ATLANTA—A 2-drug combination has produced a high response rate in a small trial of patients with relapsed/refractory (R/R), Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).
The combination, inotuzumab ozogamicin and bosutinib, produced an overall response rate of 81% in this ongoing, phase 1/2 trial.
Nitin Jain, MD, of the University of Texas MD Anderson Cancer Center in Houston, presented phase 1 results from the study at the 2017 ASH Annual Meeting (abstract 143*).
He reported results in 16 patients, 14 with R/R, Ph+ ALL and 2 with chronic myeloid leukemia in lymphoid blast phase.
The patients received inotuzumab ozogamicin at 0.8 mg/m2 on day 1, 0.5 mg/m2 on day 8, and 0.5 mg/m2 on day 15 of cycle 1. Patients who achieved a response received inotuzumab ozogamicin at 1 mg/m2 once every 4 weeks for subsequent cycles. Six cycles were planned.
Patients also received bosutinib at 300 mg, 400 mg, or 500 mg once a day for 4-week cycles. The median number of cycles was 2.5 (range, 1-8).
The maximum-tolerated dose has not been established, but there were 2 dose-limiting toxicities (DLTs). One DLT occurred with the 400 mg dose of bosutinib, and 1 occurred with the 500 mg dose. Both DLTs were grade 3 skin rash.
The investigators are continuing accrual with the 500 mg dose of bosutinib for the phase 2 portion of the trial, with 22 additional patients.
Response and survival
The overall response rate was 81% (n=13). This included a complete response (CR) in 8 patients, a CR with incomplete blood count recovery in 3 patients, and a CR with incomplete platelet recovery in 2 patients.
All responses occurred among the patients with ALL.
Twelve responders achieved complete cytogenetic remission, 11 achieved a major molecular response, 8 achieved a complete molecular response, and 9 were negative by flow cytometry.
The median duration of response was 8.8 months.
Of the 13 responders, 6 went on to receive an allogeneic stem cell transplant. Five of these patients are still alive, but 1 died from relapse.
The median overall survival was 10.7 months.
“These data suggest the tolerability and efficacy of inotuzumab ozogamicin and bosutinib in R/R Ph+ ALL,” Dr Jain said. “And we are looking forward to the next phase of this study.”
Dr Jain disclosed receiving research funding from Celgene, Verastem, BMS, Incyte, Pharmacyclics, ADC Therapeutics, Genentech, AbbVie, Pfizer, Astra Zeneca, Janssen, Cellectis, and Seattle Genetics. He disclosed membership on boards of directors/advisory committees for Verastem, Servier, Novimmune, Pharmacyclics, Novartis, ADC Therapeutics, AbbVie, Pfizer, Adaptive Biotechnologies, and Janssen.
*Data in the presentation differ from the abstract.