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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.

Adagrasib 600mg BID without regard to food

Mirati Therapeutics

Julie Meade, MD

This study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID versus 400 mg BID) in patients with NSCLC with KRAS G12C mutation.

849-021 is a phase 2 study of adagrasib monotherapy in which patients are randomized between two dosing regimens. The study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID without regard to food versus 400 mg BID with food) in patients with NSCLC with KRAS G12C mutation and who have received prior treatment with a platinum-based regimen and immune checkpoint inhibitor therapy.

Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)

A Randomized Study of Two Dosing Regimens of Adagrasib in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation

ORR evaluation of subjects treated with adagrasib 600 mg BID without regard to food versus 400 mg BID with food having NSCLC with KRAS G12C mutation (Study Population) will be completed per blinded independent central radiology (BICR) review. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of adagrasib until last dose of adagrasib.

Overall survival is defined as time from date of randomization to date of death due to any cause.

Progression-free survival is defined as time from date of randomization to date of first progression per RECIST 1.1 or death from any cause, whichever occurs first.

Duration of response defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either PD (per BICR review) or death due to any cause, whichever occurs first.

Safety characterized by number of participants with AEs, with abnormal laboratory test results and number of patients modifying or discontinuing study treatment due to an AE:

1. Type, incidence, severity, timing, seriousness, and relationship to study treatment of Adverse Events.
2. Laboratory abnormalities as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment.
3. Number of patients modifying or discontinuing study treatment due to Adverse Event.

Sparse concentration data from this study will be pooled with other studies and analyzed using population PK methods to derive individual exposure parameters. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Patient reported outcomes (PROs) will be used to assess symptomatic toxicity of adagrasib using the NCI Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Measurement System. PRO items reflect the specific symptom 1) frequency, severity, interference with usual or daily activities, 2) amount, or 3) presence or absence. PRO-CTCAE responses are scored from 0 (low) to 4 (high), or 0/1 for absent/present, and scores for each attribute (frequency, severity and/or interference) are presented descriptively.

Patient reported quality of life questionnaire will be used to assess five dimensions of patient health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using the 5-Level EQ-5D version (EQ-5D-5L) established by the EuroQol Group. This is presented descriptively, and patient responses correspond to a value of 1 (low) or 5 (high). Additionally, a one- page Visual Analog Scale (VAS) will be provided to patients so they may report their self-rated health from the best (100) and worst (0) health imaginable.

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Pancreatic Cancer

Herbal and Botanical

Cola

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

MRTX849

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 participants with treatment related adverse events

Number of patients with dose limiting toxicity

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

Boehringer Ingelheim

The implantable IBV™ device is a one-way valve, designed for placement in selected regions of the bronchial tree using a flexible bronchoscope.

EndoBronchial Valve

Chrtistophe Dooms, MD, PhD

Because an endobronchial valve is a one-way inspiratory airway blocker, it is hypothesized that it could be also used for controlling persistent air leaks while maintaining the drainage of secretions. The U.S. Food and Drug Administration approved in October 2008 the Spiration valve system designed to control air leaks in the lung that persist after lung surgery. This prospective observational study aims to evaluate the efficacy and safety of Spiration endobronchial valves in a prospective series of consecutive patients with a prolonged persistent air leak after anatomic surgical resection for cancer.

Persistent Air Leak (PAL) is independently associated with prolonged hospital length of stay, decreased patient satisfaction, increased morbidity or postoperative complications, and adds significantly to the cost. The management of air leaks is primarily preventive and therefore starts in the operating room with surgical techniques that can minimize the occurrence of post-operative air leaks, such as the creation of pleural tents or use of suture line glues or sealants. Notwithstanding some patients will after a lung resection have PAL. Any minimal invasive method that helps to increase our ability to treat (reduce and/or stop) the air leak in these latest cases carries an enormous clinical as well as cost-saving potential. Bronchoscopic occlusion of a segmental or subsegmental bronchus using endobronchial valves is such a less invasive method which has shown in case reports to interrupt an air leak.

Endobronchial Valves in Persistent Air Leak

Efficacy of Endobronchial Valves in Persistent Air Leak After Anatomical Pulmonary Resection for Cancer.

Clinical efficacy on air leak cessation allowing drain(s) removal.

* Complications related to endobronchial valve: fever, pulmonary infection, valve migration, pneumothorax requiring treatment.
* Avoidance of ambulatory Heimlich valve and re-operation.
* Timing of drain removal.

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.
Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)	NCT05853575	Advanced Cancer Metastatic Canc... Malignant Neopl...	Adagrasib	18 Years -	Mirati Therapeutics Inc.
Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)	NCT05853575	Advanced Cancer Metastatic Canc... Malignant Neopl...	Adagrasib	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.
Endobronchial Valves in Persistent Air Leak	NCT01451359	Malignant Neopl...	EndoBronchial V...	18 Years -	Universitaire Ziekenhuizen KU Leuven

Spots Global Cancer Trial Database for malignant neoplasm of lung