Study of Zelenectide Pevedotin in Participants With Advanced Breast Cancer

Phase 2 Study of Zelenectide Pevedotin in Participants With NECTIN4 Amplified Advanced Breast Cancer

This is a global, multicenter, open-label study that aims to assess the efficacy and safety of zelenectide pevedotin in participants with NECTIN4-amplified recurrent, unresectable, or metastatic breast cancer who have received prior therapy (see inclusion criteria below). The study will comprise of 2 cohorts. Cohort A will include participants with hormone receptor positive/ human epidermal growth factor receptor 2 negative [HR+/HER2-] breast cancer, whereas Cohort B will include participants with triple-negative breast cancer (TNBC).

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Zelenectide pevedotin (BT8009)

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• France
  • Toulouse, France, 31059
    • Oncopole Claudius Regaud
• Italy
  • Ancona, Italy, 60126
    • Clinica Oncologica-Azienda Ospedaliero Universitaria delle Marche
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Forli/Cesena
    • Meldola, Forli/Cesena, Italy, 47014
      • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRCCS IRST
• Spain
  • Barcelona, Spain, 08023
    • Hospital Quironsalud Barcelona
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital Beata Maria Ana
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (SKCCC)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Siteman Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center - Main Campus
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97227
      • Compass Oncology - Rose Quarter Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Archival or fresh tumor tissue comprised of TNBC or HR+/HER2-negative invasive breast cancer available for NECTIN4 gene amplification testing.
• Confirmed NECTIN4 gene amplification by an analytically validated clinical trial assay (CTA).
• Measurable disease as defined by RECIST v1.1.
• Life expectancy ≥ 12 weeks.

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤ 1.

  1. Cohort A Specific Inclusion Criteria: Histologically or cytologically confirmed HR+/HER2-negative endocrine resistant/refractory breast cancer according to ASCO-CAP guidelines and received at least 1 and up to 3 prior lines of non-endocrine-based therapy for advanced disease.
  2. Cohort B Specific Inclusion Criteria: Histologically or cytologically confirmed TNBC, including ER-low positive breast cancers (1-10% of cells expressing hormonal receptors by IHC), according to ASCO-CAP guidelines and have received at least 1 and up to 3 prior lines of systemic therapy for advanced disease.

Exclusion Criteria

• Prior treatment with any antibody drug conjugate (ADC) containing an Monomethyl Auristatin E (MMAE) (vedotin) payload or other MMAE-based therapy.
• Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.
• Previously tested HER2-positive (IHC 3+ or ISH+) on prior pathology testing (per ASCO-CAP guidelines).
• 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 drainage procedures (once 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.
• Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors.
• 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 (HR+/HER2-negative breast cancer)	Drug: Zelenectide pevedotin (BT8009); Participants will receive zelenectide pevedotin on Days 1, and 8 of every 21-day cycle.
Experimental: Cohort B (TNBC)	Drug: Zelenectide pevedotin (BT8009); Participants will receive zelenectide pevedotin on Days 1, and 8 of every 21-day cycle.

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 per RECIST version 1.1 as assessed by the 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
Disease Control Rate (DCR) per RECIST v1.1 as 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 as assessed by the Investigator	Percentage of participants with CR, PR or SD ≥16 weeks	Up to approximately 3 years
Overall Survival	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 4 years
Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs)	Safety and tolerability will be reported as incidence, severity, seriousness, relationship, and type of treatment-emergent adverse events, abnormalities in laboratory, electrocardiogram (ECG), vital signs and treatment modifications 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 as assessed by the Investigator	DoR as measured by the time from first documentation of objective response to the first documentation of disease progression assessed by the Investigator or to death (due to any cause), whichever occurs first.	Up to approximately 3 years
Progression Free Survival (PFS) per RECIST v1.1 as 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 per RECIST v1.1 as assessed by the Investigator, or to death (due to any cause), whichever occurs first.	Up to approximately 3 years
Time To Progression (TTP) per RECIST v1.1 as 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 4 years

Collaborators and Investigators

• Sponsor: BicycleTx Limited

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 21, 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: Advanced Breast Cancer; Chemotherapy; TNBC; Zelenectide pevedotin; NECTIN4; HR+/HER2-negative; Duravelo-3
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: BT8009-201 (Duravelo-3); 2024-517868-33-00 (Ctis)

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