Clinical trial NCT06238479: A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors
Official title: A Phase 1 Trial Investigating LY4101174, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Recurrent, Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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 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)
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-02-02
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This is a Phase 1a/1b multicenter, open-label study in participants with select advanced or metastatic solid tumors. 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.

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 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 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

Primary outcomes:
measure: Phase 1a: To determine the recommended dose of LY4101174
timeFrame: First 2 Cycles (28 days)
measure: Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4101174
timeFrame: First 2 Cycles (28 days)
measure: Phase 1b: To assess the antitumor activity of LY4101174 Monotherapy: Overall response rate (ORR)
timeFrame: Up to Approximately 48 Months or 4 Years
Secondary outcomes:
measure: To characterize the pharmacokinetics (PK) properties of LY4101174: Minimum Plasma Concentration (Cmin)
timeFrame: First 4 cycles (56 days)
measure: To characterize the PK properties of LY4101174: Area under the concentration versus time curve (AUC)
timeFrame: First 4 cycles (56 days)
measure: To evaluate the preliminary antitumor activity of LY4101174: Overall response rate (ORR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4101174: Duration of response (DOR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4101174: Time to response (TTR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4101174: Progression free survival (PFS)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4101174: Disease control rate (DCR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4101174: Overall survival (OS)
timeFrame: Up to Approximately 48 Months or 4 Years
Other outcomes:
Locations:
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Mineola
country: United States
facility: Perlmutter Cancer Center at NYU Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: Kurralta Park
country: Australia
facility: Icon Cancer Centre Kurralta Park
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
state: Bruxelles-Capitale, Région de
city: Lille
country: France
facility: Centre Oscar Lambret
state: Nord-Pas-de-Calais
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe
state: Strasbourg, Alsace
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Koto City
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: