Elicio Therapeutics Reports Results from Phase 2 AMPLIFY-7P Study and Outlines Refined Phase 3 Development Strategy for ELI-002 7P in Adjuvant Pancreatic Cancer

Elicio Therapeutics Refines Phase 3 Strategy for ELI-002 7P After Phase 2 Results

Elicio Therapeutics reported results from its Phase 2 AMPLIFY-7P study of ELI-002 7P in adjuvant mKRAS-driven pancreatic cancer. The study did not meet its primary endpoint of disease-free survival (DFS) in the intent-to-treat population. However, post-hoc analyses revealed promising efficacy signals in patients with lower residual disease (R0 resected population), showing a significant DFS improvement (HR 0.65, p=0.048, n=121) and an absolute recurrence rate 9.5% lower at 18 months. Mutant KRAS-specific T cell responses also strongly correlated with improved DFS (HR 0.22, p<0.0001). These findings inform a refined Phase 3 development strategy focusing on R0 resected patients and additional dosing.

• The AMPLIFY-7P study, evaluating ELI-002 7P in adjuvant mKRAS-driven pancreatic cancer, did not achieve its pre-specified primary endpoint of disease-free survival (DFS) in the overall intent-to-treat population. However, landmark analyses indicated an early treatment benefit, with approximately 14% absolute DFS improvement during active treatment at 3 and 6 months. An imbalance in R1 resected patients (higher residual disease) in the ELI-002 7P arm, a known adverse prognostic factor, negatively impacted the overall results.
• Post-hoc analyses identified a stronger DFS hazard ratio of 0.65 (p=0.048) in the R0, completely resected patient population (n=121), representing 84% of the study participants. In this subgroup, ELI-002 7P demonstrated a median DFS of 23.8 months compared to 12.8 months for observation. Furthermore, mutant KRAS-specific T cell responses strongly correlated with improved DFS (HR 0.22, p<0.0001), validating the biological activity of ELI-002 7P.
• Based on the Phase 2 insights, Elicio Therapeutics has refined its Phase 3 development strategy to focus on R0 resected patients and incorporate additional ELI-002 7P dosing to enhance durability. The company plans a registrational study with DFS as the primary endpoint, aiming to address a significant unmet need in the adjuvant setting where no approved therapies currently exist. ELI-002 7P also exhibited a favorable safety and tolerability profile, with no treatment-related discontinuations or deaths, supporting potential longer-term administration.

AMPLIFY-7P: Decoding Phase 2 Results in Adjuvant mKRAS PDAC

Recent clinical and translational research in mutant KRAS-driven PDAC has yielded a growing body of evidence across both early-phase trials and preclinical combination strategies. The studies below span KRAS G12C and G12D inhibition, highlighting differential efficacy signals, tolerability profiles, and emerging resistance mechanisms.

• Glecirasib Pooled Analysis (NCT05009329 and NCT05002270): Two open-label Phase I/II trials evaluated glecirasib, an oral KRAS G12C inhibitor, in adult patients with KRAS G12C-mutant solid tumors. In a pooled analysis of 54 patients (data cutoff: June 30, 2024) — including 32 PDAC, 8 biliary tract cancers, 4 small intestinal cancers, 3 gastric cancers, 2 appendiceal cancers, and 5 other tumors — the confirmed ORR across 53 efficacy-evaluable patients was 50.9% (95% CI, 36.8%–64.9%). In the PDAC subgroup specifically, ORR was 46.9% (95% CI, 29.1%–65.3%), with a median PFS of 5.5 months and median OS of 10.8 months. TRAEs of any grade occurred in 94.4% of patients; grade ≥3 TRAEs were reported in 27.8%. Notably, no fatal TRAEs occurred and no TRAEs led to treatment discontinuation.

• HRS-4642 plus Nimotuzumab Trial (NCT06773130): This open-label, single-center, exploratory trial is evaluating the combination of HRS-4642 (a KRAS G12D inhibitor) and nimotuzumab (an EGFR inhibitor) in patients with recurrent/metastatic PDAC harboring the KRAS G12D mutation who have progressed on or are intolerant to first-line systemic therapy. Phase Ib initiates HRS-4642 at 1,200 mg Q2W with dose reductions to 1,000 mg or 800 mg Q2W for dose-limiting toxicities; nimotuzumab is dosed at 400 mg weekly. Phase Ib primary endpoints are safety characterization and RP2D determination, with secondary endpoints including ORR, PFS, OS, DCR, and DoR. Phase II employs a Simon's two-stage minimax design (~20 participants) with ORR as the primary endpoint.

