Clinical trial NCT05726864: A Study of ELI-002 7P in Subjects With KRAS/NRAS Mutated Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreatic Ductal Adenocarcinoma
Colorectal Cancer
KRAS G12D
KRAS G12R
KRAS G12V
KRAS G12A
KRAS G12C
KRAS G12S
KRAS G13D
NRAS G12D
NRAS G12R
NRAS G12V
NRAS G12C
NRAS G12S
Keywords: Kirsten rat sarcoma (KRAS)
Neuroblastoma ras viral oncogene homolog (NRAS)
Pancreatic ductal adenocarcinoma (PDAC)
Colorectal cancer (CRC)
Colon cancer
Rectal cancer
Immunotherapy
Vaccine therapy
Adjuvant therapy
serum tumor biomarker
Carbohydrate antigen 19-9 (CA19-9)
Carcinoembryonic antigen (CEA)
circulating tumor DNA (ctDNA)
Lead sponsor: Elicio Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-02-14
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Evaluate the safety of ELI-002 7P
timeFrame: 28 days after the first dose of ELI-002 7P
measure: Phase 2: Compare ELI-002 7P versus standard of care (SOC; observation) in DFS (disease free survival)
timeFrame: After the last radiographic assessment at Visit 26 (Week 150)
Secondary outcomes:
measure: Phase 2: Overall Survival (OS)
timeFrame: After Visit 13 (Week 20)
measure: Phase 1 and Phase 2: Determine the biomarker reduction or clearance rate
timeFrame: 6 months
measure: Phase 2: Determine the 1-year DFS
timeFrame: 1 year
measure: Phase 2: Evaluate the safety of ELI-002 7P
timeFrame: 30 days after the last ELI-002 7P dose
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Comprehensive Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital-Anschutz Cancer Pavillion
state: Colorado
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Health
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Comprehensive Cancer Center
state: Minnesota
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Weill Cornell Medical Center
state: New York
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: