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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04956640
• Other study ID #: LOXO-RAS-20001
• Secondary ID: 2021-000595-12J3
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 19, 2021
• Est. completion date: February 2026

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: Patient Advocacy
• Phone: 855-569-6305
• Email: clinicaltrials[@]loxooncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• LY3537982
Oral
• Pembrolizumab
Intravenous
• Cetuximab
Intravenous
• Pemetrexed
Intravenous
• Cisplatin
Intravenous
• Carboplatin
Intravenous

Locations

Country	Name	City	State
Australia	Cancer Research SA	Adelaide	South Australia
Australia	Peninsula and Southeast Oncology	Frankston	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	St Vincent's Hospital Sydney	Sydney	New South Wales
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Hospital (Ontario)	Toronto	Ontario
France	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux	Aquitaine
France	Centre Leon Berard	Lyon	Rhône-Alpes
France	Institut du Cancer de Montpellier - Val d'aurelle	Montpellier Cedex 5
France	Institut Curie	Paris CEDEX 05
France	Institut Claudius Regaud - IUCT Oncopole	Toulouse cedex
France	Gustave Roussy	Villejuif Cedex
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Kanazawa University Hospital	Kanazawa-shi	Ishikawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Wakayama Medical University Hospital	Wakayama
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeonranamdo
Korea, Republic of	Asan Medical Center	Seoul	Korea
Korea, Republic of	Seoul National University Hospital	Seoul	Korea
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Novant Health Cancer Institute - Elizabeth	Charlotte	North Carolina
United States	Inova Health System IRB	Fairfax	Virginia
United States	USO-Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Community Health Network	Indianapolis	Indiana
United States	Indiana Univ Melvin & Bren Simon Cancer Center	Indianapolis	Indiana
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	USC Norris Cancer Hospital	Los Angeles	California
United States	University of Wisconsin-Madison Hospital and Health Clinic	Madison	Wisconsin
United States	NYU Langone Health- Long Island	Mineola	New York
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Vanderbilt Univeristy School of Medicine	Nashville	Tennessee
United States	Yale-New Haven Hospital	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone	New York	New York
United States	Chao Family Comprehensive Cancer Ctr.	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas
United States	Florida Cancer Specialists	Sarasota	Florida
United States	START Mountain Region	West Valley City	Utah
United States	Novant Health Cancer Institute - Forsyth	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc., Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy	Measured by the number of patients with dose-limiting toxicities (DLTs)	Cycle 1 (21 Days)
Primary	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)	Cycle 1 (21 Days)
Primary	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	Estimated up to 2 years
Primary	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		Estimated up to 2 years
Primary	To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation		Estimated up to 2 years
Secondary	To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)	ORR	Estimated up to 2 years
Secondary	To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR)	DOR	Estimated up to 2 years
Secondary	To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR)	BOR	Estimated up to 2 years
Secondary	To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR)	TTR	Estimated up to 2 years
Secondary	To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)	DCR	Estimated up to 2 years
Secondary	To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS)	PFS	Estimated up to 2 years
Secondary	To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS)	OS	Estimated up to 2 years
Secondary	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	Estimated up to 2 years
Secondary	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	Estimated up to 2 years
Secondary	To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)	PK: AUC of LY3537982	Predose estimated up to 2 years
Secondary	To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)	PK: Cmax of LY3537982	Predose estimated up to 2 years

External Links

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