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NCT Number: NCT06465069

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

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.

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Key information

Conditions

Metastatic Solid Tumor Adnexal Diseases Advanced Solid Tumor Bladder Cancer Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Cervical Cancer Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Esophageal Cancer Esophageal Diseases Esophageal Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Gonadal Disorders Head and Neck Neoplasms Head and Neck Squamous Cell Carcinoma Lung Diseases Lung Neoplasms Male Urogenital Diseases Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplastic Processes Non-small Cell Lung Cancer Ovarian Cancer Ovarian Diseases Ovarian Neoplasms Pancreatic Cancer Pancreatic Diseases Pancreatic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Prostate Cancer Prostatic Diseases Prostatic Neoplasms Recurrent Solid Tumor Renal Pelvis Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Squamous Cell Carcinoma of Head and Neck Thoracic Neoplasms Triple Negative Breast Cancer Triple Negative Breast Neoplasms Ureteral Diseases Ureteral Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasm Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

St Vincent's Hospital, Darlinghurst, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)
  • 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

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 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 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

Treatment and study plan

LY4052031

Drug

Intravenous

Primary outcomes

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

    Time frame: Cycle 1 (21 Days)

    Number of participants with dose-limiting toxicities (DLTs)

  2. Phase 1b: To assess the antitumor activity of LY4052031 Monotherapy: Overall response rate (ORR)

    Time frame: Up to Approximately 48 Months or 4 Years

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

Secondary outcomes

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

    Time frame: Cycle 1 (21 Days)

    PK: Cmin of LY4052031

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

    Time frame: Cycle 1 (21 Days)

    PK: AUC of LY4052031

  3. To evaluate the preliminary antitumor activity of LY4052031: Overall response rate (ORR)

    Time frame: 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: Duration of response (DOR)

    Time frame: Up to Approximately 48 Months or 4 Years

    DOR per investigator assessed RECIST 1.1

  5. To evaluate the preliminary antitumor activity of LY4052031: Time to response (TTR)

    Time frame: Up to Approximately 48 Months or 4 Years

    TTR per investigator assessed RECIST 1.1

  6. To evaluate the preliminary antitumor activity of LY4052031: Progression free survival (PFS)

    Time frame: Up to Approximately 48 Months or 4 Years

    PFS per investigator assessed RECIST 1.1

  7. To evaluate the preliminary antitumor activity of LY4052031: Disease control rate (DCR)

    Time frame: Up to Approximately 48 Months or 4 Years

    DCR per investigator assessed RECIST 1.1

  8. To evaluate the preliminary antitumor activity of LY4052031: Overall survival (OS)

    Time frame: Up to Approximately 48 Months or 4 Years

    OS per investigator assessed RECIST 1.1

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study 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

Acronym: NEXUS-01

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Jun 18, 2024
Registry last updated
Jul 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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