Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)

PHASE1PHASE2RECRUITING

The purpose of this study is to find out whether the study drug, LY3537982, is safe and effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must have already received or were not able to tolerate the standard of care, except for specific groups who have not had cancer treatment. The study will last up to approximately 4 years.

info
Simpliy with AI

Study details:

This is an open-label, multicenter Phase 1/2 study to evaluate safety, tolerability, and preliminary efficacy of oral LY3537982 in patients with KRAS G12C-mutant solid tumors. This study will be conducted in 4 parts: Phase 1a dose escalation, Phase 1b dose expansion, Phase 1b dose optimization, and Phase 2. KRAS G12C mutations will be identified through standard of care testing.

info
Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Patients have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
  • Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or circulating tumor deoxyribonucleic acid (DNA).
  • Participants must have a histological or a cytologically proven diagnosis of locally advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Have adequate organ function.
  • Have discontinued all previous treatments for cancer with resolution of any significant ongoing adverse events (AEs), (except in certain scenarios).
  • Must be able to swallow capsule/tablet.
  • Agree and adhere to contraceptive use, if applicable.
  • For some parts of the study, (i.e., one of the two arms with LY3537982 in combination with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic setting and not suitable for curative intent radical surgery or radiation therapy. Previously untreated patients who received adjuvant and neoadjuvant therapy are eligible if the last dose of the systemic treatment was completed at least 6 months prior to enrollment. For untreated patients in the arm with LY3537982 in combination with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of any or all of the drugs other than LY3537982 may be initiated within 21 days prior to enrollment. Start of study treatment may be delayed to allow sufficient time for recovery from treatment-related toxicity.
  • For one part of the study, participants must have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.
  • Exclusion criteria

  • Disease suitable for local therapy administered with curative intent.
  • Have an active, ongoing, or untreated infection.
  • Have a serious pre-existing medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
  • Have a serious cardiac condition.
  • Have a second active primary malignancy or have been diagnosed and/or treated for an additional malignancy within 3 years prior to enrollment.
  • For some parts of the study only: have untreated active central nervous system (CNS) metastases and/or leptomeningeal disease. Patients with treated CNS metastases are eligible for this study if their disease is asymptomatic, radiographically stable for at least 30 days, and they do not require treatment with steroids in the two-week period prior to study treatment. Patients with active CNS metastases are eligible for one part of the study.
  • Have received prior treatment with any KRAS G12C small molecule inhibitor, except in certain scenarios where such prior therapy is allowed as per protocol.
  • The following patients will be excluded from some parts of the study: Experienced certain serious side effects with prior immunotherapy.
  • Have an active autoimmune disease that has required systemic anti-autoimmune treatment in the past 2 years.
  • Have received a live vaccine within 30 days prior to the first dose of study drug.
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 180 days after the last dose of study medication.
  • Known allergic reaction against any of the components of the study treatments.
  • info
    Simplify with AI

    Eligibility

    Age eligible for study : 18 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2021-07-19

    Primary completion: 2026-06-01

    Study completion finish: 2026-06-01

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

      PHASE2

    trial

    Trial ID

    NCT04956640

    Intervention or treatment

    DRUG: LY3537982

    DRUG: Pembrolizumab

    DRUG: Cetuximab

    DRUG: Pemetrexed

    DRUG: Cisplatin

    DRUG: Carboplatin

    Conditions

    • Carcinoma, Non-Small-Cell Lung
    • Colorectal Neoplasms
    • Endometrial Neoplasms
    • Ovarian Neoplasms
    • Pancreatic Neoplasms
    • Biliary Tract Neoplasms
    Image related to Carcinoma, Non-Small-Cell Lung
    • Condition: Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms and more

    • DRUG: LY3537982 and other drugs

    • St Leonards, New South Wales, Australia and more

    • Sponsor: Eli Lilly and Company

    Find a site

    Closest Location:

    Royal North Shore Hospital

    Research sites nearby

    Select from list below to view details:

    • Royal North Shore Hospital

      St Leonards, New South Wales, Australia

    • Cancer Research SA

      Adelaide, South Australia, Australia

    • Linear Clinical Research

      Nedlands, Western Australia, Australia

    • St Vincent's Hospital Sydney

      Sydney, New South Wales, Australia

    Loading...

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: LY3537982 (Dose Escalation)
    • LY3537982 administered orally.
    DRUG: LY3537982
    • Oral
    EXPERIMENTAL: LY3537982 (Dose Expansion)
    • LY3537982 administered orally either alone or with another investigational agent.
    DRUG: LY3537982
    • Oral
    EXPERIMENTAL: LY3537982 (Dose Optimization)
    • LY3537982 administered orally either alone or with another investigational agent
    DRUG: LY3537982
    • Oral

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapyMeasured by the number of patients with dose-limiting toxicities (DLTs)Cycle 1 (21 Days)
    Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agentsMeasured by the number of patients with dose-limiting toxicities (DLTs)Cycle 1 (21 Days)
    Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumabMeasured by TEAEsEstimated up to 2 years
    To determine the optimal dose of LY3537982 to be administered to participants who have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC in combination with cetuximabNot SpecifiedEstimated up to 2 years
    To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutationNot SpecifiedEstimated up to 2 years

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)ORREstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR)DOREstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR)BOREstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR)TTREstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)DCREstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS)PFSEstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS)OSEstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Intracranial DOR based on modified RECIST v1.1 (Certain arms of the study only)Intracranial DOREstimated up to 2 years
    To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Whole-body ORR based on RECIST v1.1 and modified RECIST v1.1 (Certain arms of the study only)Whole-body ORREstimated up to 2 years
    To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)PK: AUC of LY3537982Predose estimated up to 2 years
    To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)PK: Cmax of LY3537982Predose estimated up to 2 years

    Frequently Asked Questions

    Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

    No questions submitted. Be the first to ask a question!

    You may be eligible to participate in this trial based on your search.Apply for study
    Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

    References

    Clinical Trials Gov: Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)

    Other trails to consider

    Top searched conditions