints
Camupepimut (ELI-002 7P) drives mutated KRAS (mKRAS)-specific T cell responses that correlated with disease-free survival (DFS) and overall survival (OS) in patients with mKRAS pancreatic adenocarcinoma (PDAC) in the Phase 1 AMPLIFY-201 trial.
In the Phase 2 AMPLIFY-7P trial, patients with stage I-III KRAS-mutated PDAC without recurrence within 6 months of standard therapy were randomized 2:1 to camupepimut (n = 96) or standard-of-care/observation (n = 48). Stratification balanced nodal status.
The primary DFS endpoint was not met (median 23.8 versus 21.2 months; HR 0.85, P = 0.5329). However, prespecified and exploratory analyses were informative.
A numerical DFS advantage at 6 months of 14.0% (75.7% versus 61.7%; HR 0.55, P = 0.0557) corresponded to camupepimut dosing. Post hoc multivariate Cox regression analysis of DFS indicated an improved outcome for camupepimut (adjusted HR 0.47, P = 0.0086), a worse outcome for stage III disease (adjusted HR 2.29, P = 0.0127), an elevated baseline CA19-9 (adjusted HR 3.16, P < 0.0001) and baseline circulating tumor DNA (ctDNA) positivity (adjusted HR 5.99, P < 0.0001).
Prespecified subgroup analyses addressing prognostic and predictive factors suggested DFS benefit for camupepimut (ctDNA negative: HR 0.51, P = 0.0280; no prior radiation: HR 0.59, P = 0.0221). Exploratory analysis demonstrated that ex vivo mKRAS-specific T cell responses were robust (a clinically meaningful level, 89/90) and associated with antigen spreading (a clinically meaningful level, 13/15).
Clinical Translation & Practice Context
Exploratory analysis demonstrated that ex vivo mKRAS-specific T cell responses were robust (a clinically meaningful level, 89/90) and associated with antigen spreading (a clinically meaningful level, 13/15).
In camupepimut-treated patients, mKRAS-specific T cell response >9.17-fold over baseline (a clinically meaningful level, 74/90) correlated with improved DFS (HR 0.22, P < 0.0001), with the median DFS not reached versus 6.08 months for above and below 9.17-fold, respectively. Camupepimut safety was similar to observation, with grade ≥3 adverse events in a clinically meaningful level (10/96) versus a clinically meaningful level (7/48), and few serious AEs (a clinically meaningful level, 6/96 versus a clinically meaningful level, 4/48; reflecting progression/surgical complication).
These efficacy and immunogenicity signals will inform a refined strategy for a confirmatory Phase 3 trial. ClinicalTrials.gov identifier: NCT05726864.
The Bottom Line · Clinical Pearl
“ClinicalTrials.gov identifier: NCT05726864 .”
Published in Nature Medicine · Current Stage: Phase III