Breast Cancer
Conditions
Keywords
NECTIN4, Zelenectide pevedotin, HR+/HER2-negative, TNBC, Chemotherapy, Duravelo-3, Advanced Breast Cancer
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).
Interventions
DRUGZelenectide pevedotin (BT8009)
Participants will receive zelenectide pevedotin on Days 1, and 8 of every 21-day cycle.
Sponsors
BicycleTx Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors per RECIST version 1.1 as assessed by the Investigator | Up to approximately 3 years | Percentage of participants with either a confirmed complete response (CR) or partial response (PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs) | Up to approximately 3 years | 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. |
| 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 disease progression assessed by the Investigator 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 |
| 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 disease progression per RECIST v1.1 as assessed by the Investigator, or to death (due to any cause), whichever occurs first. |
| 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). |
| 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 documentation of disease progression. |
Countries
Australia, Belgium, France, Italy, Spain, United Kingdom, United States
Outcome results
None listed