Clinical trial NCT06933329: Zelenectide Pevedotin in NECTIN4 Amplified Advanced or Metastatic Non-small Cell Lung Cancer
Official title: Phase 2 Study of Zelenectide Pevedotin in Participants With Previously-Treated NECTIN4 Amplified Advanced or Metastatic Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: NECTIN4
Zelenectide pevedotin
Advanced or Metastatic
NSCLC
Chemotherapy
Lead sponsor: BicycleTx Limited
Sponsor class: INDUSTRY
First posted: 2025-04-18
Enrollment: 73
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 previously treated NECTIN4-amplified advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one line of 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).


Eligibility criteria: Key Inclusion Criteria

* Histologically or cytologically confirmed advanced or metastatic NSCLC.

  1. Cohort A: Histologically or cytologically confirmed non-squamous NSCLC.
  2. Cohort B: Histologically or cytologically confirmed squamous NSCLC.
* Confirmed NECTIN4 gene amplification by an analytically validated clinical trial assay.
* Participants must not have received more than 3 prior lines 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.
  * Those with known actionable genomic alterations (eg, EGFR, ALK, BRAF, MET, ROS1, NTRK1/2/3, RET) 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.

Key Exclusion Criteria

* 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.
* 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 or another active malignancy that would interfere with the safety or efficacy evaluation of the clinical study.
* Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (\[cytochrome P450 3A\] 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 abnormalities in laboratory, electrocardiogram (ECG) and vital signs
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: Progression Free Survival (PFS) per RECIST v1.1 as assessed by the Investigator
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Time to Progression (TTP) per RECIST v1.1 as assessed by the Investigator
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
Study officials:
References: