Medical Oncology
Conditions
Keywords
Phase 1, Solid tumors, Mesothelioma, Lung cancer, Pemetrexed, Cisplatin
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.
Interventions
DRUGBAY 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)
DRUGPemetrexed
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
DRUGCisplatin
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
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability | Up to 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Italy, United States
Outcome results
None listed