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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion 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
Exclusion Criteria:
* 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)
Primary outcome measure(s)
Phase Ia: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs), and Adverse Event(s) (AEs) — Up to Approximately 48 Months or 4 Years A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Phase 1a: To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of LY4050784 — Up to Approximately 48 Months or 4 Years Number of participants with dose-limiting toxicities (DLTs)
Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR) — Up to Approximately 48 Months or 4 Years ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Phase 1b (Dose optimization only): To confirm the RP2D/optimal dose based on safety and efficacy of LY4050784 — Up to Approximately 48 Months or 4 Years A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module, ORR and Duration of Response (DOR) per Investigator
Phase 1b (Combination cohorts/Part C): To assess the safety and tolerability of LY4050784 when administered in combination with other anticancer agents — Up to Approximately 48 Months or 4 Years A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Trial sites (33)
Facility
City
Region
Status
UCLA
Santa Monica
California
Recruiting
University of Colorado Health Hospital
Aurora
Colorado
Recruiting
Sarah Cannon Research Institute at HealthOne
Denver
Colorado
Recruiting
Florida Cancer Specialists ORLANDO/DDU
Lake Mary
Florida
Active Not Recruiting
University of Miami
Miami
Florida
Recruiting
University of Chicago
New Lenox
Illinois
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana-Farber Cancer Institute
Boston
Massachusetts
Recruiting
Columbia University Medical Center
New York
New York
Recruiting
Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
Ohio State University Hospital
Columbus
Ohio
Recruiting
Sarah Cannon Research Institute
Nashville
Tennessee
Recruiting
SCRI Oncology Partners
Nashville
Tennessee
Recruiting
Vanderbilt-Ingram Cancer Center
Nashville
Tennessee
Recruiting
MD Anderson Cancer Center
Houston
Texas
Recruiting
USO-Virginia Cancer Specialists, PC
Fairfax
Virginia
Recruiting
Medical College of Wisconsin
Milwaukee
Wisconsin
Recruiting
Institut Bergonie
Bordeaux
France
Not Yet Recruiting
Institut Curie
Paris
France
Recruiting
Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP
Villejuif
France
Recruiting
Charite-Universitatsmedizin Berlin
Berlin
Germany
Recruiting
Universitaetsklinikum Essen
Essen
Germany
Recruiting
Krankenhaus Nordwest
Frankfurt am Main
Germany
Not Yet Recruiting
National Cancer Center Hospital
Chūōku
Japan
Recruiting
National Cancer Center Hospital East
Kashiwa
Japan
Recruiting
The Cancer Institute Hospital of JFCR
Kōtō City
Japan
Recruiting
Shizuoka Cancer Center
Nagaizumi-cho,Sunto-gun
Japan
Recruiting
Aichi Cancer Center Hospital
Nagoya
Japan
Recruiting
National Cancer Center
Ilsandong-gu
South Korea
Recruiting
Severance Hospital, Yonsei University Health System
Seoul
South Korea
Recruiting
The Catholic University of Korea, St. Vincent's Hospital
Suwon
South Korea
Recruiting
Hospital Universitari Vall d'Hebron
Barcelona
Spain
Not Yet Recruiting
South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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