phase ib study of anetumab ravtansine in combination with pemetrexed and cisplatin in mesothelin-expressing solid tumors

Conditions: Medical Oncology

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.

Keywords: phase 1 solid tumors mesothelioma lung cancer pemetrexed cisplatin