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

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Pancrelipase

Pancreatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.

To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients

The RP2D of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel determined in Part A will be used in Part B dose expansion.

avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel

Dalila Stanfield

Andrew Ko, MD

Clinical Trials

Shergill Ardaman, MD

Kimberly Perez

Kimberly Perez, MD

Lynne Mitchell

Kian-Huat Lim, MD

Kristen Spencer

Kristen Spencer, DO

Casey Owens

Despina Siolas, MD

Anna Varghese, MD

Luda Mazaleuskya

Mark O'Hara, MD

Sierra Mitchell

Ignacio Garrido-Laguna

Colleen Soleau

Vincent Picozzi, MD

Rachael Safyan

Rachael Safyan, MD

This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with Pancreatic Ductal Adenocarcinoma (PDAC) who have been previously untreated.

This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients previously untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC).

Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer

A Phase 1b/2a Study of Gemcitabine and Nab-paclitaxel in Combination With Avutometinib (VS-6766) and Defactinib in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas

Confirmed overall response rate (ORR) (partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\])

From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause

Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale

Count of abnormal laboratory values by grade

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Esophageal Neoplasms

Cholangiocarcinoma

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Stomach Neoplasms

Glioblastoma

Head and Neck Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neoplasms, Glandular and Epithelial

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Esophageal Cancer

Ovarian Cancer

Bile Duct Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Small Intestine Cancer

Neuroepithelioma

Ulixertinib (BVD-523) is an oral, first-in-class ERK1/2 inhibitor

Ulixertinib (BVD-523)

xCures Clinical Operations

Louis B Nabors, MD

Marshall Schreeder, MD

Jose Galeas, MD

David Palchak, MD

Richard M Green, MD

Michael Demeure, MD

Naveed Wagle, MD

Benjamin A Weinberg, MD

Jennifer E. Tseng, MD

Joshua Lukenbill, DO

Jon Olson, MD

Philip L. Brooks, MD

Mohammad Mobayed, MD

Nathan B. Green, DO

Seth Cohen, MD

Carl J. Minniti Jr., MD

Bonni Guerin, MD

MInsig Choi, MD

Manish Bhandari, MD

Rex Mowat, MD

Suresh Nair, MD

Elena G Chiorean, MD

The objective of this expanded access program is to provide ulixertinib (BVD-523) for compassionate use in advanced cancer patients with MAPK pathway-altered solid tumor(s), including but not limited to KRAS, NRAS, HRAS, BRAF, MEK, and ERK mutations who have incomplete response to or have exhausted available therapies.

Ulixertinib is available for treatment as monotherapy or in combination with other clinically tolerable agent(s), conditionally approved by the drug manufacturer.

Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies

Cancer Commons

xCures

Recurrence

in patients with a NSCLC KRAS-other (non-G12V) tumor

in patients with a NSCLC BRAF-V600E tumor

in patients with a NSCLC BRAF-non-V600E tumor

avutometinib (VS-6766)

avutometinib (VS-6766) and Defactinib

Ross Camidge, MD, PhD

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with KRAS and BRAF mutant NSCLC following treatment with an appropriate platinum-based regimen and an approved immune checkpoint inhibitor (CPI).

A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer

A Phase 2 Study of Avutometinib (VS-6766) (Dual RAF/MEK Inhibitor) as a Single Agent and In Combination With Defactinib (FAK Inhibitor) in Recurrent KRAS-Mutant (KRAS-MT) and BRAF-Mutant (BRAF-MT) Non-Small Cell Lung Cancer (NSCLC) (RAMP 202)

Adverse events (AEs), serious AEs (SAEs), vital signs, physical examinations, clinical laboratory values, and tolerability (dose interruptions/reductions)

Proportioned subjects achieving a CR or PR as assess by the investigator

Time of first response to PD as assessed by the IRC

CR and PR stable disease as assessed by the IRC

Sotorasib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

To determine the recommended phase 2 dose (RP2D) for avutometinib (VS 6766) in combination with sotorasib in KRAS G12C inhibitor naïve and exposed patients

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

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

To determine the recommended phase 2 dose (RP2D) for avutometinib (VS-6766) in combination with sotorasib and defactinib in KRAS G12C inhibitor exposed patients

The RP2D of avutometinib + sotorasib determined in Part A will be used in Part B dose expansion

avutometinib and sotorasib

The RP2D of avutometinib + sotorasib + defactinib determined in Part A will be used in Part B dose expansion

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.
Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer	NCT05669482	KRAS Activating... Metastatic Canc... Pancreas Cancer Neoplasms Pancr... Malignant Neopl...	avutometinib (V...	18 Years -	Verastem, Inc.
Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies	NCT04566393	Pancreatic Canc... Small Bowel Can... Colorectal Canc... Melanoma Non Small Cell ... Thyroid Cancer Bladder Cancer Head and Neck C... Gastric Cancer Esophageal Canc... Cholangiocarcin... Ovarian Cancer Hepatocellular ... Glioblastoma MAPK Gene Mutat... KRAS Activating... BRAF Gene Mutat... NRAS Gene Mutat... HRAS Gene Mutat... MEK Mutation ERK Mutation	Ulixertinib (BV...	12 Years -	xCures
A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer	NCT04620330	Non Small Cell ... KRAS Activating...	avutometinib (V... avutometinib (V...	18 Years -	Verastem, Inc.
Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients	NCT05074810	Non Small Cell ... KRAS Activating...	avutometinib an... avutometinib an...	18 Years -	Verastem, Inc.
A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer	NCT04620330	Non Small Cell ... KRAS Activating...	avutometinib (V... avutometinib (V...	18 Years -	Verastem, Inc.

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