Phase Ib Study of Anetumab Ravtansine in Combination With Pemetrexed and Cisplatin in Mesothelin-expressing Solid Tumors

Phase 1

Completed

• Conditions: Medical Oncology
• Interventions: Drug: BAY 94-9343; Drug: Pemetrexed; Drug: Cisplatin

• Registration Number: NCT02639091
• Lead Sponsor: Bayer

Brief Summary

Determine the safety, tolerability and maximum tolerated dose of anetumab ravtansine (BAY 94-9343) in combination with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 in subjects with mesothelin-expressing predominantly epithelial mesothelioma or nonsquamous non-small-cell lung cancer.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2015-11-30
• Study First Submitted QC: 2015-12-21
• Study First Posted: 2015-12-24
• Study Start: 2016-02-03
• Primary Completion: 2018-05-23
• Status Verified: 2019-10
• Study Completion: 2019-10-17
• Last Update Submitted: 2019-11-06
• Last Update Posted: 2019-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Subjects may be male or female, and must be aged =/>18 years on the date of signing the informed consent form.
• Subjects must have histologically confirmed, unresectable, locally advanced or metastatic pleural or peritoneal predominantly (>50% of tumor component) epithelial mesothelioma or nonsquamous non-small-cell lung cancer (NSCLC). Both chemotherapy-naive and previously treated subjects will be eligible; however, newly diagnosed NSCLC subjects eligible for FDA-approved therapies should have received the same before enrollment (e.g. subjects with epidermal growth factor receptor [EGFR]-mutated and anaplastic lymphoma kinase [ALK]-translocated NSCLC should have received FDA-approved targeted therapies).
• Subjects must have at least 1 measurable or evaluable tumor lesion according to RECIST 1.1 (for nonsquamous NSCLC) or mRECIST (for epithelial pleural mesothelioma). Subjects with resected primary tumors who have documented metastases are eligible.
• Subjects must have a life expectancy of at least 12 weeks.
• Subjects must have ECOG (Eastern Cooperative Oncology Group performance Status of 0 or 1
• Subjects must have adequate bone marrow, liver, kidney, and coagulation functions.

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Exclusion Criteria

• Subjects who have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, or any previous cancer curatively treated >3 years before the start of study Treatment.
• Subjects who have a history or current evidence of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE (Common Terminology Criteria for Adverse Events) Grade ≥2 within 4 weeks before the start of study Treatment.
• Subjects who have new or progressive brain or meningeal or spinal metastases.
• Subjects who have a history or current evidence of uncontrolled cardiovascular disease i.e. NYHA (New York Heart Association) Class III or IV.
• Subjects who have a history or current evidence of uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at screening despite optimal medical management.
• Subjects who have a history or current evidence of malignant biliary obstruction requiring biliary stent.
• Subjects who have had solid organ or bone marrow Transplantation.
• Subjects who have a history of hypersensitivity to any of the study drugs or their excipients, or a history of severe hypersensitivity to any other Antigen.
• Subjects who have a history of human immunodeficiency virus (HIV) infection or subjects who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
• Subjects who have an active clinically serious infection of CTCAE Grade ≥2 or non-healing wound unrelated to the primary Tumor.
• Subjects who have received systemic cancer therapy, radiotherapy, investigational drug treatment outside of this study within 4 weeks before the start of study treatment, granulocyte colony stimulating factors, (G-CSF) or granulocyte macrophage-stimulating factors (GM-CSF), erythropoietin-stimulating agents within 3 weeks before the start of general screening, drugs with known renal toxicity and strong cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers within 2 weeks before the treatment.
• Subjects who have started oral or parenteral anticoagulation therapy within 2 weeks before the start of anetumab ravtansine until end of treatment visit.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BAY 94-9343 + Pemetrexed + Cisplatin	BAY 94-9343	Investigating the combination of anetumab ravtansine (BAY 94-9343) with Pemetrexed (500 mg/m2) and Cisplatin (75 mg/m2) in Part 1 (dose escalation cohorts) and Part 2 (two MTD expansion cohorts)
BAY 94-9343 + Pemetrexed + Cisplatin	Pemetrexed	Investigating the combination of anetumab ravtansine (BAY 94-9343) with Pemetrexed (500 mg/m2) and Cisplatin (75 mg/m2) in Part 1 (dose escalation cohorts) and Part 2 (two MTD expansion cohorts)
BAY 94-9343 + Pemetrexed + Cisplatin	Cisplatin	Investigating the combination of anetumab ravtansine (BAY 94-9343) with Pemetrexed (500 mg/m2) and Cisplatin (75 mg/m2) in Part 1 (dose escalation cohorts) and Part 2 (two MTD expansion cohorts)

Primary Outcome Measures

Name	Time	Method
Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability	Up to 2 years
Maximum tolerated dose (MTD)	Up to 2 years	MTD is defined as the highest dose of oral anetumab ravtansine (BAY 94-9343) administered in combination with IV pemetrexed and cisplatin that can be given such that not more than 1 of 6 subjects at a given dose level experience a DLT (dose-limiting toxicity).

Secondary Outcome Measures

Name	Time	Method
Plasma concentrations of anetumab ravtansine (BAY 94-9343), pemetrexed and cisplatin	- BAY 94-9343: C1D1,D2,D3,D8,D15, C2D1, C3D1,D2,D3,D8,D15, C4D1, C6D1 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first - Pemetrexed: C1D1, D2, D3 - Cisplatin: C1D1, D2, D3	C (treatment cycle), D (day); Each cycle is defined as a period of 21 days
Tumor response evaluation following mRECIST criteria to determine the number of patients with CR, PR, SD or PD	Baseline, every 8 weeks up to cycle 12; then every 12 weeks from cycle 13 up to 2 years, or until discontinuation of study treatment, whichever comes first	CR (complete response); PR (partial response); SD (stable disease); PD (progressive disease); Each cycle is defined as a period of 21 days
Number of patients with a positive titer of anti-drug antibodies	Day1 of C1, C3, C6 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first	Each cycle is defined as a period of 21 days