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Efficacy results from a phase I study of lorvotuzumab mertansine (IMGN901) in patients with CD56-positive solid tumors.
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2011
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Surgical OncologyCancer ManagementImmunologyPathologyTumor BiologyEfficacy ResultsOvarian CancerOncologyMetronomic TherapyRadiation OncologyMolecular OncologyE13582 BackgroundCancer ResearchLorvotuzumab MertansineCd56-positive Solid TumorsCancer TreatmentLung CancerImmune Checkpoint InhibitorMerkel Cell CarcinomaMedicine
e13582 Background: Lorvotuzumab mertansine is a conjugate of the cytotoxic maytansinoid, DM1, and the CD56-binding antibody, lorvotuzumab, and is designed to bind to and kill CD56-expressing cancer cells. Approximately 55-60% of ovarian cancer (OC) and virtually all small-cell lung cancer (SCLC) and Merkel cell carcinoma (MCC) tumors express CD56. After establishing the MTD of lorvotuzumab mertansine in a dose-finding phase, patient enrollment was initiated in an expansion phase to assess the compound in patients with OC, SCLC, or MCC. While assessment in MCC and SCLC has been ongoing, patients with OC only recently began to enter the study. Methods: The expansion phase is open to patients with relapsed or refractory SCLC who have received only one prior therapy and to patients with MCC or OC who have received at least one prior therapy. Patients must meet standard eligibility criteria. However, patients with neurological toxicity ≥ grade 2 or recent history of pancreatitis are excluded. Approximately 100 patients are planned for accrual, with response assessed according to RECIST criteria. In addition, PK and pharmacodynamics correlative studies are being conducted. Lorvotuzumab mertansine is administered intravenously for 3 consecutive days every 21 days at the recommended phase II dose of 60 mg/m2/day. Results: Eighty-five patients have been enrolled in this study with 33 (9-SCLC, 14-MCC, 7-OC, 3-Other) patients treated in the expansion cohort. Objective responses were observed in three patients (1 CR in MCC, 1 clinical CR in MCC, 1 unconfirmed PR in SCLC). Protocol-defined SD was seen in 18 patients with a subset of 15 patients experiencing clinically relevant TTP (≥75 days). Updated efficacy and safety data for all patients will be reported, including the first experience with the compound in OC. Conclusions: Lorvotuzumab mertansine has shown preliminary evidence of meaningful clinical activity with an acceptable safety profile, with experience in OC now being gained.