• RNK08954 Phase 1a: This highly selective, orally bioavailable KRAS G12D inhibitor is distinguished by a unique pharmacokinetic profile and prolonged tumor tissue retention. Among 36 evaluable patients with a median follow-up of 4.85 months, the unconfirmed ORR in the 1,000–1,200 mg cohort of PDAC patients was 33.33%. Preclinical data also indicate synergy with immune checkpoint blockade, positioning RNK08954 as a candidate for combination investigation.

• MEK Inhibitor-Based Combinatorial Study (2022–2024): A retrospective/prospective single-institution observational study assessed MEKi-based combination regimens in 29 patients with metastatic PDAC harboring KRAS alterations — 34.5% G12R, 34.5% G12D, and 31% G12V. The majority received MEKi therapy in the third line or beyond. Median OS from MEKi initiation was 8.2 months (G12R), 5.1 months (G12D), and 4.7 months (G12V) (P=0.5); median PFS was 4.4, 2.3, and 1.4 months, respectively (P=0.11). Six patients (21%) discontinued at least one agent due to toxicity. MEKi-based regimens demonstrated modest disease control in KRAS G12R and minimal benefit in G12D/V in late-line settings.

• MRTX1133 Resistance Study: In vitro models of acquired resistance to MRTX1133, a first-in-class KRAS G12D inhibitor, revealed that drug-resistant PDAC cells undergo a global shift toward histone acetylation. BET inhibitors re-sensitized resistant cell lines to MRTX1133 and impaired FOSL1-mediated survival signaling in vitro. In murine models of MRTX1133-resistant PDAC, BET inhibition in combination with MRTX1133 markedly extended overall survival, establishing a mechanistic rationale for BET inhibitor co-administration to overcome acquired resistance.

• MDP5 plus MRTX1133 Nanoparticle Combination Study: MDP5, a dual BRD4/PI3K inhibitor, was co-loaded with MRTX1133 into MUC4-targeted polymeric nanoparticles (MRTX1133 loading: 8.3%; MDP5 loading: 7.4%) with pH-responsive release. In orthotopic PDAC models, the combination synergistically enhanced apoptosis and proliferation inhibition, outperforming both single-agent treatments and gemcitabine, without overt toxicity or detectable liver toxicity. Mechanistically, dual targeting reduced p-AKT and YAP1 levels, depleted CD44/ALDH cancer stem-like cells, and reprogrammed the tumor immune microenvironment by elevating CD8a and CD86 while reducing Ly-6G.

Charting ELI-002 7P's Phase 3 Path in R0 Resected PDAC

The clinical evidence base for mKRAS-driven PDAC spans retrospective real-world cohorts and early-phase investigational trials, collectively informing endpoint selection and patient stratification strategies for next-generation study designs. Across these studies, OS and PFS remain the anchor efficacy endpoints, with emerging data on treatment-specific hazard ratios by KRAS variant subtype providing granular prognostic resolution.

• Large-scale real-world cohort (2025): A retrospective analysis of 2,433 metastatic PDAC patients from a nationwide US clinicogenomic database (February 2010–September 2022) evaluated 2,023 KRAS-mutant patients for treatment outcomes. Primary endpoints were time-to-next-treatment (TTNT) and OS. KRAS G12D and G12V mutations were each associated with significantly higher risk of disease progression and death versus KRAS wild type (G12D: HR 1.15 for progression, HR 1.29 for death; G12V: HR 1.16 for progression, HR 1.23 for death). KRAS G12R patients demonstrated the most favorable outcomes, with median TTNT of 6.0 months and median OS of 13.2 months.

• Multicenter real-world profiling cohort (2024–2025): A retrospective analysis of 1,359 patients with early-stage (I–III) and metastatic PDAC enrolled via Perthera or PanCAN Know Your Tumor molecular profiling programs assessed OS and PFS from date of metastatic/recurrent diagnosis, stratified by KRAS variant and chemotherapy regimen. Cox regression was applied across first- and second-line settings, with subgroup comparisons referenced against G12D/V using a Bonferroni-adjusted significance threshold of α = 0.00714.

