A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors
- Conditions
- Ovarian CancerRecurrent Solid TumorUrinary Bladder NeoplasmEsophageal CancerRenal Pelvis CancerAdvanced Solid TumorProstate CancerMetastatic Solid TumorTriple Negative Breast CancerBladder Cancer
- Interventions
- Registration Number
- NCT06238479
- Lead Sponsor
- Eli Lilly and Company
- Brief 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 Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
- Detailed Description
This is a Phase 1a/1b multicenter, open-label study in participants with select advanced or metastatic solid tumors. This study is comprised of two phases: Dose Escalation and Dose Optimization (1a), and Dose expansion (1b). Phase 1a will assess the safety, tolerability, and pharmacokinetics of LY4101174 to determine the recommended phase 2 dose (RP2D)/optimal dose. Phase 1b will evaluate efficacy and safety of LY4101174 at the RP2D/optimal dose in 7 expansion cohorts based on tumor type and/or treatment history.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 490
-
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
- 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 or bleeding disorder
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LY4101174 (Dose-optimization, Cohort A2) LY4101174 Comparing 2 or more doses (evaluated during dose escalation) of LY4101174 administered IV. LY4101174 (Dose-escalation, Cohort A1) LY4101174 Escalating doses of LY4101174 administered intravenously (IV). LY4101174 (Dose-expansion, Cohort B1, B2, C1-C5)) LY4101174 LY4101174 administered IV.
- Primary Outcome Measures
Name Time Method 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)
- Secondary Outcome Measures
Name Time Method To characterize the pharmacokinetics (PK) properties of LY4101174: Minimum Plasma Concentration (Cmin) First 4 cycles (56 days) PK: Cmin of LY4101174
To characterize the PK properties of LY4101174: Area under the concentration versus time curve (AUC) First 4 cycles (56 days) PK: AUC of LY4101174
To evaluate the preliminary antitumor activity of LY4101174: 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)
To evaluate the preliminary antitumor activity of LY4101174: Duration of response (DOR) Up to Approximately 48 Months or 4 Years DOR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LY4101174: Time to response (TTR) Up to Approximately 48 Months or 4 Years TTR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LY4101174: Progression free survival (PFS) Up to Approximately 48 Months or 4 Years PFS per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LY4101174: Disease control rate (DCR) Up to Approximately 48 Months or 4 Years DCR per investigator assessed RECIST 1.1
To evaluate the preliminary antitumor activity of LY4101174: Overall survival (OS) Up to Approximately 48 Months or 4 Years OS per investigator assessed RECIST 1.1
Trial Locations
- Locations (25)
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Institut de cancérologie Strasbourg Europe
🇫🇷Strasbourg, Strasbourg, Alsace, France
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Perlmutter Cancer Center at NYU Langone Hospital - Long Island
🇺🇸Mineola, New York, United States
Centre Oscar Lambret
🇫🇷Lille, Nord-Pas-de-Calais, France
Centre Leon Berard
🇫🇷Lyon Cedex 08, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Gustave Roussy
🇫🇷Villejuif Cedex, France
Emory University
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
South Texas Accelerated Research Therapeutics (START)
🇺🇸San Antonio, Texas, United States
Icon Cancer Centre Kurralta Park
🇦🇺Kurralta Park, South Australia, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Institut Jules Bordet
🇧🇪Anderlecht, Bruxelles-Capitale, Région De, Belgium
The Cancer Institute Hospital of JFCR
🇯🇵Koto City, Tokyo, Japan
National Cancer Center Hospital
🇯🇵Chuo-Ku, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain