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

NCT02639091

Description:

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.

Related Conditions:
  • Mesothelioma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title:Phase Ib Study of Anetumab Ravtansine in Combination With Pemetrexed and Cisplatin in Mesothelin-expressing Solid Tumors
  • Official Title:An Open Label Phase Ib Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Maximum Tolerated Dose of Anetumab Ravtansine 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

Clinical Trial IDs

  • ORG STUDY ID: 17631
  • NCT ID: NCT02639091

Trial Conditions

  • Medical Oncology

Trial Interventions

DrugSynonymsArms
BAY 94-9343BAY 94-9343 + Pemetrexed + Cisplatin
PemetrexedBAY 94-9343 + Pemetrexed + Cisplatin
CisplatinBAY 94-9343 + Pemetrexed + Cisplatin

Trial Purpose

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

Trial Arms

NameTypeDescriptionInterventions
BAY 94-9343 + Pemetrexed + CisplatinExperimentalInvestigating the combination of anetumab ravtansine (BAY 94-9343) with Pemetrexed (500 mg/m2) and Cisplatin (75 mg/m2) in a dose escalation/de-escalation cohort (Part1) and an MTD expansion cohort (Part 2)
  • BAY 94-9343
  • Pemetrexed
  • Cisplatin

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 provide sample of archival Tumor tissue (tissue block preferred, at least 5 formalinfixated, paraffin-embedded [FFPE] slides acceptable) collected any time before the General screening.

- Subjects must have positive mesothelin expression in the archival tumor tissue, defined as the mesothelin membrane intensity score of 1+, 2+ or 3+ (on the 0-3 scale) expressed on the membrane of ≥5% of tumor cells.

- 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 >150 mmHg or diastolic blood pressure >95 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, granulocyte colonystimulating factors, (G-CSF) or granulocyte macrophage-stimulating factors (GM-CSF), erythropoietin-stimulating agents, investigational drug treatment outside of this study within 4 weeks before the start of study treatment, drugs with known renal toxicity and strong cytochrome P450 3A4 (CYP3A4) inhibitors or strong CYP3A4 inducers.

- Subjects who have started oral or parenteral anticoagulation therapy within 2 weeks before the start of anetumab ravtansine until end of treatment visit.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:Up to 2 years
Safety Issue:Yes
Description: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

Measure:Plasma concentrations of anetumab ravtansine (BAY 94-9343), pemetrexed and cisplatin
Time Frame:- 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
Safety Issue:No
Description:C (treatment cycle), D (day); Each cycle is defined as a period of 21 days
Measure:Tumor response evaluation following mRECIST criteria to determine the number of patients with CR, PR, SD or PD
Time Frame: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
Safety Issue:No
Description:CR (complete response); PR (partial response); SD (stable disease); PD (progressive disease); Each cycle is defined as a period of 21 days
Measure:Number of patients with a positive titer of anti-drug antibodies
Time Frame:Day1 of C1, C3, C6 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first
Safety Issue:No
Description:Each cycle is defined as a period of 21 days

Trial Keywords

  • Phase 1
  • Solid tumors
  • Mesothelioma
  • Lung cancer
  • Pemetrexed
  • Cisplatin