A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
Conditions
Metastatic Solid Tumor, Recurrent Solid Tumor, Advanced Solid Tumor, Urinary Bladder Neoplasm, Triple Negative Breast Cancer, Non-small Cell Lung Cancer, Esophageal Cancer, Pancreatic Cancer, Ovarian Cancer, Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Prostate Cancer, Renal Pelvis Cancer, Bladder CancerDrugs
LY4052031Summary
The purpose of this study is to find out whether the study drug, LY4052031, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors including urothelial cancer. 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 advanced or metastatic solid tumor malignancies known to express Nectin 4. This study evaluates an antibody-drug conjugate that binds to the protein nectin-4, which is expressed on certain cancer cells, delivering the drug to the cancer. 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 LY4052031 to determine the recommended phase 2 dose (RP2D)/optimal dose. Phase 1b will evaluate efficacy and safety of LY4052031 at the RP2D/optimal dose in expansion cohorts based on tumor type and/or treatment history.
Locations
8 locations Found with status Recruiting
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Status
- RECRUITING
Central Contacts
- There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
- 13176154559
- [email protected]
Study Director
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eligibility Criteria
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 C: triple negative breast cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, head and neck squamous cell carcinoma, esophageal cancer, pancreatic cancer, or prostate cancer
* Prior Systemic Therapy Criteria:
* Cohort A1/C: 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/C: 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, C: 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 keratitis, and history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* 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
Study Plan
LY4052031 (Dose-escalation, Cohort A1)
EXPERIMENTAL
Escalating doses of LY4052031 administered intravenously (IV).
DRUG:
LY4052031Description:
Intravenous
LY4052031 (Dose-optimization, Cohort A2)
EXPERIMENTAL
Comparing 2 or more doses (evaluated during dose escalation) of LY4052031 administered IV.
DRUG:
LY4052031Description:
Intravenous
LY4052031 (Dose-expansion, Cohort B1, B2, C1)
EXPERIMENTAL
LY4052031 administered IV.
DRUG:
LY4052031Description:
Intravenous
Outcome Measures
Primary Outcome Measures
Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4052031
Phase 1b: To assess the antitumor activity of LY4052031 Monotherapy: Overall response rate (ORR)
Secondary Outcome Measures
To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin)
To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC)
To evaluate the preliminary antitumor activity of LY4052031: Overall response rate (ORR)
To evaluate the preliminary antitumor activity of LY4052031: Duration of response (DOR)
To evaluate the preliminary antitumor activity of LY4052031: Time to response (TTR)
To evaluate the preliminary antitumor activity of LY4052031: Progression free survival (PFS)
To evaluate the preliminary antitumor activity of LY4052031: Disease control rate (DCR)
To evaluate the preliminary antitumor activity of LY4052031: Overall survival (OS)
Timeline
Last Updated
November 20, 2024Start Date
June 18, 2024Today
January 16, 2025Completion Date ( Estimated )
May 1, 2027
Sponsors of this trial
Lead Sponsor
Eli Lilly and Company