Clinical trial NCT06465069: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
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)
Triple Negative Breast Cancer (TNBC)
Non-small Cell Lung Cancer (NSCLC)
Head and Neck Squamous Cell Carcinoma (HNSCC)
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-06-18
Enrollment: 420
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, 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.

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)
  * 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

Primary outcomes:
measure: Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4052031
timeFrame: Cycle 1 (21 Days)
measure: Phase 1b: To assess the antitumor activity of LY4052031 Monotherapy: Overall response rate (ORR)
timeFrame: Up to Approximately 48 Months or 4 Years]
Secondary outcomes:
measure: To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin)
timeFrame: Cycle 1 (21 Days)
measure: To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC)
timeFrame: Cycle 1 (21 Days)
measure: To evaluate the preliminary antitumor activity of LY4052031: Overall response rate (ORR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4052031: Duration of response (DOR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4052031: Time to response (TTR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4052031: Progression free survival (PFS)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4052031: Disease control rate (DCR)
timeFrame: Up to Approximately 48 Months or 4 Years
measure: To evaluate the preliminary antitumor activity of LY4052031: Overall survival (OS)
timeFrame: Up to Approximately 48 Months or 4 Years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthOne
state: Colorado
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest Cancer and Hematology Centers of W Michigan
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute
state: Utah
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Villejuif
country: France
facility: Institut Gustave Roussy (Igr)
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Koto City
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul-teukbyeolsi [Seoul]
city: Barcelona
country: Spain
facility: Catalan Institute of Oncology Duran i Reynals Hospital
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Madrid Norte Sanchinarro
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
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: