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

NCT ID: NCT02639091

Last Updated: 2019-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-03
• Study Completion Date: 2019-10-17

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.

Conditions

Medical Oncology

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BAY 94-9343 + Pemetrexed + 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)

Group Type: EXPERIMENTAL

BAY 94-9343

Intervention Type: DRUG

In Part 1 of the study, anetumab ravtansine (BAY 94-9343) will be administered by 1-hour IV infusion with a starting dose of 5.5mg/kg(BW) on Day 1 of every treatment cycle (Q3W).

In Part 2 of the study, anetumab ravtansine (BAY 94-9343) will be administered on Day 2 of Cycle 1 and then on Day 1 of Cycle 2 and all subsequent cycles (Q3W)

Pemetrexed

Intervention Type: DRUG

Administered at the dose of 500 mg/m2 body surface area (BSA) by 10-minute IV infusion on Day 1 of every treatment cycle (Q3W) in both parts of the study

Cisplatin

Intervention Type: DRUG

Administered at the dose of 75 mg/m2 (BSA) by 2-hour IV infusion on Day 1 of every treatment cycle (Q3W) in both parts of the study

Interventions

BAY 94-9343

In Part 1 of the study, anetumab ravtansine (BAY 94-9343) will be administered by 1-hour IV infusion with a starting dose of 5.5mg/kg(BW) on Day 1 of every treatment cycle (Q3W).

In Part 2 of the study, anetumab ravtansine (BAY 94-9343) will be administered on Day 2 of Cycle 1 and then on Day 1 of Cycle 2 and all subsequent cycles (Q3W)

Intervention Type: DRUG

Pemetrexed

Administered at the dose of 500 mg/m2 body surface area (BSA) by 10-minute IV infusion on Day 1 of every treatment cycle (Q3W) in both parts of the study

Intervention Type: DRUG

Cisplatin

Administered at the dose of 75 mg/m2 (BSA) by 2-hour IV infusion on Day 1 of every treatment cycle (Q3W) in both parts of the study

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Chicago, Illinois, United States

Bethesda, Maryland, United States

Detroit, Michigan, United States

Charleston, South Carolina, United States

Milan, Lombardy, Italy

Milan, Lombardy, Italy

Countries

United States; Italy

Other Identifiers

2016-003988-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17631

Identifier Type: -

Identifier Source: org_study_id