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

Study Overview
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Brief Summary
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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.

Detailed Description
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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. The study 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. Additional cohorts may be added to explore intermediate or higher dose levels based on cumulative safety review and preliminary review of pharmcodynamic responses. 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.

Official Title
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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

Conditions
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Colorectal Cancer, Minimal Residual Disease, KRAS G12D, KRAS G12R, NRAS G12D, NRAS G12R, Pancreatic Ductal Adenocarcinoma, Non-small Cell Lung Cancer, Ovarian Cancer, Cholangiocarcinoma, Bile Duct Cancer, Gallbladder Carcinoma

Intervention / Treatment
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* Drug: ELI-002 2P


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ELI-002 2P Cohort 1<br>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<br>* 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)<br>|
| Experimental: ELI-002 2P Cohort 2<br>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<br>* 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)<br>|
| Experimental: ELI-002 2P Cohort 3<br>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<br>* 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)<br>|
| Experimental: ELI-002 2P Cohort 4<br>ELI-002 2P Amph-CpG-7909 (5.0 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<br>* 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)<br>|
| Experimental: ELI-002 2P Cohort 5<br>ELI-002 2P Amph-CpG-7909 (10.0 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<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the biomarker reduction and clearance rate | The ctDNA reduction and clearance rate is defined as the reduction or clearance of ctDNA , or if ctDNA was not detectable at baseline, serum tumor biomarker reduction or clearance compared to baseline. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Minimal residual disease (MRD), Kirsten rat sarcoma (KRAS), Neuroblastoma ras viral oncogene homolog (NRAS), Pancreatic ductal adenocarcinoma (PDAC), Colorectal cancer (CRC), Colon cancer, Rectal cancer, Non-small-cell lung cancer (NSCLC), Mucinous Ovarian cancer, Cholangiocarcinoma (CCA), Bile duct cancer, Gallbladder carcinoma, Immunotherapy, Vaccine therapy, Adjuvant therapy, circulating tumor DNA (ctDNA)