• Gemcitabine/nab-paclitaxel cohort (2022): A single-institution study of 110 unresectable PDAC patients receiving first-line gemcitabine plus nab-paclitaxel assessed KRAS status via quenching probe methodology on EUS-guided fine-needle aspiration specimens. Endpoints were PFS and OS; 15 patients were KRAS wild type. Wild-type KRAS was identified as an independent prognostic factor associated with significantly longer PFS and OS versus mutant KRAS (19.9 vs. 6.9 months and 11.8 vs. 5.3 months, respectively; HR 0.53, p = 0.045 and HR 0.35, p = 0.007).

• Cetuximab combination phase II trial (2011): Sixty-four patients with metastatic pancreatic cancer were enrolled in a multicenter phase II trial of cetuximab combined with gemcitabine and oxaliplatin until disease progression. KRAS mutational analysis was performed in 25 patients following microdissection; 14 of 25 (56%) harbored a codon 12 point mutation. Endpoints included PFS (104 days wild type vs. 118 days mutant) and OS (263 days wild type vs. 162 days mutant), with neither difference reaching statistical significance; presence of rash was significantly correlated with OS.

• TAK-981 (subasumstat) preclinical-to-translational evaluation (2024): The first-in-class SUMOylation inhibitor TAK-981 was assessed in KRAS-mutant cancer cell lines and mouse models. Monotherapy demonstrated modest efficacy; combination with trametinib (MEK inhibitor) dramatically induced apoptosis across multiple KRAS-mutant cell lines and gene-engineered mouse-derived organoids, producing long-term tumor regression. The mechanistic basis involved complementary inhibition of Rad51 and BRCA1 with consequent DNA damage accumulation, establishing a combinatorial rationale relevant to mKRAS PDAC trial design.

• Prognostic molecular subgroup study (2014): In a cohort of 153 PDAC patients, KRAS mutations in codon 12 or 13 were identified in 68% of cases by Sanger sequencing. KRAS mutational status was confirmed as an independent prognostic factor (p = 0.02); p53 expression, detected in 68% of 162 evaluable cases by immunohistochemistry on tissue microarrays, was not independently prognostic, and no correlation between KRAS mutational status and p53 expression was observed.

A Targeted Hope for Adjuvant mKRAS Pancreatic Cancer

Pancreatic cancer remains one of oncology's most formidable challenges, a disease where late diagnosis and aggressive biology often render curative surgery impossible and systemic therapies offer only modest survival gains. The recent Phase 2 AMPLIFY-7P study of ELI-002 7P, an immunotherapy targeting mKRAS-driven pancreatic cancer, initially presented a mixed picture, failing to meet its primary endpoint in the overall study population. However, a deeper dive into the data reveals a crucial silver lining that could reshape the therapeutic approach for a specific group of patients.

In a post-hoc analysis, patients who had undergone R0 resection—meaning all visible tumor was removed—showed a significant improvement in disease-free survival. This finding is particularly compelling because it suggests that in the setting of minimal residual disease, ELI-002 7P can effectively prime the immune system to prevent recurrence. The strong correlation between mutant KRAS-specific T cell responses and improved DFS further validates the drug's mechanism of action, highlighting the potential of neoantigen vaccines to harness the body's own defenses against cancer cells expressing these specific mutations. This also provides a valuable biomarker for identifying patients most likely to benefit and for monitoring treatment response.

This outcome points towards a strategic pivot for ELI-002 7P, focusing its Phase 3 development on this R0 resected adjuvant population. Such a precision medicine approach, while narrowing the target demographic, significantly increases the probability of demonstrating a clear clinical benefit in a disease desperately needing new options. However, risks remain. The reliance on a post-hoc subgroup analysis means these promising results require rigorous prospective validation. Pancreatic cancer's notoriously immunosuppressive microenvironment also presents an ongoing challenge, potentially limiting the long-term efficacy of any single agent. Nevertheless, by targeting a common oncogenic driver like KRAS and demonstrating immune activation linked to survival, ELI-002 7P offers a beacon of hope, potentially carving out a vital niche in the adjuvant treatment landscape for mKRAS-driven pancreatic cancer.