Phase II Anetumab Ravtansine as 2nd Line Treatment for Malignant Pleural Mesothelioma (MPM)

• ClinicalTrials.gov Identifier: NCT02610140
• Recruitment Status: Completed
• First Posted: November 20, 2015
• Last Update Posted: September 11, 2019
• Sponsor: Bayer
• Collaborator: ImmunoGen and MorphoSys
• Information provided by (Responsible Party): Bayer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Drug: Anetumab ravtansine (BAY 94-9343); Drug: Vinorelbine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 248 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 3, 2015
• Actual Primary Completion Date: May 31, 2017
• Actual Study Completion Date: July 2, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: BAY 94-9343; Drug Anetumab ravtansine given Intravenously (IV)	Drug: Anetumab ravtansine (BAY 94-9343); Starting dose: 6.5 mg/kg administered as IV infusion over 1 h every 3 weeks until disease progression or treatment withdrawal for any reason. Dose reductions are permitted.
Active Comparator: Vinorelbine; Drug Vinorelbine given Intravenously	Drug: Vinorelbine; Starting dose: 30mg/m² administered as an IV infusion over 6 to 10 min every week until disease progression or treatment withdrawal for any reason. Dose reductions are permitted per standard practise.

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: Approx. 22 months ]
   Defined as time from randomization until disease progression or death. Patients not experiencing death or progression will be censored at the last tumor assessment.

Secondary Outcome Measures :

1. Overall survival (OS) [ Time Frame: Approx. 42 months ]
   Defined as time from randomization until death from any cause. Patients lost to follow-up or alive at the time of analysis will be censored at the last known alive date.
2. Time to worsening of symptoms characteristic of mesothelioma [ Time Frame: Approx. 22 months ]
   Defined as time from randomization to first worsening of symptoms characteristic of mesothelioma per the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma (MDASI-MPM). Patients who died, were lost to follow-up, or ended MDASI-MPM assessments without confirmed worsening of symptoms will be censored at the date of their last MDASI-MPM assessment with a non-missing total subset score.
3. Time to worsening of pain [ Time Frame: Approx. 22 months ]
   Defined as time from randomization to first worsening of pain per the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma (MDASI-MPM). Patients who died, were lost to follow-up, or ended MDASI-MPM assessments without confirmed worsening of pain will be censored at the date of their last MDASI-MPM assessment with a non-missing pain score.
4. Improvement of symptoms characteristic of mesothelioma [ Time Frame: Approx. 22 months ]
   Improvement occurs if best change from baseline in total subset score per the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma (MDASI-MPM) meets improvement criteria. Improvement must be confirmed by a second MDASI-MPM assessment.
5. Improvement of pain [ Time Frame: Approx. 22 months ]
   Improvement occurs if best change from baseline in pain score per the MD Anderson Symptom Inventory-Malignant Pleural Mesothelioma (MDASI-MPM) meets improvement criteria. Improvement must be confirmed by a second MDASI-MPM assessment.
6. Objective response [ Time Frame: Approx. 22 months ]
   A patient is a responder if the patient's best confirmed tumor response on-study of (complete response) CR or PR, as determined by the central radiological reviewer per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for MPM.
7. Duration of response (DOR) [ Time Frame: Approx. 42 months ]
   Defined in responders as time from first documentation of tumor response (CR or PR) per mRECIST criteria to disease progression or death, as determined by central radiological reviewer.
8. Treatment emergent adverse events as a measure of safety and tolerability [ Time Frame: Approx. 22 months ]
9. Serious adverse events as a measure of safety and tolerability [ Time Frame: Approx. 22 months ]
10. Disease control [ Time Frame: Approx. 22 months ]
    A patient experiences disease control if the patient's best response on-study confirmed tumor response of CR or PR or a tumor response of SD, as determined by the central radiological reviewer per mRECIST criteria
11. Durable Response [ Time Frame: Approx. 42 months ]
    A patient experiences durable response if the patient is Defined in responders as a responder with a duration of response of 180 days or more as determined by the central radiological reviewer.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 > 2.
• Pre-existing cardiac conditions

Contacts and Locations

  Show 75 Study Locations

Sponsors and Collaborators

Bayer

ImmunoGen and MorphoSys

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02610140 History of Changes
• Other Study ID Numbers: 15743; 2012-003650-88 ( EudraCT Number )
• First Posted: November 20, 2015
• Last Update Posted: September 11, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Vinorelbine; Maytansine; Immunoconjugates; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Physiological Effects of Drugs