RecruitingRecruiting
A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors
NCT06561685 · Eli Lilly and Company
In plain English
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Official title
An Open-label, Multicenter Study of LY4050784, a Selective SMARCA2/BRM Inhibitor, in Advanced Solid Tumor Malignancies With SMARCA4/BRG1 Alterations
About this study
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 criteria
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)
Study design
Enrollment target: 340 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-09-19
Estimated completion: 2027-10
Last updated: 2026-04-20
Interventions
Drug: LY4050784Drug: PembrolizumabDrug: CisplatinDrug: CarboplatinDrug: PemetrexedDrug: PaclitaxelDrug: Nab paclitaxel
Primary outcomes
- • 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)
- • Phase 1a: To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of LY4050784 (Up to Approximately 48 Months or 4 Years)
- • Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR) (Up to Approximately 48 Months or 4 Years)
Sponsor
Eli Lilly and Company · industry
Contacts & investigators
ContactTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or · contact · LillyTrials@Lilly.com · 1-317-615-4559
ContactPhysicians interested in becoming principal investigators please contact · contact · clinical_inquiry_hub@lilly.com
InvestigatorCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST) · study_director, Eli Lilly and Company
All locations (33)
UCLARecruiting
Santa Monica, California, United States
University of Colorado Health HospitalRecruiting
Aurora, Colorado, United States
Sarah Cannon Research Institute at HealthOneRecruiting
Denver, Colorado, United States
Florida Cancer Specialists ORLANDO/DDUActive Not Recruiting
Lake Mary, Florida, United States
University of MiamiRecruiting
Miami, Florida, United States
University of ChicagoRecruiting
New Lenox, Illinois, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Columbia University Medical CenterRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Ohio State University HospitalRecruiting
Columbus, Ohio, United States
Sarah Cannon Research InstituteRecruiting
Nashville, Tennessee, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer CenterRecruiting
Nashville, Tennessee, United States
MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
USO-Virginia Cancer Specialists, PCRecruiting
Fairfax, Virginia, United States
Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Institut BergonieNot Yet Recruiting
Bordeaux, France
Institut CurieRecruiting
Paris, France
Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEPNot Yet Recruiting
Villejuif, France
Charite-Universitatsmedizin BerlinNot Yet Recruiting
Berlin, Germany
Universitaetsklinikum EssenNot Yet Recruiting
Essen, Germany
Krankenhaus NordwestNot Yet Recruiting
Frankfurt am Main, Germany
National Cancer Center HospitalRecruiting
Chūōku, Japan
National Cancer Center Hospital EastRecruiting
Kashiwa, Japan
The Cancer Institute Hospital of JFCRRecruiting
Kōtō City, Japan
Shizuoka Cancer CenterRecruiting
Nagaizumi-cho,Sunto-gun, Japan
Aichi Cancer Center HospitalRecruiting
Nagoya, Japan
National Cancer CenterNot Yet Recruiting
Ilsandong-gu, South Korea
Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, South Korea
The Catholic University of Korea, St. Vincent's HospitalRecruiting
Suwon, South Korea
Hospital Universitari Vall d'HebronNot Yet Recruiting
Barcelona, Spain
South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez DiazRecruiting
Madrid, Spain