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

April 17, 2026 updated by: Eli Lilly and Company

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
340

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: LillyTrials@Lilly.com

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France, 33 076
        • Not yet recruiting
        • Institut Bergonie
      • Paris, France, 75248
        • Recruiting
        • Institut Curie
      • Villejuif, France, 94800
        • Not yet recruiting
        • Institut Gustave Roussy-Gustave Roussy Cancer Center -Ditep
  • Germany
      • Berlin, Germany, 10117
        • Not yet recruiting
        • Charite-Universitatsmedizin Berlin
      • Essen, Germany, 45147
        • Not yet recruiting
        • Universitaetsklinikum Essen
      • Frankfurt am Main, Germany, 60488
        • Not yet recruiting
        • Krankenhaus Nordwest
  • Japan
      • Chūōku, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
      • Kōtō City, Japan, 135-8550
        • Recruiting
        • The Cancer Institute Hospital of JFCR
      • Nagaizumi-cho,Sunto-gun, Japan, 411-8777
        • Recruiting
        • Shizuoka Cancer Center
      • Nagoya, Japan, 464-8681
        • Recruiting
        • Aichi Cancer Center Hospital
  • South Korea
      • Ilsandong-gu, South Korea, 10408
        • Not yet recruiting
        • National Cancer Center
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital, Yonsei University Health System
      • Suwon, South Korea, 16247
        • Recruiting
        • The Catholic University of Korea, St. Vincent's Hospital
  • Spain
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28040
        • Recruiting
        • South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
  • United States
    • California
      • Santa Monica, California, United States, 90404
        • Recruiting
        • UCLA
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Health Hospital
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Sarah Cannon Research Institute at HealthONE
        • Principal Investigator:
          • Gerald Falchook
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Active, not recruiting
        • Florida Cancer Specialists ORLANDO/DDU
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Principal Investigator:
          • Gilberto de Lima Lopes
    • Illinois
      • New Lenox, Illinois, United States, 60451
        • Recruiting
        • University of Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Ibiayi Dagogo-Jack
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Jia Luo
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Adam Schoenfeld
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Medical Center
        • Principal Investigator:
          • Benjamin Herzberg
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute
      • Nashville, Tennessee, United States, 37232-6307
        • Recruiting
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • SCRI Oncology Partners
        • Principal Investigator:
          • Vivek Subbiah
    • Texas
      • Houston, Texas, United States, 77030-4009
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Timothy Yap
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • USO-Virginia Cancer Specialists, PC
        • Principal Investigator:
          • Alexander Spira
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LY4050784 (Phase 1a - Dose Escalation)
Escalating doses of LY4050784 administered orally.
Drug: LY4050784
Oral
Experimental: LY4050784 (Phase 1b - Dose Optimization/Part A)
Comparing 2 or more doses (evaluated during dose escalation) of LY4050784 administered orally.
Drug: LY4050784
Oral
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part B)
LY4050784 administered orally.
Drug: LY4050784
Oral
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C1
LY4050784 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.
Drug: Pembrolizumab
Administered IV.
Drug: LY4050784
Oral
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2a
LY4050784 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.
Drug: Pembrolizumab
Administered IV.
Drug: Cisplatin
Administered IV.
Drug: Carboplatin
Administered IV.
Drug: Pemetrexed
Administered IV.
Drug: LY4050784
Oral
Experimental: LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2b
LY4050784 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.
Drug: Pembrolizumab
Administered IV.
Drug: Carboplatin
Administered IV.
Drug: LY4050784
Oral
Drug: Paclitaxel
Administered IV.
Drug: Nab paclitaxel
Administered IV.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase Ia: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs), and Adverse Event(s) (AEs)
Time Frame: 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
Up to Approximately 48 Months or 4 Years
Phase 1a: To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of LY4050784
Time Frame: Up to Approximately 48 Months or 4 Years
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)
Time Frame: Up to Approximately 48 Months or 4 Years
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
Time Frame: 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
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
Time Frame: 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
Up to Approximately 48 Months or 4 Years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To characterize the pharmacokinetics (PK) properties of LY4050784: Maximum Concentration (Cmax)
Time Frame: Cycle 1 (Day 8)
PK: Cmax of LY4050784
Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Time to Maximum Concentration (Tmax)
Time Frame: Cycle 1 (Day 8)
PK: Tmax of LY4050784
Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Area under the concentration versus time curve (AUC)
Time Frame: Cycle 1 (Day 8)
PK: AUC of LY4050784
Cycle 1 (Day 8)
Phase Ia: To evaluate the preliminary antitumor activity of LY4050784: Overall response rate (ORR)
Time Frame: Up to Approximately 48 Months or 4 Years
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Duration of response (DOR)
Time Frame: Up to Approximately 48 Months or 4 Years
DOR per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Time to response (TTR)
Time Frame: Up to Approximately 48 Months or 4 Years
TTR per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Disease control rate (DCR)
Time Frame: Up to Approximately 48 Months or 4 Years
DCR per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4050784: Progression free survival (PFS)
Time Frame: Up to Approximately 48 Months or 4 Years
PFS per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the PK properties of LY4050784 in combination cohorts: Maximum Concentration (Cmax) PK: Cmax of LY4050784
Time Frame: Cycle 1 (Day 8)
Cycle 1 (Day 8)
To evaluate the PK properties of LY4050784 in combination cohorts: Time to Maximum Concentration (Tmax) PK: Tmax of LY4050784
Time Frame: Cycle 1 (Day 8)
Cycle 1 (Day 8)
To evaluate the PK properties of LY4050784 in combination cohorts: Area under the concentration versus time curve (AUC)
Time Frame: Cycle 1 (Day 8)
Cycle 1 (Day 8)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Loxo Oncology, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 19, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 16, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 20, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 27191
  • J5M-OX-JOXA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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