FROM THE BRITISH JOURNAL OF CANCER
Bortezomib and KW-2478, a novel nonansamycin heat shock protein 90 (Hsp90) inhibitor, had modest activity and was well tolerated in an open-label phase 1/2 study of patients with relapsed or refractory multiple myeloma.
The objective response rate in 79 evaluable patients treated with the combination was 39.2%, and the clinical benefit rate was 51.9%. Median progression-free survival was 6.7 months, and median duration of response was 5.5 months, according to a report by Jamie Cavenagh, MD, of St. Bartholomew’s Hospital, West Smithfield, London, and colleagues. The results were published online in the British Journal of Cancer.
In the safety population of 95 patients, the most common treatment-related grade 3/4 adverse events were diarrhea, fatigue, and neutropenia, each occurring in 7.4% of patients, and nausea and thrombocytopenia, each occurring in 5.3% of patients (Br J Cancer. 2017 Sep 5. doi: 10.1038/bjc.2017.302).
KW-2478 showed synergistic antitumor activity with bortezomib in preclinical in vitro and in vivo studies, and the recommended phase 2 intravenous dosage of 175 mg/m2, along with 1.3 mg/m2 of bortezomib on days 1, 4, 8, and 11 of each 21-day cycle (up to eight cycles) in the current study was determined by phase 1 dose escalation; the maximum tolerated dose was not reached.
Although the antimyeloma activity of this novel treatment combination was relatively modest, the tolerability and apparent lack of overlapping toxicity suggest it deserves further exploration, including with alternate dosing schedules and combinations, for the treatment of relapsed/refractory multiple myeloma, the investigators concluded, noting that KW-2478 should also be studied in combination with other antimyeloma agents.
Kyowa Kirin Pharmaceutical Development Inc. funded the study. Dr. Cavenagh reported having no disclosures. Several other authors reported employment by the sponsor or by Kyowa Hakko Kirin Co. Ltd. Another, K. Yong, MD, reported receiving support from the National Institute for Health Research.