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

Launched by ELI LILLY AND COMPANY · Aug 16, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called LY4050784 to see if it is safe and effective for people with advanced or metastatic solid tumors, particularly those with a specific genetic change known as a SMARCA4 alteration. The trial is for patients who have already tried standard treatments that didn't work, decided not to pursue them, or have no standard options available. It is divided into two parts: the first part will gradually increase the dose of the drug to find the highest amount that is safe, and the second part will focus on determining the best dose for treating patients. The entire study will take about four years.

To be eligible for this trial, participants need to have certain types of solid tumors with the SMARCA4 alteration, including non-small cell lung cancer or other tumors. They should also have already received some treatments for their cancer or be in a situation where there are no other options. Participants will be monitored throughout the study and can expect regular check-ups to assess their health. It's important to note that individuals who are pregnant, breastfeeding, or have certain medical conditions may not qualify for the trial.

Gender

ALL

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)