Study to Assess Clinical Activity of Zelenectide Pevedotin in Participants With Advanced Breast Cancer

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Zelenectide pevedotin (BT8009)

• Registration Number: NCT06840483
• Lead Sponsor: BicycleTx Limited

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-18
• Study First Submitted QC: 2025-02-18
• Study First Posted: 2025-02-21
• Study Start: 2025-03-03
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18
• Primary Completion: 2028-06-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Histologically or cytologically confirmed HR+/HER2-negative endocrine resistant/refractory breast cancer according to ASCO-CAP guidelines and received up to 3 prior lines of non-endocrine therapy for advanced disease.

• 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 but no more than 3 prior lines of systemic therapy for advanced disease.

Exclusion Criteria

• Prior treatment with any antibody drug conjugate 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 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 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 penumonitis requiring ongoing treatment with steriods (>10mg/day of prednisone or equivalent) or other immunosupressive medications.
• Requirement, while on study, for treatment with strong inhiitors 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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A (HR+/HER2-negative breast cancer)	Zelenectide pevedotin (BT8009)	-
Cohort B (TNBC)	Zelenectide pevedotin (BT8009)	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs)	Up to approximately 3 years	Safety will be reported as incidence of treatment-emergent adverse events using NCI CTCAE v5.0 criteria.
Duration of Response (DOR) per RECIST v1.1 as assessed by the Investigator	Up to approximately 3 years	DoR as measured by the time from first documentation of objective response to the first documentation of objective tumor progression or to death (due to any cause), whichever occurs first
Disease Control Rate (DCR) per RECIST v1.1 as assessed by the Investigator	Up to approximately 3 years	Percentage of participants with confirmed CR, PR, or stable disease (SD)
Clinical Benefit Rate (CBR) per RECIST v1.1 as assessed by the Investigator	Up to approximately 3 years	Percentage of participants with CR, PR or SD ≥16 weeks
Overall Survival	Up to approximately 4 years	OS is defined as length of time from the first day of study drug administration (Day 1) to death (due to any cause).
Progression Free Survival (PFS) per RECIST v1.1 as assessed by the Investigator	Up to approximately 3 years	PFS is measured by the time from the first day of study drug administration (Day 1) to the first documentation of objective tumor progression, or to death (due to any cause), whichever occurs first.
Time To Progression (TTP) per RECIST v1.1 as assessed by the Investigator	Up to approximately 4 years	TTP is defined as the time from first dose of study drug administration until first evidence of disease progression

Trial Locations

Locations (5)

Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Compass Oncology - Rose Quarter Cancer Center; 🇺🇸 Portland, Oregon, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology San Antonio; 🇺🇸 San Antonio, Texas, United States

Virginia Oncology Associates; 🇺🇸 Norfolk, Virginia, United States