Results of an ongoing Phase 1 clinical trial indicate that the anti-cancer drug lorvotuzumab mertansine in combination with Revlimid-dexamethasone is active in relapsed/refractory multiple myeloma patients.

“There is encouraging activity observed at all dose levels,” said Dr. Jesus Berdeja from the Sarah Cannon Research Institute in Nashville, Tennessee, who presented these findings at the 47^th Annual Meeting of the American Society of Clinical Oncology (ASCO) on Sunday.

In a summary talk about potential new myeloma treatments, Dr. Nikhil Munshi from the Dana-Farber Cancer Institute said that he was encouraged by these first results. He added that the combination’s response in Revlimid (lenalidomide)-refractory patients will tell whether the combination can overcome Revlimid resistance. He also indicated that future trials need to confirm whether lorvotuzumab mertansine and Revlimid act synergistically.

Lorvotuzumab mertansine (IMGN901), which is being developed by the U.S. biotech company ImmunoGen, is a chemotherapy agent (mertansine) attached to an antibody (lovortuzumab) that directs the chemotherapy to the cancer cell.  The lorvotuzumab portion of the drug recognizes the CD56 protein found on the surface of myeloma cells. Approximately 70 percent of myeloma patients have myeloma cells with the CD56 protein.

A prior Phase 1 study showed that lorvotuzumab mertansine is safe and effective for relapsed/refractory myeloma patients when taken by itself. Preclinical studies have also indicated that lorvotuzumab mertansine shows enhanced anti-cancer activity when used in combination with Revlimid and dexamethasone (Decadron).

In this study, the study authors sought to determine the effectiveness of lorvotuzumab mertansine in combination with Revlimid-dexamethasone for relapsed/refractory myeloma patients with CD56 on their myeloma cells. They also observed the drug’s side effects and maximum tolerated dose.

Lorvotuzumab mertansine was administered intravenously at escalating doses (75 mg/m², 90 mg/m², and 112 mg/m²) once per week for three weeks in a four-week treatment cycle. In addition, all patients received 25 mg Revlimid orally on days 1 to 21 as well as 40 mg dexamethasone orally once per week. Patients were treated until disease progression or the development of unacceptable side effects.

Dr. Berdeja reported that 16 patients have enrolled in the study to date. The median age of the patients was 60 years, and the majority of patients had received more than three prior therapies. Nine patients (56 percent) had received prior Revlimid therapy.

Dr. Berdeja reported that 13 patients are currently evaluable for response and that so far the overall response rate has been 62 percent.  Specifically, 39 percent achieved a very good response and 23 percent achieved a partial response. Dr. Berdeja also mentioned that patients with unfavorable chromosomal abnormalities, such as mutations in chromosomes 13, 14, or 17, responded to treatment.

He added that responses were seen at all dose levels. However, Dr. Berdeja said that most patients had to be dose-reduced. “All of the dose reductions were done for peripheral neuropathy [nerve damage to the extremities],” he explained.

“Interestingly, many of these patients continued to respond on the lower dose, and most of them also improved their peripheral neuropathy after dose reduction,” he added.

Based on these findings, more participants have been enrolled at the 75 mg/m² dose level. “There have been no dose reductions required at this dose level,” said Dr. Berdeja.

According to Dr. Berdeja, the treatment was well-tolerated. “We did not observe any life-threatening side effects, and severe side effects were minimal,” he explained.

The majority of severe side effects were peripheral neuropathies.

The study authors are currently recruiting additional patients for the 75 mg/m² lorvotuzumab mertansine arm of the study with the goal of having a total of 52 patients participate in the study.

For more information, see abstract 8013 on the ASCO meeting website.