Clinical trial NCT06840483: Study to Assess Clinical Activity of Zelenectide Pevedotin in Participants With Advanced Breast Cancer
Official title: Phase 2 Study of Zelenectide Pevedotin in Participants With NECTIN4 Amplified Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: NECTIN4
Zelenectide pevedotin
HR+/HER2-negative
TNBC
Chemotherapy
Lead sponsor: BicycleTx Limited
Sponsor class: INDUSTRY
First posted: 2025-02-21
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria

* Archival or fresh tumor tissue comprised of recurrent unresectable or metastatic TNBC or HR+/HER2-negative breast cancer available for NECTIN4 gene amplification testing.
* Confirmed NECTIN4 gene amplification by an analytically validated clinical trial assay.
* Measurable disease as defined by RECIST v1.1.
* Life expectancy ≥ 12 weeks.
* Eastern Cooperative Oncology Group Performance Status of ≤ 2.
* Cohort A Specific 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

Primary outcomes:
measure: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) as assessed by Investigator
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR) per RECIST v1.1 as assessed by the Investigator
timeFrame: Up to approximately 3 years
measure: Disease Control Rate (DCR) per RECIST v1.1 as assessed by the Investigator
timeFrame: Up to approximately 3 years
measure: Clinical Benefit Rate (CBR) per RECIST v1.1 as assessed by the Investigator
timeFrame: Up to approximately 3 years
measure: Overall Survival
timeFrame: Up to approximately 4 years
measure: Progression Free Survival (PFS) per RECIST v1.1 as assessed by the Investigator
timeFrame: Up to approximately 3 years
measure: Time To Progression (TTP) per RECIST v1.1 as assessed by the Investigator
timeFrame: Up to approximately 4 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital - Yale Cancer Center
state: Connecticut
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Portland
country: United States
facility: Compass Oncology - Rose Quarter Cancer Center
state: Oregon
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: San Antonio
country: United States
facility: Texas Oncology San Antonio
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
References: