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

Prostate Cancer Clinical Trial

— NEXUS-01  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06465069
• Other study ID #: LOXO-LNC-24001
• Secondary ID: J5I-OX-JZYA2024-
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: May 2027

Study information

• Verified date: June 2024
• Source: Eli Lilly and Company
• Contact: Patient Advocacy
• Phone: 855-569-6305
• Email: clinicaltrials[@]loxooncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 220
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Bladder Cancer
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Cervical Cancer
• Esophageal Cancer
• Head and Neck Squamous Cell Carcinoma
• Metastatic Solid Tumor
• Neoplasms
• Non-small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Pelvic Neoplasms
• Prostate Cancer
• Recurrent Solid Tumor
• Renal Pelvis Cancer
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urinary Bladder Neoplasm
• Urinary Bladder Neoplasms

Intervention

Drug:
• LY4052031
Intravenous

Locations

Country	Name	City	State
United States	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4052031	Number of participants with dose-limiting toxicities (DLTs)	Cycle 1 (21 Days)
Primary	Phase 1b: To assess the antitumor activity of LY4052031 Monotherapy: Overall response rate (ORR)	ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)	Up to Approximately 48 Months or 4 Years]
Secondary	To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin)	PK: Cmin of LY4052031	Cycle 1 (21 Days)
Secondary	To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC)	PK: AUC of LY4052031	Cycle 1 (21 Days)
Secondary	To evaluate the preliminary antitumor activity of LY4052031: Overall response rate (ORR)	ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1))	Up to Approximately 48 Months or 4 Years
Secondary	To evaluate the preliminary antitumor activity of LY4052031: Duration of response (DOR)	DOR per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
Secondary	To evaluate the preliminary antitumor activity of LY4052031: Time to response (TTR)	TTR per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
Secondary	To evaluate the preliminary antitumor activity of LY4052031: Progression free survival (PFS)	PFS per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
Secondary	To evaluate the preliminary antitumor activity of LY4052031: Disease control rate (DCR)	DCR per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
Secondary	To evaluate the preliminary antitumor activity of LY4052031: Overall survival (OS)	OS per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years