Clinical Trials /

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

NCT04853017

Description:

This is a Phase 1/2 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 tumor.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ELI-002 in Subjects With KRAS Mutated Pancreatic Ductal Adenocarcinoma (PDAC) and Other Solid Tumor
  • Official Title: First in Human Phase 1/2 Trial of ELI-002 Immunotherapy as Treatment for Subjects With Kirsten Rat Sarcoma (KRAS) Mutated Pancreatic Ductal Adenocarcinoma and Other Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ELI-002-001
  • NCT ID: NCT04853017

Conditions

  • 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

Interventions

DrugSynonymsArms
ELI-002 (Dose Escalation)ELI-002 (Phase 1A)
ELI-002 (at the RP2D)ELI-002 (Phase 1B)

Purpose

This is a Phase 1/2 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 tumor.

Detailed Description

      The study consists of 3 phases: Phase 1A, Phase 1B, and Phase 2. In Phase 1A, Amph modified
      KRAS peptides, Amph-G12D and Amph-G12R (ELI-002 2P) will be evaluated with admixed
      Amph-CpG-7909, with plans to transition to an Amph-Peptide 7P drug product containing all 7
      Amph-Peptides (G12D, G12R, G12V, G12A, G12C, G12S, G13D) for Phase 1B dose expansion and
      Phase 2 studies.

      The Phase 1A portion of the study is an open-label, dose-escalation, 3+3 design in which up
      to 18 subjects will be treated in 3 planned dose level cohorts. In this phase, 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.

      In Phase 1B, three dose expansion cohorts (up to 17 subjects in each cohort for a total of up
      to 51 subjects) will be added to evaluate for preliminary evidence of antitumor activity in
      KRAS and NRAS mutated solid tumors (including colorectal cancer, non-small cell lung cancer,
      mucinous ovarian cancer, as well as bile duct and gallbladder cancer) and changes from
      baseline in tumor biomarkers.

      In Phase 2, an additional 90 pancreatic cancer subjects will be randomized 2:1 (ELI-002
      versus observation) to further evaluate antitumor activity. Subjects randomized to ELI-002
      will receive subcutaneous (SC) injections of ELI-002 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 but will not
      receive ELI-002 treatment. Subjects randomized to observation will be able to cross-over to
      ELI-002 treatment in the event of confirmed disease progression.
    

Trial Arms

NameTypeDescriptionInterventions
ELI-002 (Phase 1A)ExperimentalDose escalation
  • ELI-002 (Dose Escalation)
ELI-002 (Phase 1B)ExperimentalDose expansion at RP2D
  • ELI-002 (at the RP2D)
ELI-002 or Observation (Phase 2, randomized)ExperimentalSubjects randomized to ELI-002 will receive ELI-002 at the RP2D. Subjects randomized to Observation will not receive ELI-002 intervention, however they will have the possibility to receive treatment following confirmed disease progression.
  • ELI-002 (at the RP2D)

Eligibility Criteria

        Inclusion Criteria:

          -  KRAS/NRAS mutated (G12D or G12R) solid tumor

          -  Positive for circulating tumor DNA 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1A: Determine the MTD of ELI-002 and the RP2D
Time Frame:28 days after first dose
Safety Issue:
Description:The MTD is defined as the highest dose level for which <33% of subjects had a dose-limiting toxicity.

Secondary Outcome Measures

Measure:Phase 1: Determine the ctDNA clearance rate
Time Frame:6 months
Safety Issue:
Description:The ctDNA clearance rate is defined as the proportion of subjects whose ctDNA status changes from positive at baseline to negative at 6 months.
Measure:Phase 2: Evaluate the safety of ELI-002
Time Frame:30 days after the last ELI-002 dose
Safety Issue:
Description:Safety will be assessed by the incidence of AEs and clinically significant laboratory tests and vital signs.
Measure:Phase 2: Determine the ctDNA clearance
Time Frame:6 months
Safety Issue:
Description:Compare between treatments, ELI-002 vs Observation, the proportion of subjects whose ctDNA status changes from positive at baseline to negative at 6 months.
Measure:Phase 2: Determine the 1-year RFS
Time Frame:1 year
Safety Issue:
Description:Compare between treatments, ELI-002 vs Observation, the 1-year RFS.
Measure:Phase 2: Determine the overall survival (OS)
Time Frame:24 months
Safety Issue:
Description:Compare between treatments, ELI-002 vs Observation, assuming proportional hazards, the OS (defined as the time from randomization to death).
Measure:Phase 2: Determine the objective response rate (ORR) in subjects who crossover from Observation to ELI-002 after confirmed relapse
Time Frame:After Visit 15 (Day 217)
Safety Issue:
Description:ORR is defined as the proportion of subjects achieving a complete response or a partial response per iRESIST.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Elicio Therapeutics

Trial 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

Last Updated

July 6, 2021