A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors

Official title

A Phase 1a/1b Study of LY4052031, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Advanced or Metastatic Urothelial Carcinoma or Other Solid Tumors

Overview

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.

Interventions

• Drug LY4052031
  Intravenous

Primary outcome measures

• Phase 1a: To determine the recommended phase 2 dose (RP2D) optimal dose(s) of LY4052031 [Time frame: Cycle 1 (21 Days)]
• Phase 1b: To assess the antitumor activity of LY4052031 Monotherapy: Overall response rate (ORR) [Time frame: Up to Approximately 48 Months or 4 Years]

Secondary outcome measures (8)

• To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin) [Time frame: Cycle 1 (21 Days)]
• To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC) [Time frame: Cycle 1 (21 Days)]
• To evaluate the preliminary antitumor activity of LY4052031: Overall response rate (ORR) [Time frame: Up to Approximately 48 Months or 4 Years]
• To evaluate the preliminary antitumor activity of LY4052031: Duration of response (DOR) [Time frame: Up to Approximately 48 Months or 4 Years]
• To evaluate the preliminary antitumor activity of LY4052031: Time to response (TTR) [Time frame: Up to Approximately 48 Months or 4 Years]
• To evaluate the preliminary antitumor activity of LY4052031: Progression free survival (PFS) [Time frame: Up to Approximately 48 Months or 4 Years]
• To evaluate the preliminary antitumor activity of LY4052031: Disease control rate (DCR) [Time frame: Up to Approximately 48 Months or 4 Years]
• To evaluate the preliminary antitumor activity of LY4052031: Overall survival (OS) [Time frame: Up to Approximately 48 Months or 4 Years]

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, HNSCC (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)
• Measurable disease is required as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) for all Cohorts. Cohort A1 may permit non-measurable disease 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 and/or clinically significant 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 22 centers

• City of Hope National Medical Center — Duarte
• University of California, San Diego (UCSD) - Moores Cancer Center — La Jolla
• UCLA Department of Medicine-Hematology/Oncology — Los Angeles
• Sarah Cannon Research Institute at HealthOne — Denver
• Florida Cancer Specialists and Research Institute — St. Petersburg
• University of Chicago Hospital — Chicago
• IU Simon Cancer Center — Indianapolis
• Massachusetts General Hospital — Boston
• … and 14 more centers

Japan · 4 centers

• National Cancer Center Hospital — Chūōku
• National Cancer Center Hospital East — Kashiwa, Chiba
• The Cancer Institute Hospital of JFCR — Kōtō City
• Aichi Cancer Center Hospital — Nagoya

Spain · 4 centers

• Catalan Institute of Oncology Duran i Reynals Hospital — Barcelona
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Madrid Norte Sanchinarro — Madrid
• Hospital Universitario Virgen Del Rocio — Seville

China · 3 centers

• Beijing Cancer hospital — Beijing
• Sun Yat-sen University Cancer Center — Guangzhou
• Renji Hospital, Shanghai Jiaotong University School of Medicine — Shanghai

Australia · 2 centers

• St Vincent's Hospital — Darlinghurst
• Linear Clinical Research — Nedlands

United Kingdom · 2 centers

• St Bartholomew's Hospital — London
• The Christie NHS Foundation Trust — Manchester

France · 1 center

• Institut Gustave Roussy (Igr) — Villejuif

South Korea · 1 center

• Asan Medical Center — Seoul

Identifiers

NCT: NCT06465069 · 18882 · 2024-512927-36-00 · J5I-OX-JZYA · LOXO-LNC-24001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