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

NCT06238479 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 18836J5A-OX-JZWA2023-509867-26-00LOXO-ENC-23001
• Study Type: interventional
• Target: 490
• Locations: 7 countries
• Sites: 28

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.

Conditions

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

Keywords

Bladder Cancer; Bladder Neoplasm; Bladder Urothelial Carcinoma; Urinary Bladder Cancer; Urinary Tract Cancer; Urothelial Neoplasms; Renal Pelvis Cancer; Ureter Cancer; Nectin-4; Antibody Drug Conjugate (ADC)

Outcome Measures

Primary Outcomes (3)

• Phase 1a: To determine the recommended dose of LY4101174

  Number of participants with dose-limiting toxicities (DLTs)

  First 2 Cycles (28 days)

• 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)

• 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 Outcomes (8)

• To characterize the pharmacokinetics (PK) properties of LY4101174: Minimum Plasma Concentration (Cmin)

  First 4 cycles (56 days)

• To characterize the PK properties of LY4101174: Area under the concentration versus time curve (AUC)

  First 4 cycles (56 days)

• To evaluate the preliminary antitumor activity of LY4101174: Overall response rate (ORR)

  Up to Approximately 48 Months or 4 Years

• To evaluate the preliminary antitumor activity of LY4101174: Duration of response (DOR)

  Up to Approximately 48 Months or 4 Years

• To evaluate the preliminary antitumor activity of LY4101174: Time to response (TTR)

  Up to Approximately 48 Months or 4 Years

Study Arms (3)

LY4101174 (Dose-escalation, Cohort A1)

EXPERIMENTAL

Escalating doses of LY4101174 administered intravenously (IV).

Drug: LY4101174

LY4101174 (Dose-optimization, Cohort A2)

EXPERIMENTAL

Comparing 2 or more doses (evaluated during dose escalation) of LY4101174 administered IV.

Drug: LY4101174

LY4101174 (Dose-expansion, Cohort B1, B2, C1-C5)

EXPERIMENTAL

LY4101174 administered IV.

Drug: LY4101174

Interventions

LY4101174 DRUG

Intravenous

LY4101174 (Dose-escalation, Cohort A1); LY4101174 (Dose-expansion, Cohort B1, B2, C1-C5); LY4101174 (Dose-optimization, Cohort A2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 and/or clinically significant bleeding
• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (28)

AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390-8884, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229-3307, United States

Location

Austin Health

Heidelberg, 3084, Australia

Location

Icon Cancer Centre Kurralta Park

Kurralta Park, 5037, Australia

Location

Institut Jules Bordet

Anderlecht, 1070, Belgium

Location

Peking University First Hospital

Beijing, 100034, China

Location

Hunan Cancer Hospital

Changsha, 410013, China

Location

Shanghai East Hospital

Shanghai, 200433, China

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

CHU Strasbourg-Hautepierre

Strasbourg, 67098, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

National Cancer Center Hospital

Chūōku, 104-0045, Japan

Location

National Cancer Center Hospital East

Kashiwa, 277-8577, Japan

Location

The Cancer Institute Hospital of JFCR

Kōtō City, 135-8550, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Related Links

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

MeSH Terms

Conditions

Neoplasm Metastasis; Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Esophageal Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prostatic Neoplasms; Urologic Neoplasms; Ureteral Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Ureteral Diseases

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Only the dose optimization cohort is randomized.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: February 2, 2024
• Study Start: March 5, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); FR (5); ES (4); AU (2); JP (4); CN (3); US (9)