A Study of ELI-002 7P in Subjects With KRAS/NRAS Mutated Solid Tumors (AMPLIFY-7P)

First in Human Phase 1/2 Trial of ELI-002 7P Immunotherapy as Treatment for Subjects With Kirsten Rat Sarcoma (KRAS)/Neuroblastoma RAS Viral Oncogene Homolog (NRAS) Mutated Pancreatic Ductal Adenocarcinoma (PDAC) and Other Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Pancreatic Ductal Adenocarcinoma; KRAS G12D; KRAS G12R; NRAS G12D; NRAS G12R; KRAS G12V; KRAS G12C; KRAS G12A; KRAS G12S; KRAS G13D; NRAS G12V; NRAS G12C; NRAS G12S
• Intervention / Treatment: Drug: ELI-002 7P

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.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trial Inquiries; Phone Number: 617-714-9884; Email: clinicaltrialinquiries@elicio.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic Comprehensive Cancer Center
      • Principal Investigator: Tanios Bekaii-Saab, MD
      • Contact: Jacob Broach; Email: broach.jacob@mayo.edu
      • Contact: Rochelle Quinonez; Email: quinonez.rochelle@mayo.edu
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Contact: Vincent Chung, MD; Phone Number: 626-218-9200; Email: vchung@coh.org
      • Contact: Xiomara Anaya; Phone Number: 89782 626-218-9780
      • Principal Investigator: Vincent Chung, MD
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
      • Contact: Lisa Yonemoto; Phone Number: 16045 310-633-8400; Email: lyonemoto@mednet.ucla.edu
      • Principal Investigator: Zev Wainberg, MD
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine
      • Contact: Jennifer Valerin, MD, PhD
      • Contact: Phone Number: 877-827-8839; Email: ucstudy@uci.edu
      • Principal Investigator: Jennifer Valerin, MD, PhD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital-Anschutz Cancer Pavillion
      • Principal Investigator: Alexis Leal, MD
      • Contact: McKenna Russen; Phone Number: 303-724-9836; Email: mckenna.russen@cuanschutz.edu
  • Florida
    • Coral Gables, Florida, United States, 33124
      • Recruiting
      • University of Miami
      • Contact: Yolanda Justal; Email: yxj512@med.miami.edu
      • Contact: Peter J Hosein, MD; Email: phosein@med.miami.edu
      • Principal Investigator: Peter J Hosein, MD
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida Health Cancer Center
      • Contact: Ashley Gregorek; Phone Number: 352-265-5124
      • Contact: Email: Phase1@cancer.ufl.edu
      • Principal Investigator: Thomas George, MD, FACP
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Comprehensive Cancer Center
      • Principal Investigator: Umair Majeed, MBBS, MD
      • Contact: Qandeel Anwar; Email: anwar.qandeel@mayo.com
      • Contact: Jesse Vines; Phone Number: 904-953-4209; Email: vines.jesse@mayo.edu
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Lauren Ponto; Phone Number: 813-745-7658; Email: lauren.ponto@moffitt.org
      • Principal Investigator: DaeWon Kim, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Chandrikha Chandrasekaharan, MBBS; Email: chandrikha-chandrasekaharan@uiowa.edu
      • Principal Investigator: Chandrikha Chandrasekaharan, MBBS
  • Massachusetts
    • Boston, Massachusetts, United States, 02210
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Colin D Weekes, MD; Phone Number: 617-724-4000; Email: cdweekes@mgh.harvard.edu
      • Principal Investigator: Colin D Weekes, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Comprehensive Cancer Center
      • Contact: Preston Buechler; Phone Number: 507-422-5917; Email: buechler.preston@mayo.edu
      • Principal Investigator: Ryan Carr, MD
      • Contact: Ryan Car, MD; Email: carr.ryan@mayo.edu
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Northwell Health
      • Contact: Craig Devoe, MD; Phone Number: 516-734-8896; Email: cdevoe@northwell.edu
      • Contact: Email: ci-phasei_clinicaltrialsunit@northwell.edu
      • Principal Investigator: Craig Devoe, MD
    • New York, New York, United States, 10022
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Principal Investigator: Eileen O'Reilly, MD
      • Contact: Eileen M O'Reilly, MD; Phone Number: 646-888-4182
    • New York, New York, United States, 10065
      • Recruiting
      • New York Presbyterian Weill Cornell Medical Center
      • Contact: Casey Owens; Phone Number: 646-962-6046; Email: cdo4001@med.cornell.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Mark O'Hara, MD; Phone Number: 215-360-0919; Email: mark.ohara@pennmedicine.upenn.edu
      • Contact: Luda Mazaleuskaya; Phone Number: 1-267-455-9141; Email: mazali@pennmedicine.upenn.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
