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

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: Recruiting
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Non-small Cell Lung Cancer; SMARCA4-Deficient Tumor
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Drug: LY4050784; Drug: Paclitaxel; Drug: Nab paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 1

Contacts and Locations

• Study Contact: 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: Name: Physicians interested in becoming principal investigators please contact; Email: clinical_inquiry_hub@lilly.com

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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the pharmacokinetics (PK) properties of LY4050784: Maximum Concentration (Cmax)	PK: Cmax of LY4050784	Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Time to Maximum Concentration (Tmax)	PK: Tmax of LY4050784	Cycle 1 (Day 8)
To characterize the PK properties of LY4050784: Area under the concentration versus time curve (AUC)	PK: AUC of LY4050784	Cycle 1 (Day 8)
Phase Ia: To evaluate the preliminary antitumor activity of LY4050784: 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
To evaluate the preliminary antitumor activity of LY4050784: Duration of response (DOR)	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)	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)	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)	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		Cycle 1 (Day 8)
To evaluate the PK properties of LY4050784 in combination cohorts: Time to Maximum Concentration (Tmax) PK: Tmax of LY4050784		Cycle 1 (Day 8)
To evaluate the PK properties of LY4050784 in combination cohorts: Area under the concentration versus time curve (AUC)		Cycle 1 (Day 8)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: 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

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: August 16, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Adenocarcinoma; Lung cancer; Targeted therapy; BRG1; BRM; SMARCA4; Squamous cell carcinoma; SMARCA2
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Lung Neoplasms; Carcinoma, Squamous Cell; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Health Care Economics and Organizations; Platinum Compounds; Economics; Pemetrexed; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; Taxes
• Other Study ID 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