A Study of LY4050784 in Participants With Advanced or Metastatic Solid Tumors
An Open-label, Multicenter Study of LY4050784, a Selective SMARCA2/BRM Inhibitor, in Advanced Solid Tumor Malignancies With SMARCA4/BRG1 Alterations
2 other identifiers
interventional
340
6 countries
33
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2024
Typical duration for phase_1
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 16, 2024
CompletedFirst Posted
Study publicly available on registry
August 20, 2024
CompletedStudy Start
First participant enrolled
September 19, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2027
April 20, 2026
April 1, 2026
3 years
August 16, 2024
April 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Phase Ia: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs), and Adverse Event(s) (AEs)
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Up to Approximately 48 Months or 4 Years
Phase 1a: To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of LY4050784
Number of participants with dose-limiting toxicities (DLTs)
Up to Approximately 48 Months or 4 Years
Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR)
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Up to Approximately 48 Months or 4 Years
Phase 1b (Dose optimization only): To confirm the RP2D/optimal dose based on safety and efficacy of LY4050784
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
Up to Approximately 48 Months or 4 Years
Phase 1b (Combination cohorts/Part C): To assess the safety and tolerability of LY4050784 when administered in combination with other anticancer agents
A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module
Up to Approximately 48 Months or 4 Years
Secondary Outcomes (11)
To characterize the pharmacokinetics (PK) properties of LY4050784: Maximum Concentration (Cmax)
Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Time to Maximum Concentration (Tmax)
Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Area under the concentration versus time curve (AUC)
Cycle 1 (Day 8)
Phase Ia: To evaluate the preliminary antitumor activity of LY4050784: Overall response rate (ORR)
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Duration of response (DOR)
Up to Approximately 48 Months or 4 Years
- +6 more secondary outcomes
Study Arms (6)
LY4050784 (Phase 1a - Dose Escalation)
EXPERIMENTALEscalating doses of LY4050784 administered orally.
LY4050784 (Phase 1b - Dose Optimization/Part A)
EXPERIMENTALComparing 2 or more doses (evaluated during dose escalation) of LY4050784 administered orally.
LY4050784 (Phase 1b - Dose Expansion/Part B)
EXPERIMENTALLY4050784 administered orally.
LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C1
EXPERIMENTALLY4050784 administered orally in combination in combination with pembrolizumab administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2a
EXPERIMENTALLY4050784 administered orally in combination in combination with pembrolizumab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2b
EXPERIMENTALLY4050784 administered orally in combination in combination with pembrolizumab, paclitaxel/nab-paclitaxel and carboplatin administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
Interventions
Administered IV.
Oral
Administered IV.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (33)
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
University of Chicago
New Lenox, Illinois, 60451, 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
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, 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
Institut Bergonie
Bordeaux, 33 076, France
Institut Curie
Paris, 75248, France
Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP
Villejuif, 94800, France
Charite-Universitatsmedizin Berlin
Berlin, 10117, Germany
Universitaetsklinikum Essen
Essen, 45147, Germany
Krankenhaus Nordwest
Frankfurt am Main, 60488, Germany
National Cancer Center Hospital
Chūōku, 104-0045, Japan
National Cancer Center Hospital East
Kashiwa, 277-8577, Japan
The Cancer Institute Hospital of JFCR
Kōtō City, 135-8550, Japan
Shizuoka Cancer Center
Nagaizumi-cho,Sunto-gun, 411-8777, Japan
Aichi Cancer Center Hospital
Nagoya, 464-8681, Japan
National Cancer Center
Ilsandong-gu, 10408, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
The Catholic University of Korea, St. Vincent's Hospital
Suwon, 16247, South Korea
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
Madrid, 28040, Spain
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Call 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)
Eli Lilly and Company
Central Study Contacts
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACT
Physicians interested in becoming principal investigators please contact
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 16, 2024
First Posted
August 20, 2024
Study Start
September 19, 2024
Primary Completion (Estimated)
October 1, 2027
Study Completion (Estimated)
October 1, 2027
Last Updated
April 20, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share