      • Contact: Clinical Trial Inquiries; Phone Number: 844-482-4812
      • Principal Investigator: Meredith Pelster, MD, MSCI
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern
      • Principal Investigator: Syed Kazmi, MD
      • Contact: Ellen Siglinsky; Phone Number: 214-645-9684; Email: ellen.siglinsky@utsouthwestern.edu
      • Contact: Pauline Phan; Phone Number: 214-852-0731; Email: pauline.phan@utsouthwestern.edu
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Email: GIClinicalTrials@mdanderson.org
      • Principal Investigator: Shubham Pant, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Principal Investigator: Ben George, MD
      • Contact: Colleen Cotter; Phone Number: 414-805-8839; Email: cmcotter@mcw.edu
      • Contact: Olivia Gorman; Phone Number: 414-805-6345; Email: ogorman@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Presence of tumor mutations where specific therapy is approved
• Known brain metastases
• Use of immunosuppressive drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1A: ELI-002 7P (Low Peptide dose); 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)	Drug: ELI-002 7P; ELI-002 Amph-CpG-7909 admixed with ELI-002 Amph-Peptides 7P administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections weekly for 4 weeks during the Booster Period (the two periods are separated by 2 months of no dosing)
Experimental: Phase 1A: ELI-002 7P (High Peptide dose); 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)	Drug: ELI-002 7P; ELI-002 Amph-CpG-7909 admixed with ELI-002 Amph-Peptides 7P administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections weekly for 4 weeks during the Booster Period (the two periods are separated by 2 months of no dosing)
Experimental: Phase 1B: 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)	Drug: ELI-002 7P; ELI-002 Amph-CpG-7909 admixed with ELI-002 Amph-Peptides 7P administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections weekly for 4 weeks during the Booster Period (the two periods are separated by 2 months of no dosing)
Experimental: Phase 2 randomized: 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)	Drug: ELI-002 7P; ELI-002 Amph-CpG-7909 admixed with ELI-002 Amph-Peptides 7P administered via SC injection weekly for 4 consecutive weeks, followed by bi-weekly injections over 4 weeks, during the Immunization Period; additional SC injections weekly for 4 weeks during the Booster Period (the two periods are separated by 2 months of no dosing)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Evaluate the safety 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	28 days after the first dose of ELI-002 7P
Phase 2: Compare ELI-002 7P versus standard of care (SOC; observation) in DFS (disease free survival)	DFS is assessed by the investigator through computed tomography (CT) imaging or magnetic resonance imaging (MRI) with contrast and using iRECIST criteria	After the last radiographic assessment at Visit 26 (Week 150)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and Phase 2: Determine the biomarker reduction or clearance rate	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	6 months
Phase 2: Evaluate the safety of ELI-002 7P	Safety will be assessed by the incidence of AEs and clinically significant laboratory tests and vital signs	30 days after the last ELI-002 7P dose
Phase 2: Determine the 1-year DFS	Compare between cohorts, ELI-002 7P vs Observation, the 1-year DFS	1 year
Phase 2: Determine the objective response rate (ORR) in subjects who crossover from Observation to ELI-002 7P treatment after confirmed progressive disease according to iRECIST	ORR is defined as the proportion of subjects achieving a complete response or partial response per iRECIST	After Visit 13 (Week 20)

Collaborators and Investigators

• Sponsor: Elicio Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: February 3, 2023
• First Submitted That Met QC Criteria: February 3, 2023
• First Posted (Actual): February 14, 2023

Study Record Updates

• Last Update Posted (Estimated): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Rectal cancer; Immunotherapy; Colon cancer; Adjuvant therapy; Colorectal cancer (CRC); Kirsten rat sarcoma (KRAS); Neuroblastoma ras viral oncogene homolog (NRAS); Pancreatic ductal adenocarcinoma (PDAC); Vaccine therapy; circulating tumor DNA (ctDNA); serum tumor biomarker; Carbohydrate antigen 19-9 (CA19-9); Carcinoembryonic antigen (CEA)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenocarcinoma
• Other Study ID Numbers: ELI-002-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No