A Study of LY4175408 in Participants With Advanced Cancer

Lilly

Status and phase: Enrolling; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Triple Negative Breast Cancer; Small Cell Lung Carcinoma; Endometrial Neoplasms

Treatments: Drug: LY4175408; Drug: Cisplatin; Drug: Pembrolizumab; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT07046923

2025-521916-20-00 (EU Trial (CTIS) Number)

J6D-MC-JSDA (Other Identifier)

27401

Details and patient eligibility

About

The purpose of this study is to measure the safety and efficacy of LY4175408 in participants with selected advanced cancer. In addition, this study will evaluate how much LY4175408 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. Participation could last up to 4 years.

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have one of the following advanced or metastatic solid tumor cancers:

  • Non-small cell lung cancer (NSCLC)
  • Small cell lung cancer (SCLC)
  • Endometrial cancer
  • Triple negative breast cancer (TNBC) (characterized by HR-negative disease and HER2-negative expression according to American Society of Clinical Oncology (ASCO) - College of American Pathologists guidelines).

• Received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating investigator (except in Cohort B1 and B2 expansion, which require participants who are treatment naive in the advanced metastatic setting); OR the individual is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease.

• Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to (≤) 1.

• For dose optimization/dose and expansion cohorts (Cohort A2, Cohort B/C): Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

• Cohorts B1/B2: NSCLC with no known actionable genomic alterations. ≤2 prior lines of systemic therapy for advanced or metastatic disease in safety lead-in; no prior systemic therapy in expansion

Exclusion criteria

• Prior treatment with a protein tyrosine kinase 7 (PTK7) antibody-drug conjugate (ADC) with a topoisomerase I inhibitor as payload (prior therapy with a PTK7 ADC with a non-topoisomerase I inhibitor payload OR non-PTK7 ADC with any payload is permitted). Prior topoisomerase I-based ADCs are not allowed in cohorts A2, B1 or B2.
• Any serious unresolved toxicities from prior therapy.
• Individual with known or suspected history of uncontrolled central nervous system (CNS) metastases.
• Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection.
• Significant cardiovascular disease.
• Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 milliseconds (ms)
• History of pneumonitis/interstitial lung disease.
• Individuals who are pregnant, breastfeeding, or plan to breastfeed during the trial or within 30 days of the last dose of trial intervention.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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240 participants in 5 patient groups

Phase 1a Dose Escalation (Cohort A1)

Experimental group

Description:

Escalating doses of LY4175408 administered intravenously (IV)

Treatment:

Drug: LY4175408

Phase 1a Dose Optimization (Cohort A2)

Experimental group

Description:

Two or more doses of LY4175408 (evaluated during dose escalation) administered IV

Treatment:

Drug: LY4175408

Phase 1b Dose Expansion (Cohort B1)

Experimental group

Description:

LY4175408 administered IV followed by pembrolizumab administered IV

Treatment:

Drug: Pembrolizumab

Drug: LY4175408

Phase 1b Dose Expansion (Cohort B2)

Experimental group

Description:

LY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV

Treatment:

Drug: Carboplatin

Drug: Pembrolizumab

Drug: Cisplatin

Drug: LY4175408

Phase 1b Dose Expansion (Cohorts C1, C2 and C3)

Experimental group

Description:

LY4175408 administered IV

Treatment:

Drug: LY4175408