RECRUITING

A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors

Conditions

Metastatic Solid Tumor Advanced Solid Tumor Non-small Cell Lung Cancer SMARCA4-Deficient Tumor SMARCA2 SMARCA4 Lung cancer BRM BRG1 Adenocarcinoma Squamous cell carcinoma Targeted therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The main purpose of this study is to find out whether the study drug, LY4050784, is safe, tolerable and effective in participants alone or in combination with other anticancer agents. In addition, with locally advanced or metastatic solid tumors with a BRG1 (Brahma-related gene 1, also known as SMARCA4) alteration who have previously received, do not qualify for, or are refusing standard of care treatments, or there is no standard therapy available for the disease. The study is conducted in two parts - phase Ia (dose-escalation) and phase Ib (dose-optimization, dose-expansion). The study will last up to approximately 4 years.

Official Title

An Open-label, Multicenter Study of LY4050784, a Selective SMARCA2/BRM Inhibitor, in Advanced Solid Tumor Malignancies With SMARCA4/BRG1 Alterations

Quick Facts

Study Start:2024-12-13

Study Completion:2028-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06561685

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Have one of the following locally advanced or metastatic solid tumor malignancy with SMARCA4 (BRG1) alteration: * Phase 1a dose escalation: Presence of any alteration in SMARCA4 (BRG1) * Phase 1b expansion: Part A: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression. * Phase 1b expansion: Part B: Any tumor type (other than NSCLC) that has the presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression. * Phase 1b expansion: Part C: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression. * Prior Systemic Therapy Criteria: * Phase 1a dose escalation and Phase 1b (Part B): Participants who received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating Investigator; or the individual is refusing the remaining most appropriate standard of care treatment; or there is no standard therapy available for the disease. * Phase 1b expansion (Part A): Participants must have received at least one line of therapy for advanced or metastatic disease. * Phase 1b expansion (Part C): Participants may be treatment naïve or have received therapy for advanced or metastatic disease * Measurability of disease * Phase 1a dose escalation (excluding backfill): measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) * Phase 1a backfill and Phase 1b expansion: Measurable disease required as defined by RECIST v1.1 * Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1	* Participants with known or likely loss of function alteration of SMARCA2 (BRM) or malignancy with known association with SMARCA2 (BRM) alterations * Prior exposure to SMARCA2 (BRM) inhibitor(s) and/or degrader(s) (prior exposure may be permitted for dose escalation) * Participants with known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement * Participants with history of increased risk of prolonged QT or significant arrythmia * Significant cardiovascular disease * Participants with active and/or treated for an additional primary malignancy within 2 years prior to enrolment * Participants who are pregnant, breastfeeding or plan to breastfeed or expecting to conceive or father children during study or within 6 months after the last dose of study intervention * Participants with history of active autoimmune diseases, history of allogenic stem cell/organ transplant or compromised immune system within past 2 years (Part C only)

Inclusion Criteria

Exclusion Criteria

* Have one of the following locally advanced or metastatic solid tumor malignancy with SMARCA4 (BRG1) alteration:
* Phase 1a dose escalation: Presence of any alteration in SMARCA4 (BRG1)
* Phase 1b expansion: Part A: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
* Phase 1b expansion: Part B: Any tumor type (other than NSCLC) that has the presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
* Phase 1b expansion: Part C: Non-small Cell Lung Cancer (NSCLC) that is locally advanced and not suitable for definitive locoregional therapy, or metastatic with presence of a known or likely loss of function alteration in SMARCA4 (BRG1) or loss of protein expression.
* Prior Systemic Therapy Criteria:
* Phase 1a dose escalation and Phase 1b (Part B): Participants who received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating Investigator; or the individual is refusing the remaining most appropriate standard of care treatment; or there is no standard therapy available for the disease.
* Phase 1b expansion (Part A): Participants must have received at least one line of therapy for advanced or metastatic disease.
* Phase 1b expansion (Part C): Participants may be treatment naïve or have received therapy for advanced or metastatic disease
* Measurability of disease
* Phase 1a dose escalation (excluding backfill): measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
* Phase 1a backfill and Phase 1b expansion: Measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

* Participants with known or likely loss of function alteration of SMARCA2 (BRM) or malignancy with known association with SMARCA2 (BRM) alterations
* Prior exposure to SMARCA2 (BRM) inhibitor(s) and/or degrader(s) (prior exposure may be permitted for dose escalation)
* Participants with known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement
* Participants with history of increased risk of prolonged QT or significant arrythmia
* Significant cardiovascular disease
* Participants with active and/or treated for an additional primary malignancy within 2 years prior to enrolment
* Participants who are pregnant, breastfeeding or plan to breastfeed or expecting to conceive or father children during study or within 6 months after the last dose of study intervention
* Participants with history of active autoimmune diseases, history of allogenic stem cell/organ transplant or compromised immune system within past 2 years (Part C only)

Contacts and Locations

Study Contact

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

CONTACT

13176154559

clinical_inquiry_hub@lilly.com

Principal Investigator

Call 1-877-CTLILLY (1-877-285-Call 1-87) or 1-317-615-4559 Cal Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

STUDY_DIRECTOR

Eli Lilly and Company

Study Locations (Sites)

UCLA

Santa Monica, California, 90404

United States

University of Colorado Health Hospital

Aurora, Colorado, 80045

United States

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218

United States

Florida Cancer Specialists ORLANDO/DDU

Lake Mary, Florida, 32746

United States

University of Miami

Miami, Florida, 33136

United States

The University of Illinois at Chicago

Chicago, Illinois, 60637

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Columbia University Medical Center

New York, New York, 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Ohio State University Hospital

Columbus, Ohio, 43210

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

SCRI Oncology Partners

Nashville, Tennessee, 37203

United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6307

United States

MD Anderson Cancer Center

Houston, Texas, 77030-4009

United States

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Eli Lilly and Company

Call 1-877-CTLILLY (1-877-285-Call 1-87) or 1-317-615-4559 Cal Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), STUDY_DIRECTOR, Eli Lilly and Company

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-13

Study Completion Date2028-05

Study Record Updates

Study Start Date2024-12-13

Study Completion Date2028-05

Terms related to this study

Keywords Provided by Researchers

SMARCA2
SMARCA4
Lung cancer
BRM
BRG1
Adenocarcinoma
Squamous cell carcinoma
Targeted therapy

Additional Relevant MeSH Terms

Metastatic Solid Tumor
Advanced Solid Tumor
Non-small Cell Lung Cancer
SMARCA4-Deficient Tumor