Zelenectide Pevedotin in NECTIN4 Amplified Advanced or Metastatic Non-small Cell Lung Cancer

Phase 2 Study of Zelenectide Pevedotin in Participants With Previously-Treated NECTIN4 Amplified Advanced or Metastatic Non-small Cell Lung Cancer

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Zelenectide pevedotin

• Study Type: Interventional
• Enrollment (Estimated): 73
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75005
    • Institut Curie
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (non-squamous NSCLC)	Drug: Zelenectide pevedotin; Participants will receive zelenectide pevedotin on Days 1, and 8 of every 21-day cycle.; Other Names: BT8009
Experimental: Cohort B (squamous NSCLC)	Drug: Zelenectide pevedotin; Participants will receive zelenectide pevedotin on Days 1, and 8 of every 21-day cycle.; Other Names: BT8009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) assessed by Investigator	Percentage of participants with either a confirmed complete response (CR) or partial response (PR)	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as length of time from the first day of study drug administration (Day 1) to death (due to any cause).	Up to approximately 3 years
Number of participants reporting adverse events (AEs) and abnormalities in laboratory, electrocardiogram (ECG) and vital signs	Safety will be reported as incidence, severity, seriousness, relationship to study treatment, and types of adverse events using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 criteria.	Up to approximately 3 years
Duration of Response (DOR) per RECIST v1.1 assessed by the Investigator	DoR as measured by the time from first documentation of disease progression per RECIST v1.1 or to death (due to any cause), whichever occurs first.	Up to approximately 3 years
Disease Control Rate (DCR) per RECIST v1.1 assessed by the Investigator	Percentage of participants with confirmed CR, PR, or stable disease (SD)	Up to approximately 3 years
Clinical Benefit Rate (CBR) per RECIST v1.1 assessed by the Investigator	Percentage of participants with CR, PR or SD ≥16 weeks	Up to approximately 3 years
Progression Free Survival (PFS) per RECIST v1.1 assessed by the Investigator	PFS is measured by the time from the first day of study drug administration (Day 1) to the first documentation of disease progression, or to death (due to any cause), whichever occurs first.	Up to approximately 3 years
Time to Progression (TTP) per RECIST v1.1 assessed by the Investigator	TTP is defined as the time from first dose of study drug administration until first documentation of disease progression	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: BicycleTx Limited

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): February 28, 2029

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Chemotherapy; Squamous; Non-Squamous; Advanced or Metastatic; Zelenectide pevedotin; NECTIN4
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BT8009-202 (Duravelo-4)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No