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

NCT06933329 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BT8009-202 (Duravelo-4)
• Study Type: interventional
• Target: 73
• Locations: 2 countries
• Sites: 3

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of participants reporting adverse events (AEs) and abnormalities in laboratory, electrocardiogram (ECG) and vital signs

  Up to approximately 3 years

• Duration of Response (DOR) per RECIST v1.1 assessed by the Investigator

  Up to approximately 3 years

• Disease Control Rate (DCR) per RECIST v1.1 assessed by the Investigator

  Up to approximately 3 years

• Clinical Benefit Rate (CBR) per RECIST v1.1 assessed by the Investigator

  Up to approximately 3 years

• Progression Free Survival (PFS) per RECIST v1.1 assessed by the Investigator

  Up to approximately 3 years

Study Arms (2)

Cohort A (non-squamous NSCLC)

EXPERIMENTAL

Drug: Zelenectide pevedotin

Cohort B (squamous NSCLC)

EXPERIMENTAL

Drug: Zelenectide pevedotin

Interventions

Zelenectide pevedotin DRUG

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

Also known as: BT8009

Cohort A (non-squamous NSCLC); Cohort B (squamous NSCLC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed advanced or metastatic NSCLC.
• Cohort A: Histologically or cytologically confirmed non-squamous NSCLC.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BicycleTx Limited: lead

Study Sites (3)

Institut Curie

Paris, 75005, France

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: April 18, 2025
• Study Start: July 18, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): February 28, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); FR (1)