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

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ClinicalTrials.gov Identifier: NCT04956640

Recruitment Status : Recruiting

First Posted : July 9, 2021

Last Update Posted : May 3, 2024

See Contacts and Locations

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

Loxo Oncology, Inc.

Merck Sharp & Dohme LLC

Information provided by (Responsible Party):

Eli Lilly and Company

Tracking Information

First Submitted Date ^ICMJE

July 2, 2021

First Posted Date ^ICMJE

July 9, 2021

Last Update Posted Date

May 3, 2024

Actual Study Start Date ^ICMJE

July 19, 2021

Estimated Primary Completion Date

September 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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)
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)
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
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 ]
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 ]

Original Primary Outcome Measures ^ICMJE

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)
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)

Change History

Current Secondary Outcome Measures ^ICMJE

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

Original Secondary Outcome Measures ^ICMJE

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

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors

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.

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.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Endometrial Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Biliary Tract Neoplasms

Intervention ^ICMJE

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

Study Arms ^ICMJE

Experimental: LY3537982 (Dose Escalation)
LY3537982 administered orally.

Intervention: Drug: LY3537982
Experimental: LY3537982 (Dose Expansion)
LY3537982 administered orally either alone or with another investigational agent.
Interventions:
- Drug: LY3537982
- Drug: Pembrolizumab
- Drug: Cetuximab
- Drug: Pemetrexed
- Drug: Cisplatin
- Drug: Carboplatin

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

450

Original Estimated Enrollment ^ICMJE

260

Estimated Study Completion Date ^ICMJE

September 2025

Estimated Primary Completion Date

September 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Patient Advocacy

855-569-6305

clinicaltrials@loxooncology.com

Listed Location Countries ^ICMJE

Australia, Canada, France, Japan, Korea, Republic of, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04956640

Other Study ID Numbers ^ICMJE

LOXO-RAS-20001
2021-000595-12 ( EudraCT Number )
J3M-OX-JZQA ( Other Identifier: Eli Lilly and Company )
KEYNOTE E27 ( Other Identifier: Merck )

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:

Current Responsible Party

Eli Lilly and Company

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Eli Lilly and Company

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Loxo Oncology, Inc.
Merck Sharp & Dohme LLC

Investigators ^ICMJE

Study Director:

Melinda Willard, PhD

Loxo Oncology, Inc.

PRS Account

Eli Lilly and Company

Verification Date

May 2024

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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