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

NCT ID: NCT06561685

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-19

Study Completion Date

2027-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Solid Tumor Advanced Solid Tumor Non-small Cell Lung Cancer SMARCA4-Deficient Tumor

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LY4050784 (Phase 1a - Dose Escalation)

Escalating doses of LY4050784 administered orally.

Group Type EXPERIMENTAL

LY4050784

Intervention Type DRUG

Oral

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

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

Group Type EXPERIMENTAL

LY4050784

Intervention Type DRUG

Oral

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

LY4050784 administered orally.

Group Type EXPERIMENTAL

LY4050784

Intervention Type DRUG

Oral

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.

Group Type EXPERIMENTAL

LY4050784

Intervention Type DRUG

Oral

Pembrolizumab

Intervention Type DRUG

Administered IV.

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.

Group Type EXPERIMENTAL

LY4050784

Intervention Type DRUG

Oral

Pembrolizumab

Intervention Type DRUG

Administered IV.

Cisplatin

Intervention Type DRUG

Administered IV.

Carboplatin

Intervention Type DRUG

Administered IV.

Pemetrexed

Intervention Type DRUG

Administered IV.

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.

Group Type EXPERIMENTAL

LY4050784

Intervention Type DRUG

Oral

Pembrolizumab

Intervention Type DRUG

Administered IV.

Carboplatin

Intervention Type DRUG

Administered IV.

Paclitaxel

Intervention Type DRUG

Administered IV.

Nab paclitaxel

Intervention Type DRUG

Administered IV.

Interventions

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LY4050784

Oral

Intervention Type DRUG

Pembrolizumab

Administered IV.

Intervention Type DRUG

Cisplatin

Administered IV.

Intervention Type DRUG

Carboplatin

Administered IV.

Intervention Type DRUG

Pemetrexed

Administered IV.

Intervention Type DRUG

Paclitaxel

Administered IV.

Intervention Type DRUG

Nab paclitaxel

Administered IV.

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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UCLA

Santa Monica, California, United States

Site Status NOT_YET_RECRUITING

University of Colorado Health Hospital

Aurora, Colorado, United States

Site Status NOT_YET_RECRUITING

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, United States

Site Status RECRUITING

Florida Cancer Specialists ORLANDO/DDU

Lake Mary, Florida, United States

Site Status RECRUITING

University of Miami

Miami, Florida, United States

Site Status RECRUITING

University of Chicago

New Lenox, Illinois, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Ohio State University Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

National Cancer Center Hospital

Chūōku, , Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa, , Japan

Site Status RECRUITING

The Cancer Institute Hospital of JFCR

Kōtō City, , Japan

Site Status RECRUITING

Shizuoka Cancer Center

Nagaizumi-cho,Sunto-gun, , Japan

Site Status RECRUITING

Aichi Cancer Center Hospital

Nagoya, , Japan

Site Status RECRUITING

Countries

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United States Japan

Central Contacts

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

Role: CONTACT

Phone: 1-317-615-4559

Email: [email protected]

Physicians interested in becoming principal investigators please contact

Role: CONTACT

Email: [email protected]

Related Links

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https://trials.lilly.com/en-US/trial/528616

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

Other Identifiers

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J5M-OX-JOXA

Identifier Type: OTHER

Identifier Source: secondary_id

27191

Identifier Type: -

Identifier Source: org_study_id