Efficacy Analysis From Phase I Study of Lorvotuzumab Mertansine (IMGN901), Used as Monotherapy, In Patients with Heavily Pre-Treated CD56-Positive Multiple Myeloma - A Preliminary Efficacy Analysis

Lorvotuzumab mertansine, also known as IMGN901 (huN901-DM1/BB-10901) is a novel anticancer agent consisting of a potent cytotoxic maytansinoid, DM1, attached to a CD56-binding monoclonal antibody, lorvotuzumab, using an engineered linker. Once bound to CD56 on a cancer cell and internalized, the DM1 is released to kill the cancer cell. Greater than 70% of multiple myeloma (MM) cases have surface expression of CD56. Safety information from the dose-escalation phase of this study was reported (ASH 114:2883, 2009) as the study was entering its expansion phase.

This study is designed to determine the MTD, pharmacokinetics (PK), and activity of IMGN901 used as monotherapy in patients with CD56+ MM, with additional information on its safety and efficacy to be obtained from its expansion phase.

Patients with CD56+ relapsed or relapsed/refractory MM receive a single IV infusion of IMGN901 weekly for 2 consecutive weeks every 3 weeks. During the dose-escalation phase, patients were enrolled into each dose level in cohorts of 3, with dose-limiting toxicity (DLT) triggering cohort expansion. Once the MTD was determined, an expansion cohort was opened to further characterize the safety and efficacy of IMGN901 administered at its MTD.

Thirty-seven CD56+ MM patients have received IMGN901 at doses ranging from 40 to 140 mg/m²/week with 19 patients treated at the MTD of 112 mg/m². Most of these 37 patients had been treated with 6 or more chemotherapy regimens prior to study entry. Among the 28 evaluable patients, 13 received IMGN901 treatment for more than three months, with 2 remaining on treatment for more than a year. Five of these patients achieved an objective response (OR) according to the European Bone Marrow Transplant Criteria – 2 partial responses and 3 minimal responses. The clinical benefit rate approximates 46%. Three patients have experienced four grade 3 drug-related toxicities that are considered at least possibly related to IMGN901: fatigue, renal failure, weakness, and absence of deep tendon reflexes. No grade 4 drug-related toxicities have been reported. No patients have demonstrated a humoral response against either the antibody or DM1 component of IMGN901.

In this population of patients with heavily pretreated MM, IMGN901 demonstrates an ability to provide sustained clinical benefit and tolerability. This warrants its continued investigation as monotherapy and supports its investigation as part of a combination regimen.

Jagannath:Millennium: Honoraria; Orthobiotec (Canada): Honoraria; Celgene: Honoraria; Merck: Honoraria; Onyx Pharma: Honoraria; Proteolix: Honoraria; Imedex: Membership on an entity's Board of Directors or advisory committees; Medicom World Wide: Membership on an entity's Board of Directors or advisory committees; Optum Health Education: Membership on an entity's Board of Directors or advisory committees; PER Group: Membership on an entity's Board of Directors or advisory committees. Zildjian:ImmunoGen, Inc.: Employment. O'Leary:ImmunoGen, Inc.: Employment.