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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
540
Oral
Intravenous
Intravenous
Intravenous
Intravenous
Intravenous
University of Alabama at Birmingham
Birmingham, Alabama, United States
USC Norris Cancer Hospital
Los Angeles, California, United States
Chao Family Comprehensive Cancer Ctr.
Orange, California, United States
Yale-New Haven Hospital
New Haven, Connecticut, United States
AdventHealth Orlando
Orlando, Florida, United States
Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy
Measured by the number of patients with dose-limiting toxicities (DLTs)
Time frame: Cycle 1 (21 Days)
Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents
Measured by the number of patients with dose-limiting toxicities (DLTs)
Time frame: 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 pembrolizumab
Measured by TEAEs
Time frame: Estimated 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 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
To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)
ORR
Time frame: Estimated 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)
DOR
Time frame: Estimated 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)
BOR
Time frame: Estimated 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)
TTR
Time frame: Estimated 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)
DCR
Time frame: Estimated 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)
PFS
Time frame: Estimated 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)
OS
Time frame: Estimated 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 DOR
Time frame: Estimated 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 ORR
Time frame: Estimated up to 2 years
To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)
PK: AUC of LY3537982
Time frame: Predose estimated up to 2 years
To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)
PK: Cmax of LY3537982
Time frame: Predose estimated up to 2 years
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Florida Cancer Specialists
Sarasota, Florida, United States
Indiana Univ Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States
Community Health Network
Indianapolis, Indiana, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
...and 39 more locations