Recruiting
Phase 2

Zelenectide Pevedotin

Sponsor:

BicycleTx Limited

Code:

NCT06933329

Conditions

Non-Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zelenectide pevedotin

Study Details

Brief summary:

This is a global, multicenter, open-label study that aims to assess the efficacy and safety of zelenectide pevedotin in participants with previously treated NECTIN4-amplified advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior line of systemic therapy in the advanced/metastatic setting (see inclusion criteria below). The study will comprise of 2 cohorts: Cohort A (non-squamous NSCLC) and Cohort B (squamous NSCLC).

Conditions

Non-Small Cell Lung Cancer

Study ID

NCT06933329

Start date

Jul 18, 2025

Status verified date

Mar, 2026

Completion date

Feb 28, 2029

Anticipated

Primary completion date

Aug 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria

  • Histologically or cytologically confirmed advanced or metastatic NSCLC.

1. Cohort A: Histologically or cytologically confirmed non-squamous NSCLC.
2. Cohort B: Histologically or cytologically confirmed squamous NSCLC.
  • Confirmed NECTIN4 gene amplification by an analytically validated clinical trial assay.
  • Participants must have received at least 1 prior line of systemic therapy in the advanced/metastatic setting.

  • Participants with no known actionable genomic alterations must have received both platinum based therapy and immunotherapy given either sequentially or in combination for advanced/metastatic NSCLC. Must not have received more than 3 prior lines of systemic therapy in the advanced/metastatic setting.
  • Participants with known actionable genomic alterations (eg, EGFR, ALK, BRAF, MET, ROS1, NTRK1/2/3, RET, etc.) are eligible provided they have received or are not candidates for available standard targeted therapy in the advanced/metastatic setting.
  • Measurable disease as defined by RECIST v1.1.
  • Adequate archival or fresh tumor tissue comprised of advanced or metastatic NSCLC should be available for submission to central laboratory, if not provided during prescreening.
  • Life expectancy ≥ 12 weeks.
  • Eastern Cooperative Oncology Group Performance Status of ≤ 1.

Key Exclusion Criteria

  • Evidence of mixed small cell lung cancer (SCLC) and NSCLC histology.
  • Prior treatment with monomethyl auristatin E (MMAE) (vedotin) based therapy.
  • Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.
  • Ongoing clinically significant toxicity (Grade ≥ 2) associated with prior treatment for NSCLC (including radiotherapy or surgery), with the exception of well-controlled immuno-oncology related endocrine disorders on supportive or replacement therapy, and alopecia. (Note: Immunosuppressive therapies should be stopped or tapered down to ≤10 mg/day prednisone or equivalent before first study drug administration.)
  • Active keratitis or corneal ulcerations.
  • Active or untreated central nervous system (CNS) metastases.
  • Uncontrolled diabetes or hypertension.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent draining procedures (monthly or more frequently).
  • Active interstitial lung disease or pneumonitis requiring ongoing treatment with steroids (>10mg/day of prednisone or equivalent) or other immunosuppressive medications; or any prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
  • History of another active malignancy, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other malignancies curatively treated with no evidence of disease for ≥3 years.
  • Known requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (\[cytochrome P450 3A\] CYP3A) including herbal- or food-based inhibitors/inducers.
  • Prior treatment with any systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to first dose of study treatment.

Note: Additional protocol defined Inclusion/Exclusion criteria apply

Study Design

Enrollment

73 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort A (non-squamous NSCLC)

experimental: Cohort B (squamous NSCLC)

Interventions

Zelenectide pevedotin

Participants will receive zelenectide pevedotin on Days 1, and 8 of every 21-day cycle.

Primary outcome measure

  • Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) assessed by Investigator [ Time Frame: Up to approximately 3 years ]

Central Contacts and Locations

Central contacts

BicycleTx Limited

617-945-8155clinicalstudies@bicycletx.com

Locations

Alaska Oncology and Hematology, LLC

Recruiting

Anchorage, Alaska, United States, 99508

University of California, Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

St. Vincent Regional Hospital - Cancer Centers of Montana

Recruiting

Billings, Montana, United States, 59102

Oncology Hematology Care Clinical Trials, LLC

Recruiting

Fairfield, Ohio, United States, 45014

Honickman Center (Thomas Jefferson University)

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Texas Oncology - Central South

Recruiting

Austin, Texas, United States, 78758

Texas Oncology - DFW

Recruiting

Dallas, Texas, United States, 75203

Virginia Cancer Specialists

Recruiting

Arlington, Virginia, United States, 22201

More Information

Sponsor

BicycleTx Limited

Last update posted

Mar 10, 2026

Last verified

Mar, 2026

Keywords

  • NECTIN4
  • Zelenectide pevedotin
  • Advanced or Metastatic
  • NSCLC
  • Chemotherapy
  • Non-Squamous
  • Squamous

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by BicycleTx Limited on 2026-03-10.