AMPLIFY-201: A Study of ELI-002 in Subjects With KRAS Mutated Pancreatic Ductal Adenocarcinoma (PDAC) and Other Solid Tumors

Sponsor

Elicio Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04853017

Collaborator

(none)

Enrollment

Locations

Arms

37.9

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1 study to assess the safety and efficacy of ELI-002 immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide [Amph-CpG-7909] plus a mixture of lipid-conjugated peptide-based antigens [Amph-Peptides]) as adjuvant treatment of minimal residual disease (MRD) in subjects with KRAS/neuroblastoma ras viral oncogene homolog (NRAS) mutated PDAC or other solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Minimal Residual Disease KRAS G12D KRAS G12R NRAS G12D NRAS G12R Pancreatic Ductal Adenocarcinoma Colorectal Cancer Non-small Cell Lung Cancer Ovarian Cancer Cholangiocarcinoma Bile Duct Cancer Gallbladder Carcinoma	Drug: ELI-002 2P	Phase 1

Detailed Description

This is a Phase 1 dose escalation study in which ELI-002 2P (Amph modified KRAS peptides, Amph-G12D and Amph-G12R admixed with admixed Amph-CpG-7909) will be evaluated, with plans to transition to the ELI-002 7P drug product containing all 7 Amph-Peptides (G12D, G12R, G12V, G12A, G12C, G12S, G13D) in future clinical trials.

This is an open-label, dose-escalation, 3+3 design in which approximately 18 subjects will be treated in 3 planned dose level cohorts. Increasing doses of Amph-CpG-7909 will be evaluated sequentially. Safety and pharmacodynamic data will be evaluated and a recommended Phase 2 dose (RP2D) will be determined in consideration of a maximum tolerated dose (MTD) if observed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

First in Human Phase 1 Trial of ELI-002 Immunotherapy as Treatment for Subjects With Kirsten Rat Sarcoma (KRAS) Mutated Pancreatic Ductal Adenocarcinoma and Other Solid Tumors

Actual Study Start Date :

Oct 4, 2021

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ELI-002 2P Cohort 1 ELI-002 2P Amph-CpG-7909 (0.1 mg) admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)	Drug: ELI-002 2P Amph-CpG-7909 admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)
Experimental: ELI-002 2P Cohort 2 ELI-002 2P Amph-CpG-7909 (0.5 mg) admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)	Drug: ELI-002 2P Amph-CpG-7909 admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)
Experimental: ELI-002 2P Cohort 3 ELI-002 2P Amph-CpG-7909 (2.5 mg) admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)	Drug: ELI-002 2P Amph-CpG-7909 admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)

Arm

Intervention/Treatment

Experimental: ELI-002 2P Cohort 1

ELI-002 2P Amph-CpG-7909 (0.1 mg) admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)

Drug: ELI-002 2P

Amph-CpG-7909 admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)

Experimental: ELI-002 2P Cohort 2

ELI-002 2P Amph-CpG-7909 (0.5 mg) admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)

Drug: ELI-002 2P

Experimental: ELI-002 2P Cohort 3

ELI-002 2P Amph-CpG-7909 (2.5 mg) admixed with Amph modified KRAS peptides (Amph-G12D and Amph-G12R) 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 consecutive weeks during the Booster Period (the two periods are separated by 3 months of no dosing)

Drug: ELI-002 2P

Outcome Measures

Primary Outcome Measures

Determine the MTD of ELI-002 and the RP2D [28 days after first dose]
The MTD is defined as the highest dose level for which <33% of subjects had a dose-limiting toxicity.
Evaluate the safety of ELI-002 [30 days after last dose]
Safety will be assessed by the incidence of adverse events (AEs) and clinically significant laboratory tests and vital signs.

Secondary Outcome Measures

Determine the circulating tumor DNA (ctDNA) reduction and clearance rate [6 months]
The ctDNA reduction and clearance rate is defined as the reduction or clearance of ctDNA compared to baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

KRAS/NRAS mutated (G12D or G12R) solid tumor
Positive for circulating tumor DNA (ctDNA) and/or elevated serum tumor biomarker 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, and the patient is able to receive the approved therapy
Known brain metastases
Use of immunosuppressive drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	University of California Los Angeles	Los Angeles	California	United States	90095
3	University of Colorado	Aurora	Colorado	United States	80045
4	University of Iowa	Iowa City	Iowa	United States	52242
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Henry Ford Cancer Institute	Detroit	Michigan	United States	48202
7	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
8	Northwell Health	Lake Success	New York	United States	11042
9	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
10	Tennessee Oncology - Centennial Clinic	Nashville	Tennessee	United States	37203
11	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030