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

Lilly

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: Nab paclitaxel; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Pemetrexed; Drug: LY4050784; Drug: Cisplatin; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT06561685

J5M-OX-JOXA (Other Identifier)

27191

Details and patient eligibility

About

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.

Enrollment: 340 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

340 participants in 6 patient groups

LY4050784 (Phase 1a - Dose Escalation)

Experimental group

Description:

Escalating doses of LY4050784 administered orally.

Treatment:

Drug: LY4050784

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

Experimental group

Description:

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

Treatment:

Drug: LY4050784

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

Experimental group

Description:

LY4050784 administered orally.

Treatment:

Drug: LY4050784

LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C1

Experimental group

Description:

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.

Treatment:

Drug: LY4050784

Drug: Pembrolizumab

LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2a

Experimental group

Description:

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.

Treatment:

Drug: Cisplatin

Drug: LY4050784

Drug: Pemetrexed

Drug: Pembrolizumab

Drug: Carboplatin

LY4050784 (Phase 1b - Dose Expansion/Part C) Cohort C2b

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: LY4050784

Drug: Pembrolizumab

Drug: Carboplatin

Drug: Nab paclitaxel