A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors

Prostate Cancer Clinical Trial

Official title:

A Phase 1 Trial Investigating LY4101174, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Recurrent, Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06238479
• Other study ID #: LOXO-ENC-23001
• Secondary ID: J5A-OX-JZWA2023-
• Status: Recruiting
• Phase: Phase 1
• Start date: March 5, 2024
• Est. completion date: March 4, 2027

Study information

• Verified date: May 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, LY4101174, is safe, tolerable and effective in participants with 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.

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 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 information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: March 4, 2027
• Est. primary completion date: August 26, 2026
• 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 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 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
• 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
• Recurrence
• 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:
• LY4101174
Intravenous

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina Medical Center	Chapel Hill	North Carolina
United States	UT Southwestern Medical Center	Dallas	Texas
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	Washington University School of Medicine	Saint Louis	Missouri
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 dose of LY4101174	Number of participants with dose-limiting toxicities (DLTs)	First 2 Cycles (28 days)
Primary	Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4101174	Number of participants with DLTs	First 2 Cycles (28 days)
Primary	Phase 1b: To assess the antitumor activity of LY4101174 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 LY4101174: Minimum Plasma Concentration (Cmin)	PK: Cmin of LY4101174	Cycle 1 (14 Days)
Secondary	To characterize the PK properties of LY4101174: Area under the concentration versus time curve (AUC)	PK: AUC of LY4101174	Cycle 1 (14 Days)
Secondary	To evaluate the preliminary antitumor activity of LY4101174: 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 LY4101174: 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 LY4101174: 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 LY4101174: 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 LY4101174: 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 LY4101174: Overall survival (OS)	OS per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years