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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04956640
Recruitment Status : Recruiting
First Posted : July 9, 2021
Last Update Posted : January 12, 2024
Sponsor:
Collaborators:
Loxo Oncology, Inc.
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Eli Lilly and Company

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, except for specific groups who have not had cancer treatment. The study will last up to approximately 4 years.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Endometrial Neoplasms Ovarian Neoplasms Pancreatic Neoplasms Biliary Tract Neoplasms Drug: LY3537982 Drug: Pembrolizumab Drug: Cetuximab Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin Phase 1 Phase 2

Detailed Description:

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 3 parts: Phase 1a dose escalation, Phase 1b dose expansion and dose optimization, and Phase 2.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors
Actual Study Start Date : July 19, 2021
Estimated Primary Completion Date : September 2025
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine


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: Pembrolizumab
Intravenous
Other Name: Keytruda

Drug: Cetuximab
Intravenous
Other Name: Erbitux

Drug: Pemetrexed
Intravenous
Other Names:
  • LY231514
  • Alimta

Drug: Cisplatin
Intravenous

Drug: Carboplatin
Intravenous




Primary Outcome Measures :
  1. Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy [ Time Frame: 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 [ Time Frame: Cycle 1 (21 Days) ]
    Measured by the number of patients with dose-limiting toxicities (DLTs)

  3. Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab [ Time Frame: Estimated up to 2 years ]
    Measured by TEAEs

  4. 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 cetuximab [ Time Frame: Estimated up to 2 years ]
  5. To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation [ Time Frame: Estimated up to 2 years ]

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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Estimated up to 2 years ]
    OS

  8. To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Intracranial ORR based on modified RECIST v1.1 (Certain arms of the study only) [ Time Frame: Estimated up to 2 years ]
    Intracranial ORR

  9. 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) [ Time Frame: Estimated up to 2 years ]
    Intracranial DOR

  10. 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) [ Time Frame: Estimated up to 2 years ]
    Whole-body ORR

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

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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • Have symptomatic central nervous system (CNS) malignancy or metastasis and/or carcinomatous meningitis. 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. This only applies to some parts 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04956640


Contacts
Layout table for location contacts
Contact: Patient Advocacy 855-569-6305 clinicaltrials@loxooncology.com

Locations
Show Show 45 study locations
Sponsors and Collaborators
Eli Lilly and Company
Loxo Oncology, Inc.
Merck Sharp & Dohme LLC
Investigators
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Study Director: Melinda Willard, PhD Loxo Oncology, Inc.
Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04956640    
Other Study ID Numbers: LOXO-RAS-20001
2021-000595-12 ( EudraCT Number )
J3M-OX-JZQA ( Other Identifier: Eli Lilly and Company )
KEYNOTE E27 ( Other Identifier: Merck )
First Posted: July 9, 2021    Key Record Dates
Last Update Posted: January 12, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
Frontline
1L
First Line
Additional relevant MeSH terms:
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Neoplasms
Colorectal Neoplasms
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Ovarian Neoplasms
Endometrial Neoplasms
Biliary Tract Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases