Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Adagrasib

To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients

To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients

The RP2D of VS-6766 + adagrasib determined in Part A will be used in Part B dose expansion

avutometinib (VS-6766) and adagrasib

Verastem Call Center

Bianca Bacaltos

Collin Blakely, MD

Halle Kuykendall

David Camidge, MD

Yanyan Lou

YanYan Lou, MD

Kaushal Parikh

Kaushal Parikh, MD

Kathryn Arbour, MD

Bryana Roberts

Jared Weiss, MD

MaryAnn Poole

Alexander Spira, MD

Nicholas Pucek

Hui-Zi Chen, MD

MD Verastem

This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) who have been exposed to prior G12C inhibitor and experienced progressive disease.

This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with KRAS G12C mutant NSCLC who have been exposed to prior G12C inhibitor and experienced progressive disease.

Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients

A Phase 1/2 Study of Avutometinib (VS-6766) in Combination With Adagrasib in Patients With KRAS G12C Mutant Non-Small Cell Lung Cancer (NSCLC) (RAMP 204)

Assessment of Dose-limiting toxicities (DLTs)

Confirmed overall response rate per RECIST 1.1

* Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs) assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)
* Severity of Adverse events (AEs) and Serious Adverse Events (SAEs) by toxicity grade assessed by the toxicity grading of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 5.0)
* Duration of Adverse events (AEs) and Serious Adverse Events (SAEs)
* Incidence of clinically significant changes in lab parameters
* Incidence of abnormal vital signs (including systolic and diastolic blood pressure in mmHg)

Corrected ECG QT interval by Fredericia (QTcF)

Time of first response to PD as assessed per RECIST 1.1

CR and PR stable disease as assessed per RECIST 1.1

From the time of first dose of study intervention to PD or death from any cause

From time of first dose of study intervention to death

Area under plasma Concentration (AUC) 0 to t

defined as Complete Response+Partial Response +Stable Disease

Mirati Therapeutics Inc.

Verastem, Inc.

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Pancreatic Cancer

Herbal and Botanical

Amino Acids

Pembrolizumab

Cetuximab

Afatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Cola

Tyrosine

Dose escalation of MRTX849 to determine maximum tolerated dose

Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens

Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC

Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC

Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)

MRTX849 will be administered orally once or twice daily in a continuous regimen

MRTX849

Pembrolizumab is administered as an intravenous infusion once every 3 weeks

Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks

Afatinib will be administered orally once a day in a continuous regimen

Mirati Therapeutics Study Locator Services

Hirak Der-Torossian

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.

This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.

Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1

A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1

Number of participants with treatment related adverse events

Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Number of participants with dose limiting toxicity

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Dose escalation of MRTX849 and BI 1701963 to determine maximum tolerated dose in combination

Expansion cohorts in NSCLC and CRC patients to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with BI 1701963

BI 1701963

This study will evaluate safety, tolerability, drug levels, molecular effects and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors that have a KRAS G12C mutation.

This study will evaluate safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and BI 1701963 is a SOS1 pan-KRAS inhibitor.

Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)

A Phase 1/1b Trial of MRTX849 in Combination With BI 1701963 in Patients With Advanced Solid Tumors With KRAS G12C Mutation

Number of patients with dose limiting toxicity

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients	NCT05375994	Non Small Cell ... KRAS Activating... Advanced Cancer Metastatic Canc... Malignant Neopl... Malignant Neopl...	avutometinib (V...	18 Years -	Verastem, Inc.
Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1	NCT03785249	Advanced Cancer Metastatic Canc... Malignant Neopl...	MRTX849 Pembrolizumab Cetuximab Afatinib	18 Years -	Mirati Therapeutics Inc.
Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)	NCT04975256	Advanced Cancer Metastatic Canc... Malignant Neopl... Malignant Neopl... Malignant Neopl...	MRTX849 BI 1701963	18 Years -	Mirati Therapeutics Inc.
Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1	NCT03785249	Advanced Cancer Metastatic Canc... Malignant Neopl...	MRTX849 Pembrolizumab Cetuximab Afatinib	18 Years -	Mirati Therapeutics Inc.

Spots Global Cancer Trial Database for malignant neoplastic disease