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RecruitingPhase 1

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 4 years

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "The study will last up to approximately 4 years."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether LY4050784 is safe, how well people handle it, and whether it works alone or with other cancer drugs. It is for people with solid tumors that have grown into nearby areas or spread to other parts of the body and have a change in SMARCA4, also called BRG1.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have a solid tumor that has grown nearby or spread, with a change in SMARCA4 (BRG1). The first dose-testing part allows any change in this gene.
  • For Phase 1b, have a gene change that is known or likely to stop SMARCA4 from working, or have no SMARCA4 protein in the tumor.
  • For Phase 1b Parts A and C, have non-small cell lung cancer. If it has only spread nearby, treatment aimed at curing it in that area must not be suitable. Part B is for other tumor types.
  • For Phase 1a and Phase 1b Part B, have received all suitable standard treatments, refuse the remaining best standard treatment, or have no standard treatment available.
  • For Phase 1b Part A, have had at least one course of treatment for cancer that has grown nearby or spread. Part C allows people with or without past treatment.
  • Have cancer that can be measured by study rules for Phase 1b and extra enrollment slots in Phase 1a. Other Phase 1a slots allow cancer that cannot be measured.
  • Be fully active or able to do light work, even if hard physical activity is limited (ECOG score of 0 or 1).

Who can't join

  • Have a change known or likely to stop SMARCA2 (BRM) from working, or a cancer known to be linked to changes in this gene.
  • Have used drugs that block or break down SMARCA2 (BRM). This may be allowed in the first dose-testing part.
  • Have known or suspected cancer affecting the brain or spinal cord that is untreated or not controlled.
  • Have a history of increased risk for a heart rhythm problem called prolonged QT, or a serious abnormal heartbeat.
  • Have serious heart or blood vessel disease.
  • Have another separate cancer that was active or treated within 2 years before joining.
  • Are pregnant, breastfeeding, planning to breastfeed, or expecting to become pregnant or father a child during the study or within 6 months after the last dose.
  • For Part C only: have a history of active disease in which the immune system attacks the body, a stem cell or organ transplant from a donor, or a weakened immune system within the past 2 years.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 sites (17)

CA

CO

FL

IL

MA

NY

OH

TN

TX

VA

WI