A Study of ELI-002 7P in Subjects With KRAS/NRAS Mutated Solid Tumors
- Conditions
- KRAS G12DKRAS G12CNRAS G12RNRAS G12VPancreatic Ductal AdenocarcinomaColorectal CancerNRAS G12DNRAS G12SKRAS G12RKRAS G12A
- Interventions
- Registration Number
- NCT05726864
- Lead Sponsor
- Elicio Therapeutics
- Brief Summary
This is a Phase 1/2 study to assess the safety and efficacy of ELI-002 7P immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide \[Amph-CpG-7909\] plus a mixture of lipid-conjugated peptide-based antigens \[Amph-Peptides 7P\]) as adjuvant treatment in subjects with solid tumors with mutated KRAS/NRAS. This study builds on the experience obtained with related product ELI-002 2P, which was studied in protocol ELI-002-001 under IND 26909.
- Detailed Description
The study consists of 3 phases: Phase 1A, Phase 1B, and Phase 2. In Phase 1A, seven Amph modified KRAS and NRAS peptides, G12D, G12R, G12V, G12A, G12C, G12S, G13D (Amph-Peptides 7P) will be evaluated in combination with recommended Phase 2 dose of Amph-CpG-7909 (10.0mg). This Amph-CpG-7909 dose will be evaluated with two Amph-Peptides 7P dose levels (1.4mg and 4.9mg) in 6 subjects per dose level. Following enrollment of these 12 subjects, the independent data monitoring committee (IDMC) will decide if another 6 subjects should be enrolled or if the dose can be determined for Phase 1B and Phase 2 portions of the study to be opened. If another 6 subjects are enrolled to Phase 1A, the IDMC will meet again to decide upon the dose for Phase 1B and Phase 2 prior to opening these portions of the study.
In Phase 1B, one dose expansion cohort of up to 17 colorectal cancer \[CRC\] subjects may be added to evaluate for preliminary evidence of biomarker response, including circulating tumor deoxyribonucleic acid (ctDNA) and/or serum tumor biomarker (such as CA19-9 and CEA) reduction and clearance in KRAS and NRAS.
In Phase 2, an additional 135 PDAC subjects will be randomized 2:1 (ELI-002 7P versus observation) to further evaluate antitumor activity. Subjects randomized to ELI-002 7P will receive subcutaneous (SC) injections of ELI-002 7P during Immunization and Booster Periods. Subjects randomized to observation will have the same safety and efficacy evaluations and will follow the same assessment schedule as subjects randomized to ELI-002 7P but will not receive study treatment. Subjects randomized to observation will be able to elect to cross-over to ELI-002 7P treatment in the event of confirmed disease progression.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 158
- KRAS/NRAS mutated (G12D, G12R, G12V, G12A, G12C, G12S, G13D) solid tumor
- Phase 1 only: positive for circulating tumor DNA and/or elevated serum tumor biomarkers (such as CA19-9 and CEA) despite prior standard therapy including surgery and chemotherapy/radiation therapy where applicable
- Screening CT is negative for recurrent disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Presence of tumor mutations where specific therapy is approved
- Known brain metastases
- Use of immunosuppressive drugs
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1A: ELI-002 7P (Low Peptide dose) ELI-002 7P ELI-002 Amph-CpG-7909 (10.0mg) admixed with ELI-002 Amph-Peptides 7P (1.4mg) administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections for 4 consecutive weeks during the Booster Period (the two periods are separated by 2 months of no dosing) Phase 1B: ELI-002 7P ELI-002 7P The ELI-002 7P dose selected during the Phase 1A portion of the study will be administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections for 4 consecutive weeks during the Booster Period (the two periods are separated by 2 months of no dosing) Phase 1A: ELI-002 7P (High Peptide dose) ELI-002 7P ELI-002 Amph-CpG-7909 (10.0mg) admixed with ELI-002 Amph-Peptides 7P (4.9mg) administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections for 4 consecutive weeks during the Booster Period (the two periods are separated by 2 months of no dosing) Phase 2 randomized: ELI-002 7P ELI-002 7P The ELI-002 7P dose selected during the Phase 1A portion of the study will be administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections for 4 consecutive weeks during the Booster Period (the two periods are separated by 2 months of no dosing)
- Primary Outcome Measures
Name Time Method Phase 1: Evaluate the safety of ELI-002 7P 28 days after the first dose of ELI-002 7P Safety will be assessed by the incidence of adverse events (AEs) and clinically significant changes in laboratory tests and vital signs
Phase 2: Compare ELI-002 7P versus standard of care (SOC; observation) in DFS (disease free survival) After the last radiographic assessment at Visit 26 (Week 150) DFS is assessed by the investigator through computed tomography (CT) imaging or magnetic resonance imaging (MRI) with contrast and using iRECIST criteria
- Secondary Outcome Measures
Name Time Method Phase 2: Overall Survival (OS) After Visit 13 (Week 20) To compare OS between cohorts, ELI-002 7P vs Observation
Phase 1 and Phase 2: Determine the biomarker reduction or clearance rate 6 months The ctDNA reduction or clearance is defined as reduction or clearance of ctDNA from baseline, or if ctDNA was not detectable at baseline, serum tumor biomarker (such as CA19-9 and CEA) reduction and clearance compared to baseline
Phase 2: Determine the 1-year DFS 1 year Compare between cohorts, ELI-002 7P vs Observation, the 1-year DFS
Phase 2: Evaluate the safety of ELI-002 7P 30 days after the last ELI-002 7P dose Safety will be assessed by the incidence of AEs and clinically significant laboratory tests and vital signs
Trial Locations
- Locations (26)
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic Comprehensive Cancer Center
🇺🇸Rochester, Minnesota, United States
City of Hope
🇺🇸Duarte, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University of California, Irvine
🇺🇸Orange, California, United States
University of Colorado Hospital-Anschutz Cancer Pavillion
🇺🇸Aurora, Colorado, United States
University of Miami
🇺🇸Coral Gables, Florida, United States
University of Florida Health Cancer Center
🇺🇸Gainesville, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Emory Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Ochsner Health
🇺🇸New Orleans, Louisiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Northwell Health
🇺🇸Lake Success, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
New York Presbyterian Weill Cornell Medical Center
🇺🇸New York, New York, United States
Lehigh Valley Health Network
🇺🇸Allentown, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States