Clinical trial NCT02639091: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Medical Oncology
Keywords: Phase 1
Solid tumors
Mesothelioma
Lung cancer
Pemetrexed
Cisplatin
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-12-24
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Up to 2 years
measure: Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability
timeFrame: Up to 2 years
Secondary outcomes:
measure: Plasma concentrations of anetumab ravtansine (BAY 94-9343), pemetrexed and cisplatin
timeFrame: - 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
measure: Tumor response evaluation following mRECIST criteria to determine the number of patients with CR, PR, SD or PD
timeFrame: 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
measure: Number of patients with a positive titer of anti-drug antibodies
timeFrame: Day1 of C1, C3, C6 and subsequent cycles every 3rd cycle up to 2 years or until discontinuation of study treatment, whichever comes first
Other outcomes:
Locations:
city: Chicago
country: United States
state: Illinois
city: Bethesda
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Charleston
country: United States
state: South Carolina
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: