A Randomized, Open-label, Active-controlled, Phase II Study of Intravenous Anetumab Ravtansine (BAY 94-9343) or Vinorelbine in Patients With Advanced or Metastatic Malignant Pleural Mesothelioma Overexpressing Mesothelin and Progressed on First Line Platinum/Pemetrexed-based Chemotherapy
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Bayer
- Enrollment
- 248
- Primary Endpoint
- Progression-free Survival (PFS), [95% CI]
Study Overview
Brief Summary
The main purpose of the 15743 study is to assess efficacy and safety of anetumab ravtansine versus vinorelbine in progression free survival in patients with stage IV mesothelin overexpressing malignant pleural mesothelioma (MPM).
210 eligible patients will be randomized to receive either anetumab ravtansine every three weeks or weekly vinorelbine.
Treatment will continue until centrally confirmed disease progression or until another criterion is met for withdrawal from the study. Patients will enter follow up phase to capture safety and endpoint data as required.
Efficacy will be measured by evaluating progression free survival from randomization. Radiological tumor assessments will be performed at defined time points until the patient's disease progresses.
Blood samples will be collected for safety, pharmacokinetic and biomarker analysis. Archival or fresh biopsy tissue may also be collected for central pathology review and biomarkers.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histological documentation of malignant pleural mesothelioma (MPM) overexpressing mesothelin
- •Unresectable locally advanced or metastatic MPM after locally confirmed progression on 1st line treatment with platinum in combination with pemetrexed.
- •Patients must have measurable disease
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- •Life expectancy of at least 3 months.
- •Adequate bone marrow, liver and renal function
- •Left ventricular ejection fraction (LVEF) ≥ 50% or the lower limit of normal (LLN) according to local institution ranges of normality.
Exclusion Criteria
- •More than 1 previous systemic anti-cancer therapy line
- •Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the investigator in consultation with the ophthalmologist.
- •Brain metastases, meningeal tumours or other metastases in the central nervous system
- •Evidence of history of bleeding diathesis.
- •Ongoing or active infection (bacterial, fungal, or viral) of National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 Grade >
- •Pre-existing cardiac conditions
Arms & Interventions
BAY94-9343
Drug Anetumab ravtansine given Intravenously (IV)
Intervention: Anetumab ravtansine (BAY94-9343) (Drug)
Vinorelbine
Drug Vinorelbine given Intravenously
Intervention: Vinorelbine (Drug)
Outcomes
Primary Outcomes
Progression-free Survival (PFS), [95% CI]
Time Frame: From randomization till approximately 117 PFS events observed, up to approx. 30 months (data cut-off: 31-May-2017)
Progression-free survival (PFS), defined as time from randomization until disease progression according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) for Malignant pleural mesothelioma (MPM) per blinded central radiology review, or death. Only descriptive analysis of OS was repeated in the follow-up period.
Secondary Outcomes
- Overall Survival (OS), [95% CI](Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause; one-sided log-rank test stratified by time to progression (TTP) on first line treatment.)
- Objective Response Rate (ORR)(up to approx. 30 months (data cut-off: 31-May-2017) - Time from randomization until death from any cause.)
- Disease Control Rate (DCR)(Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.)
- Duration of Response (DOR)(Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.)
- Durable Response Rate (DRR)(Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.)
- Percentage of Participants With Confirmed Improvement of Symptoms Characteristic of Mesothelioma(up to approx. 30 months (data cut-off: 31-May-2017))
- Time to Worsening of Symptoms Characteristic of Mesothelioma(up to approx. 30 months (data cut-off: 31-May-2017))
- Time to Worsening of Pain(up to approx. 30 months (data cut-off: 31-May-2017))
- Percentage of Participants With Confirmed Improvement of Pain(Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.)
- Percentage of Participant With Treatment-emergent Adverse Events (TEAEs)(Up to approx. 55 months (data cut-off: 02-Jul-2019) - Time from randomization until 30 days after last treatment (general AEs), or further until death from any cause (selected AEs).)
- Number of Deaths(Up to approx. 40 months (data cut-off: 06-Apr-2018) - Time from randomization until death from any cause.)
- Overall Survival (OS) - Addendum(Up to approx. 55 month (data cut-off: 02-JUL-2019) - Time from randomization until death from any cause)