Metastatic Solid TumorRecurrent Solid TumorAdvanced Solid TumorUrinary Bladder NeoplasmTriple Negative Breast CancerNon-small Cell Lung CancerEsophageal CancerPancreatic CancerOvarian CancerCervical CancerHead and Neck Squamous Cell CarcinomaProstate CancerRenal Pelvis CancerBladder Cancer
Investigational drug(s) / intervention(s)
LY4101174
LY4101174: Intravenous
Study summary
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with select advanced or metastatic solid tumors. The study is conducted in two parts - phase 1a (dose-escalation, dose-optimization) and phase 1b (dose-expansion). The study will last up to approximately 4 years. Eligible patients will have the option to continue taking study drug after the study is complete.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Have one of the following solid tumor cancers:
* Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
* Cohort A2/B1/B2: urothelial carcinoma
* Cohort C1: triple negative breast cancer
* Cohort C2: non-small cell lung cancer
* Cohort C3: ovarian or fallopian tube cancer
* Cohort C4: cervical cancer
* Cohort C5: head and neck squamous cell carcinoma
* Prior Systemic Therapy Criteria:
* Cohort A1/C1-5: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
* Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* Prior enfortumab vedotin specific requirements:
* Cohorts A1/A2/C1-5: prior treatment with enfortumab vedotin is allowed, but not required
* Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting
* Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.
* Measurability of disease
* Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
* Cohorts A2, B1, B2, C1-5: measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations
Exclusion Criteria:
* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Current of history of intestinal obstruction in the previous 3 months
* Recent thromboembolic event and/or clinically significant bleeding
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
* History of pneumonitis/interstitial lung disease
* History of Grade ≥3 skin toxicity when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
* Individual with active uncontrolled infection
Primary outcome measure(s)
Phase 1a: To determine the recommended dose of LY4101174 — First 2 Cycles (28 days) Number of participants with dose-limiting toxicities (DLTs)
Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4101174 — First 2 Cycles (28 days) Number of participants with DLTs
Phase 1b: To assess the antitumor activity of LY4101174 Monotherapy: Overall response rate (ORR) — Up to Approximately 48 Months or 4 Years ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Trial sites (28)
Facility
City
Region
Status
AdventHealth Orlando
Orlando
Florida
Emory University
Atlanta
Georgia
Massachusetts General Hospital
Boston
Massachusetts
Washington University School of Medicine
St Louis
Missouri
Perlmutter Cancer Center at NYU Langone Hospital - Long Island
Mineola
New York
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York
New York
Memorial Sloan Kettering Cancer Center
New York
New York
UT Southwestern Medical Center
Dallas
Texas
South Texas Accelerated Research Therapeutics (START)
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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