Bile Duct Cancer, Cholangiocarcinoma, Colorectal Cancer, Gallbladder Carcinoma, KRAS G12D, KRAS G12R, Minimal Residual Disease, Non-small Cell Lung Cancer, NRAS G12D, NRAS G12R, Ovarian Cancer, Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
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)
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.
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. 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 pharmacodynamic 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.
Interventions
DRUGELI-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)
Sponsors
Elicio Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Participant Incidence of Treatment-emergent Adverse Events Considered by the Investigator as Related to ELI-002 | Adverse events were collected through 28 days after the last dose | The safety of ELI-002 was monitored through adverse events, including those considered related to treatment by the investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Participants With Biomarker Reduction | 6 months | A biomarker reduction was any decrease from baseline in circulating tumor DNA (ctDNA) and/or serum tumor antigen levels (carbohydrate antigen 19-9 \[CA19-9\] or carcinoembryonic antigen \[CEA\]). |
| The Proportion of Participants With Biomarker Clearance | 6 months | Biomarker clearance was defined as no detectable ctDNA, CA19-9, or CEA at post-treatment time points. |
| The Proportion of Participants With Biomarker Reduction by Biomarker Type | 6 months | A biomarker reduction was any decrease from baseline in ctDNA and/or serum tumor antigen levels (CA19-9 or CEA). |
| The Proportion of Participants With Biomarker Clearance by Biomarker Type | 6 months | Biomarker clearance was defined as no detectable ctDNA, CA19-9, or CEA at post-treatment time points |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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)
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) | 3 |
| 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)
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) | 6 |
| 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)
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) | 5 |
| ELI-002 2P Cohort 4 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)
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) | 5 |
| ELI-002 2P Cohort 5 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)
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) | 6 |
| Total | 25 |
Baseline characteristics
| Characteristic | ELI-002 2P Cohort 2 | Total | ELI-002 2P Cohort 5 | ELI-002 2P Cohort 4 | ELI-002 2P Cohort 1 | ELI-002 2P Cohort 3 |
|---|---|---|---|---|---|---|
| Age, Continuous | 54.5 years | 61.0 years | 59.0 years | 67.0 years | 50.0 years | 67.0 years |
| Disease stage at screening Stage I, II | 2 Participants | 8 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Disease stage at screening Stage III, IV | 4 Participants | 17 Participants | 5 Participants | 4 Participants | 2 Participants | 2 Participants |
| Pancreatic ductal adenocarcinoma diagnosis | 4 Participants | 20 Participants | 6 Participants | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 21 Participants | 5 Participants | 5 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 6 participants | 25 participants | 6 participants | 5 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 5 Participants | 15 Participants | 1 Participants | 3 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 10 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 5 / 6 | 4 / 5 | 4 / 5 | 5 / 6 |
| serious Total, serious adverse events | 1 / 3 | 0 / 6 | 0 / 5 | 0 / 5 | 1 / 6 |
Outcome results
Primary
The Participant Incidence of Treatment-emergent Adverse Events Considered by the Investigator as Related to ELI-002
The safety of ELI-002 was monitored through adverse events, including those considered related to treatment by the investigator
Time frame: Adverse events were collected through 28 days after the last dose
Population: All enrolled subjects were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELI-002 2P Cohort 1 | The Participant Incidence of Treatment-emergent Adverse Events Considered by the Investigator as Related to ELI-002 | 1 Participants |
| ELI-002 2P Cohort 2 | The Participant Incidence of Treatment-emergent Adverse Events Considered by the Investigator as Related to ELI-002 | 3 Participants |
| ELI-002 2P Cohort 3 | The Participant Incidence of Treatment-emergent Adverse Events Considered by the Investigator as Related to ELI-002 | 2 Participants |
| ELI-002 2P Cohort 4 | The Participant Incidence of Treatment-emergent Adverse Events Considered by the Investigator as Related to ELI-002 | 2 Participants |
| ELI-002 2P Cohort 5 | The Participant Incidence of Treatment-emergent Adverse Events Considered by the Investigator as Related to ELI-002 | 4 Participants |
Secondary
The Proportion of Participants With Biomarker Clearance
Biomarker clearance was defined as no detectable ctDNA, CA19-9, or CEA at post-treatment time points.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELI-002 2P Cohort 1 | The Proportion of Participants With Biomarker Clearance | 1 Participants |
| ELI-002 2P Cohort 2 | The Proportion of Participants With Biomarker Clearance | 2 Participants |
| ELI-002 2P Cohort 3 | The Proportion of Participants With Biomarker Clearance | 1 Participants |
| ELI-002 2P Cohort 4 | The Proportion of Participants With Biomarker Clearance | 1 Participants |
| ELI-002 2P Cohort 5 | The Proportion of Participants With Biomarker Clearance | 1 Participants |
Secondary
The Proportion of Participants With Biomarker Clearance by Biomarker Type
Biomarker clearance was defined as no detectable ctDNA, CA19-9, or CEA at post-treatment time points
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELI-002 2P Cohort 1 | The Proportion of Participants With Biomarker Clearance by Biomarker Type | 6 Participants |
| ELI-002 2P Cohort 2 | The Proportion of Participants With Biomarker Clearance by Biomarker Type | 0 Participants |
Secondary
The Proportion of Participants With Biomarker Reduction
A biomarker reduction was any decrease from baseline in circulating tumor DNA (ctDNA) and/or serum tumor antigen levels (carbohydrate antigen 19-9 \[CA19-9\] or carcinoembryonic antigen \[CEA\]).
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELI-002 2P Cohort 1 | The Proportion of Participants With Biomarker Reduction | 2 Participants |
| ELI-002 2P Cohort 2 | The Proportion of Participants With Biomarker Reduction | 5 Participants |
| ELI-002 2P Cohort 3 | The Proportion of Participants With Biomarker Reduction | 4 Participants |
| ELI-002 2P Cohort 4 | The Proportion of Participants With Biomarker Reduction | 4 Participants |
| ELI-002 2P Cohort 5 | The Proportion of Participants With Biomarker Reduction | 6 Participants |
Secondary
The Proportion of Participants With Biomarker Reduction by Biomarker Type
A biomarker reduction was any decrease from baseline in ctDNA and/or serum tumor antigen levels (CA19-9 or CEA).
Time frame: 6 months
Population: All enrolled subject by biomarker type at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ELI-002 2P Cohort 1 | The Proportion of Participants With Biomarker Reduction by Biomarker Type | 12 Participants |
| ELI-002 2P Cohort 2 | The Proportion of Participants With Biomarker Reduction by Biomarker Type | 9 Participants |