ELI-002 7P Phase 1 in Neoadjuvant PDAC: Rational Design, Sobering Precedent, Unproven Survival Path

Elicio Activates Phase 1 Neoadjuvant Study for ELI-002 7P in PDAC

Elicio Therapeutics has announced the activation of an investigator-initiated Phase 1 study (NCT07671339) evaluating ELI-002 7P for resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC). The study, conducted by Memorial Sloan Kettering Cancer Center and funded by The Lustgarten Foundation and Break Through Cancer, will assess ELI-002 7P in combination with chemotherapy and an anti-PD1 checkpoint inhibitor in the neoadjuvant setting. Expected to enroll 20 patients, the trial aims to generate clinical insights into ELI-002 7P's potential to improve surgical outcomes and long-term survival for patients with this devastating KRAS-driven disease.

• The newly activated randomized, open-label Phase 1 investigator-initiated trial will enroll 20 patients diagnosed with resectable or borderline resectable KRAS-mutant pancreatic ductal adenocarcinoma. Participants will receive ELI-002 7P alongside standard chemotherapy, mFOLFIRINOX, with or without the anti-PD1 checkpoint inhibitor tislelizumab, initiating treatment before surgery.
• This study builds upon previous observations of complete responses in patients with metastatic PDAC treated with sequential ELI-002 7P, checkpoint inhibitors, and chemotherapy. Researchers aim to prospectively evaluate this combination in the neoadjuvant setting, hoping to generate crucial clinical insights into ELI-002 7P's ability to reshape the tumor immune environment and enhance surgical outcomes and long-term survival.
• ELI-002 is Elicio's lead investigational AMP cancer immunotherapy, designed to target cancers driven by KRAS-gene mutations. The ELI-002 7P formulation is an off-the-shelf subcutaneous administration, engineered to provide immune response coverage against seven of the most common KRAS mutations, thereby broadening its potential applicability to a larger patient population.

The Persistent Challenge of Resectable KRAS-Mutant PDAC

Pancreatic ductal adenocarcinoma continues to present one of oncology's most intractable therapeutic challenges, with multiple high-priority unmet needs persisting despite incremental advances in systemic therapy. Distinct patient subpopulations have emerged as focal points for clinical investigation, each defined by disease stage, molecular profile, or prior treatment history.

• Borderline-Resectable and Locally-Advanced Disease: Patients with borderline-resectable (BRPC) and locally-advanced pancreatic cancer (LAPC) lack an agreed-upon standard of care, with no consensus on the optimal use of chemotherapy, radiation, or combination approaches in the neoadjuvant setting. The STEREOPAC trial is actively addressing this gap by evaluating neoadjuvant sequences combining modified FOLFIRINOX or gemcitabine/nab-paclitaxel with isotoxic high-dose stereotactic body radiation therapy.

• Homologous Recombination Deficiency (HRD)-Positive Patients: HRD-positive status — defined by BRCA1/2 biallelic loss-of-function and/or an HRD score ≥42 — identifies a molecularly distinct population (4.9% of patients) that derives substantial benefit from platinum-based adjuvant therapy, with a median PFS of 44.1 months versus 12.2 months in HRD-negative patients. This broader HRD definition meaningfully expands the eligible population beyond BRCA1/2 mutation carriers alone (1.9%).

• Chemotherapy-Refractory Unresectable Disease: Patients progressing on first-line gemcitabine plus nab-paclitaxel represent a population with very limited second-line options. The STNM01 trial evaluated stroma-modifying therapy combined with S-1 in this setting, reporting a median overall survival of 7.8 months and a disease control rate of 77.3%.

• Immune "Cold" Tumor Microenvironment: PDAC's dense immunosuppressive stroma, low tumor mutational burden, and minimal cytotoxic T-cell infiltration render it largely refractory to conventional immunotherapy approaches. Emerging strategies targeting this biology — including personalized mRNA neoantigen vaccines and mutant-KRAS–directed vaccines — have demonstrated sustained vaccine-induced T-cell responses associated with improved recurrence-free survival in the surgically resected setting.

• Treatment Sequencing in Metastatic Disease: There is currently no evidence-based guidance on the preferred sequencing of FOLFIRINOX versus gemcitabine/nab-paclitaxel. Data suggest that the overall survival advantage associated with first-line FOLFIRINOX is attenuated in patients receiving two or more lines of therapy (median OS 12.1 vs. 13.1 months), underscoring an unmet need for prospective sequencing strategies that preserve downstream therapeutic benefit.

Elicio's Neoadjuvant ELI-002 7P Study Design and Goals

Elicio Therapeutics' neoadjuvant ELI-002 7P program sits within a broader PDAC clinical trial landscape characterized by diverse study designs, ranging from phase I/II dose-escalation cohorts to large randomized phase III adjuvant trials. The table below summarizes key design parameters and endpoints across the most clinically relevant studies informing neoadjuvant and perioperative strategy in PDAC.

ELI-002 7P: A New Immunotherapy Front in Resectable PDAC

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging cancers to treat, with limited surgical eligibility and modest benefits from chemotherapy. For patients with resectable or borderline resectable disease, improving the chances of a complete surgical removal (R0 resection) and extending long-term survival are paramount. This is where neoadjuvant therapy, administered before surgery, plays a crucial role.

The initiation of a Phase 1 study for ELI-002 7P in this neoadjuvant setting represents a strategic move to address this high unmet need. ELI-002 is an amphiphile vaccine designed to target common KRAS mutations, which are key drivers in PDAC. Prior research with an earlier version, ELI-002 2P, demonstrated its ability to induce robust, persistent mKRAS-specific T cell responses and even antigen spreading, with these immune responses correlating with improved clinical outcomes in patients with minimal residual disease. This suggests a promising mechanism of action for stimulating the immune system against tumor cells.

However, the literature also highlights the challenges of cancer vaccine monotherapy in PDAC, often failing to outperform traditional treatments. This new study wisely incorporates a combination approach, pairing the mKRAS-specific vaccine with chemotherapy and an anti-PD1 checkpoint inhibitor. This multi-modal strategy is critical, as studies indicate that combining vaccines with immune checkpoint blockade is necessary to overcome the immune escape mechanisms prevalent in PDAC and enhance overall therapeutic responses. This approach aims to leverage the strengths of each modality: chemotherapy to reduce tumor burden, the vaccine to prime specific anti-tumor immunity, and the checkpoint inhibitor to release immune brakes.

While this Phase 1 study is small, its findings will be crucial. The primary risks include whether the observed immunologic responses translate into tangible improvements in R0 resection rates and long-term survival in this specific neoadjuvant population. Furthermore, the preliminary nature of a small Phase 1 trial means that even positive results will require extensive validation in larger, more diverse patient cohorts. Nevertheless, this trial signifies a significant step forward in exploring advanced immunotherapy combinations for a notoriously difficult cancer, potentially paving the way for more effective multidisciplinary approaches.