A First-in-Human, Phase 1a/1b Trial to Assess the Safety, Tolerability and Preliminary Efficacy of LY4175408, an Antibody Drug Conjugate Targeting Protein Tyrosine Kinase 7-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Eli Lilly and Company
- Enrollment
- 240
- Locations
- 44
- Primary Endpoint
- Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 (≤)
- •For dose optimization/dose and expansion cohorts (Cohort A2, Cohort B/C): Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •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 B
- •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.
Arms & Interventions
Phase 1b Dose Expansion (Cohort B)
LY4175408 administered IV
Intervention: LY4175408 (Drug)
Phase 1a Dose Escalation (Cohort A1)
Escalating doses of LY4175408 administered intravenously (IV)
Intervention: LY4175408 (Drug)
Phase 1a Dose Optimization (Cohort A2)
Two or more doses of LY4175408 (evaluated during dose escalation) administered IV
Intervention: LY4175408 (Drug)
Phase 1b Dose Expansion (Cohort B1)
LY4175408 administered IV followed by pembrolizumab administered IV
Intervention: Pembrolizumab (Drug)
Phase 1b Dose Expansion (Cohort B2)
LY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV
Intervention: Cisplatin (Drug)
Phase 1b Dose Expansion (Cohorts C1, C2 and C3)
LY4175408 administered IV
Intervention: LY4175408 (Drug)
Phase 1b Dose Expansion (Cohort B2)
LY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV
Intervention: Carboplatin (Drug)
Phase 1b Dose Expansion (Cohort B1)
LY4175408 administered IV followed by pembrolizumab administered IV
Intervention: LY4175408 (Drug)
Phase 1b Dose Expansion (Cohort B2)
LY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV
Intervention: Pembrolizumab (Drug)
Phase 1b Dose Expansion (Cohort B2)
LY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV
Intervention: LY4175408 (Drug)
Outcomes
Primary Outcomes
Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408
Time Frame: 1 Cycle (21 days)
Phase 1b-Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)
Time Frame: Baseline up to approximately 4 years
Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408
Time Frame: 1 Cycle (21 days)
Phase 1b-Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)
Time Frame: Baseline up to approximately 4 years
Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Secondary Outcomes
- Phase 1a and 1b-Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of LY4175408 (total antibody, conjugated antibody, free payload)(First 4 cycles (84 days))
- Phase 1a-ORR: Percentage of Participants with Best Response of CR or PR(Baseline up to approximately 4 years)
- Phase 1a and 1b-Time to Response (TTR)(Baseline up to approximately 4 years)
- Phase 1a and 1b-Progression-free Survival (PFS)(Baseline up to approximately 4 years)
- Phase 1a and 1b-PK: Area under the Concentration versus Time Curve (AUC) of LY4175408 (total antibody, conjugated antibody, free payload)(First 4 cycles (84 days))
- Phase 1a and 1b-Disease Control Rate (DCR)(Baseline up to approximately 4 years)
- Phase 1a and 1b-Duration of Response (DOR)(Baseline up to approximately 4 years)
- Phase 1a and 1b-Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of LY4175408 (total antibody, conjugated antibody, free payload)(First 4 cycles (84 days))
- Phase 1a and 1b-PK: Area under the Concentration versus Time Curve (AUC) of LY4175408 (total antibody, conjugated antibody, free payload)(First 4 cycles (84 days))
- Phase 1a-ORR: Percentage of Participants with Best Response of CR or PR(Baseline up to approximately 4 years)
- Phase 1a and 1b-Time to Response (TTR)(Baseline up to approximately 4 years)
- Phase 1a and 1b-Progression-free Survival (PFS)(Baseline up to approximately 4 years)
- Phase 1a and 1b-Disease Control Rate (DCR)(Baseline up to approximately 4 years)