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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04956640
Collaborator
Loxo Oncology, Inc. (Industry), Merck Sharp & Dohme LLC (Industry)
360
22
2
27.4
16.4
0.6

Study Details

Study Description

Brief Summary

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. The study will last up to approximately 2 years.

Detailed Description

This is an open-label, multicenter Phase 1 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 2 parts, Part 1a is a dose escalation and Part 1b is a dose expansion. Part 1a will establish a recommended Phase 2 dose. Part 1b will have multiple arms of either monotherapy or in combination with other drugs.

KRAS G12C mutations will be identified through standard of care testing.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
360 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1a/1b Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors
Actual Study Start Date :
Jul 19, 2021
Anticipated Primary Completion Date :
Nov 1, 2023
Anticipated Study Completion Date :
Nov 1, 2023

Arms and Interventions

Arm Intervention/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

Drug: Abemaciclib
Oral
Other Names:
  • Verzenio
  • LY2835219
  • Drug: Erlotinib
    Oral
    Other Names:
  • Tarceva
  • Drug: Pembrolizumab
    Intravenous
    Other Names:
  • Keytruda
  • Drug: Temuterkib
    Oral
    Other Names:
  • LY3214996
  • Drug: LY3295668
    Oral

    Drug: Cetuximab
    Intravenous
    Other Names:
  • Erbitux
  • Drug: TNO155
    Oral

    Outcome Measures

    Primary Outcome Measures

    1. Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy [Cycle 1 (21 Days)]

      Measured by the number of patients with dose-limiting toxicities (DLTs)

    2. Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents [Cycle 1 (21 Days)]

      Measured by the number of patients with dose-limiting toxicities (DLTs)

    Secondary Outcome Measures

    1. To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR) [Estimated up to 2 years]

      ORR

    2. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR) [Estimated up to 2 years]

      DOR

    3. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR) [Estimated up to 2 years]

      BOR

    4. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR) [Estimated up to 2 years]

      TTR

    5. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR) [Estimated up to 2 years]

      DCR

    6. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS) [Estimated up to 2 years]

      PFS

    7. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS) [Estimated up to 2 years]

      OS

    8. To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC) [Predose estimated up to 2 years]

      PK: AUC of LY3537982

    9. To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax) [Predose estimated up to 2 years]

      PK: Cmax of LY3537982

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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).

    • Must be able to swallow capsule/tablet.

    • Agree and adhere to contraceptive use, if applicable.

    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.

    • Have symptomatic central nervous system (CNS) malignancy or metastasis and/or carcinomatous meningitis. Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids in excess of 10 milligrams (mg) per day prednisone/prednisolone (or equivalent) and their disease is asymptomatic and radiographically stable for at least 30 days.

    • Have received prior treatment with any KRAS G12C small molecule inhibitor, except in certain scenarios where such prior therapy is allowed as per protocol.

    • For Cohorts B2, B3, and B5/C1, patients treated with drugs known to be strong inhibitors or inducers of cytochrome P450 (CYP)3A.

    • The following patients will be excluded from Cohort B4:

    • 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.

    • The following patients will be excluded from Cohorts B7 & C3:

    • Clinically significant cardiac disease or risk factors at screening.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 USC Norris Cancer Hospital Los Angeles California United States 90033
    2 Chao Family Comprehensive Cancer Ctr. Orange California United States 92868
    3 Hoag Memorial Hospital Presbyterian Tustin California United States 92782
    4 Indiana Univ Melvin & Bren Simon Cancer Center Indianapolis Indiana United States 46202
    5 Community Health Network Indianapolis Indiana United States 46250
    6 Massachusetts General Hospital Boston Massachusetts United States 02114
    7 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    8 NYU Langone Health- Long Island Mineola New York United States 11501
    9 NYU Langone Medical Center- Perlmutter Cancer Center (NYU Cancer Institute) New York New York United States 10016
    10 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    11 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
    12 Vanderbilt Univeristy School of Medicine Nashville Tennessee United States 37212-6303
    13 South Texas Accelerated Research Therapeutics, LLC San Antonio Texas United States 78229-3307
    14 START Mountain Region West Valley City Utah United States 84119
    15 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    16 University of Wisconsin-Madison Hospital and Health Clinic Madison Wisconsin United States 53792-4108
    17 St Vincent's Hospital Sydney Sydney New South Wales Australia 2010
    18 Alberta Health Services Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    19 Aichi Cancer Center Hospital Nagoya Aichi Japan 464-8681
    20 National Cancer Center Hospital East Kashiwa Chiba Japan 277-8577
    21 National Cancer Center Hospital Chuo-ku Tokyo Japan 104-0045
    22 National Cancer Center Goyang-si Gyeonggi-do Korea, Republic of 10408

    Sponsors and Collaborators

    • Eli Lilly and Company
    • Loxo Oncology, Inc.
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Melinda Willard, PhD, Loxo Oncology, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT04956640
    Other Study ID Numbers:
    • LOXO-RAS-20001
    • 2021-000595-12
    • J3M-OX-JZQA
    • KEYNOTE E27
    First Posted:
    Jul 9, 2021
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 26, 2022