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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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 (≤) 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.
Primary outcome measure(s)
Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408 — 1 Cycle (21 days)
Phase 1b-Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR) — Baseline up to approximately 4 years Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Trial sites (27)
Facility
City
Region
Status
Stanford Medicine Cancer Center
Stanford
California
Recruiting
Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute
Orlando
Florida
Recruiting
Florida Cancer Specialists - Sarasota
Sarasota
Florida
Recruiting
The University of Chicago Medical Center (UCMC)
Chicago
Illinois
Recruiting
Community Health Network
Indianapolis
Indiana
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Washington University
St Louis
Missouri
Recruiting
John Theurer Cancer Center At Hackensack UMC
Hackensack
New Jersey
Recruiting
Columbia University
New York
New York
Recruiting
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
The Ohio State University (OSU) Wexner Medical Center
Columbus
Ohio
Recruiting
Sarah Cannon Research Institute
Nashville
Tennessee
Recruiting
MD Anderson Cancer Center
Houston
Texas
Recruiting
START Mountain Region
West Valley City
Utah
Recruiting
NEXT Virginia
Fairfax
Virginia
Recruiting
West China Hospital, Sichuan University
Chengdu
China
Not Yet Recruiting
Shanghai East Hospital, Tongji University
Shanghai
China
Not Yet Recruiting
Tongji Hospital - Tongji Medical College of HUST
Wuhan
China
Not Yet Recruiting
Centre Leon Berard
Lyon
France
Recruiting
Institut Gustave Roussy
Villejuif
France
Recruiting
Kyoto University Hospital
Kyoto
Japan
Recruiting
National Cancer Center Hospital
Tokyo
Japan
Recruiting
Cancer Institute Hospital of JFCR
Tokyo
Japan
Recruiting
Severance Hospital, Yonsei University Health System
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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