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

NCT06465069
clinicaltrials.gov
Phase
Phase 1
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Participants
460
clinicaltrials.gov
Lead sponsor
Eli Lilly and Company
clinicaltrials.gov
Start date
2024-07-01
clinicaltrials.gov
Number of sites
39
clinicaltrials.gov

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.
clinicaltrials.gov
Acronym
NEXUS-01
clinicaltrials.gov
Short title
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
clinicaltrials.gov
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
clinicaltrials.gov

Control arm
Open label
clinicaltrials.gov
Registry reports results
No
clinicaltrials.gov
Listing at source
Listed
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Phase
Phase 1
clinicaltrials.gov
Study type
Interventional
clinicaltrials.gov

Completion date
2027-05-01
clinicaltrials.gov
First posted
2024-06-18
clinicaltrials.gov
Registry last updated
2026-10-22
clinicaltrials.gov
Primary completion date
2027-05-01
clinicaltrials.gov
Start date
2024-07-01
clinicaltrials.gov

Participants
460
clinicaltrials.gov
Participant count basis
Estimated
clinicaltrials.gov
Planned participants
460
clinicaltrials.gov
Protocol amendments
7
clinicaltrials.gov
Number of sites
39
clinicaltrials.gov

Data monitoring committee
Yes
clinicaltrials.gov
Registry sponsor category
Industry
clinicaltrials.gov
Lead sponsor
Eli Lilly and Company
clinicaltrials.gov
Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT06465069
clinicaltrials.gov
ClinicalTrials.gov ID
NCT06465069
clinicaltrials.gov
Registry record
Open registry record
clinicaltrials.gov

Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Phase 1a: To determine the recommended phase 2 dose (RP2D) optimal dose(s) of LY4052031

    Timeframe: Cycle 1 (21 Days)

    Number of participants with dose-limiting toxicities (DLTs)

  2. Phase 1b: To assess the antitumor activity of LY4052031 as monotherapy or in combination with pembrolizumab: Overall response rate (ORR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)

  1. To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin)

    Timeframe: Cycle 1 (21 Days)

    PK: Cmin of LY4052031

  2. To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC)

    Timeframe: Cycle 1 (21 Days)

    PK: AUC of LY4052031

  3. To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Overall response rate (ORR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1))

  4. To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Duration of response (DOR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    DOR per investigator assessed RECIST 1.1

  5. To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Time to response (TTR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    TTR per investigator assessed RECIST 1.1

  6. To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Progression free survival (PFS)

    Timeframe: Up to Approximately 48 Months or 4 Years

    PFS per investigator assessed RECIST 1.1

  7. To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Disease control rate (DCR)

    Timeframe: Up to Approximately 48 Months or 4 Years

    DCR per investigator assessed RECIST 1.1

  8. To evaluate the preliminary antitumor activity of LY4052031 monotherapy or in combination with pembrolizumab: Overall survival (OS)

    Timeframe: Up to Approximately 48 Months or 4 Years

    OS per investigator assessed RECIST 1.1

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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/B/D: 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.
    • Cohort D: Treatment-naive for locally advanced or metastatic urothelial cancer.

  • Prior enfortumab vedotin specific requirements:

    • Cohorts A1/A2/C/D: 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)
    • Measurable disease is required as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) for all Cohorts. Cohort A1 may permit non-measurable disease 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

  • 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 and/or clinically significant 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 associated with enfortumab vedotin that required treatment discontinuation
  • Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
Sources for eligibility
clinicaltrials.gov

  • City of Hope National Medical CenterDuarte, United StatesRecruiting
  • University of California, San Diego (UCSD) - Moores Cancer CenterLa Jolla, United StatesRecruiting
  • UCLA Department of Medicine-Hematology/OncologyLos Angeles, United StatesRecruiting
  • Sarah Cannon Research Institute at HealthOneDenver, United StatesRecruiting
  • Florida Cancer Specialists and Research InstituteSt. Petersburg, United StatesCompleted
  • Emory UniversityAtlanta, United StatesRecruiting
  • University of Chicago HospitalChicago, United StatesRecruiting
  • IU Simon Cancer CenterIndianapolis, United StatesNot yet recruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • START Midwest Cancer and Hematology Centers of W MichiganGrand Rapids, United StatesRecruiting
  • Washington University School of Medicine in St. LouisSt Louis, United StatesRecruiting
  • NYU Langone Medical Center - Perlmutter Cancer Center (NYU Cancer Institute)New York, United StatesRecruiting
  • Icahn School of Medicine at Mount SinaiNew York, United StatesRecruiting
  • Columbia University Irving Medical CenterNew York, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • University Hospitals Cleveland Medical CenterCleveland, United StatesRecruiting
  • Sarah Cannon Research InstituteNashville, United StatesRecruiting
  • Tennessee Oncology PLLCNashville, United StatesNot yet recruiting
  • University of Texas MD Anderson Cancer CenterHouston, United StatesRecruiting
  • South Texas Accelerated Research Therapeutics (START)San Antonio, United StatesRecruiting
  • University of Utah - Huntsman Cancer InstituteSalt Lake City, United StatesRecruiting
  • START Mountain RegionWest Valley City, United StatesRecruiting
  • St Vincent's HospitalDarlinghurst, AustraliaRecruiting
  • Linear Clinical ResearchNedlands, AustraliaRecruiting
  • Beijing Cancer hospitalBeijing, ChinaRecruiting

And 14 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2024-512927-36-00
  • J5I-OX-JZYA
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (15)

Targets (1)