Recruiting
Phase 1

LY4050784

Sponsor:

Eli Lilly and Company

Code:

NCT06561685

Conditions

Metastatic Solid Tumor

Advanced Solid Tumor

Non-small Cell Lung Cancer

SMARCA4-Deficient Tumor

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

LY4050784

Pembrolizumab

Cisplatin

Carboplatin

Pemetrexed

Study Details

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.

Conditions

Metastatic Solid Tumor

Advanced Solid Tumor

Non-small Cell Lung Cancer

SMARCA4-Deficient Tumor

Study ID

NCT06561685

Start date

Sep 19, 2024

Status verified date

Aug, 2026

Completion date

Oct, 2027

Anticipated

Primary completion date

Oct, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

340 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: LY4050784 (Phase 1a - Dose Escalation)

Escalating doses of LY4050784 administered orally.

experimental: LY4050784 (Phase 1b - Dose Optimization/Part A)

Comparing 2 or more doses (evaluated during dose escalation) of LY4050784 administered orally.

experimental: LY4050784 (Phase 1b - Dose Expansion/Part B)

LY4050784 administered orally.

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.

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.

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.

Interventions

LY4050784

Oral

Pembrolizumab

Administered IV.

Cisplatin

Administered IV.

Carboplatin

Administered IV.

Pemetrexed

Administered IV.

Paclitaxel

Administered IV.

Nab paclitaxel

Administered IV.

Primary outcome measure

  • 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 ]
  • 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 ]
  • Phase 1b: To assess the antitumor activity of LY4050784 Monotherapy: Overall response rate (ORR) [ Time Frame: 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 ]
  • 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 ]

Central Contacts and Locations

Central contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

1-317-615-4559LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

UCLA

Recruiting

Santa Monica, California, United States, 90404

University of Colorado Health Hospital

Recruiting

Aurora, Colorado, United States, 80045

Sarah Cannon Research Institute at HealthOne

Recruiting

Denver, Colorado, United States, 80218

University of Miami

Recruiting

Miami, Florida, United States, 33136

University of Chicago

Recruiting

New Lenox, Illinois, United States, 60451

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Ohio State University Hospital

Recruiting

Columbus, Ohio, United States, 43210

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Vanderbilt-Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232-6307

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-4009

USO-Virginia Cancer Specialists, PC

Recruiting

Fairfax, Virginia, United States, 22031

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

More Information

Sponsor

Eli Lilly and Company

Last update posted

Aug 7, 2026

Last verified

Aug, 2026

Keywords

  • SMARCA2
  • SMARCA4
  • Lung cancer
  • BRM
  • BRG1
  • Adenocarcinoma
  • Squamous cell carcinoma
  • Targeted therapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-08-07.