©ASCO/Rodney White
CHICAGO—A 3-drug combination is safe and highly active in certain patients with relapsed B-cell malignancies, according to a speaker at the 2015 ASCO Annual Meeting.
The combination consists of the anti-CD20 monoclonal antibody ublituximab, the PI3Kδ inhibitor TGR-1202, and the BTK inhibitor ibrutinib.
In a small, phase 1 study, the triplet produced an overall response rate of 62%. It was particularly active in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and those with mantle cell lymphoma (MCL).
The most common adverse events were infusion reactions, gastrointestinal events, rash, and fatigue. Grade 3 neutropenia and leukopenia occurred in 1 patient each.
Nathan Fowler, MD, of MD Anderson Cancer Center in Houston, Texas, presented these results at the meeting as abstract 8501.*
The trial enrolled 16 patients with CLL/SLL or non-Hodgkin lymphoma (NHL). Four had CLL, 1 had SLL, and 1 had Richter’s transformation. Four patients had follicular lymphoma (FL), 3 had diffuse large B-cell lymphoma (DLBCL), 2 had mantle cell lymphoma (MCL), and 1 had marginal zone lymphoma (MZL).
The patients’ median age was 63, and their median number of prior treatment regimens was 4 (range, 1-5). Fifty percent of patients (n=8) were refractory to prior therapy.
Treatment consisted of 900 mg of ublituximab, ibrutinib at either 420 mg (CLL/SLL) or 560 mg (NHL), and TGR-1202 at 3 different doses: 400 mg, 600 mg, or 800 mg. Ibrutinib and TGR-1202 were given once-daily beginning on day 1 of each cycle. Ublituximab was given on days 1, 8, and 15 of cycles 1 and 2, then on day 1 of cycles 4, 6, 9, and 12.
Safety and efficacy
Sixteen patients were evaluable for safety and 13 for efficacy. One of the patients was removed from the efficacy analysis at the discretion of the investigators, and it was too early to evaluate the other 2 patients.
The median time on study was 4 months (range, 1-9 months). The 5 CLL/SLL patients received TGR-1202 at 400 mg. One of these patients had a dose-limiting toxicity—reactivation of varicella zoster.
Of the NHL patients, 3 received TGR-1202 at 400 mg, 4 received 600 mg, and 4 received 800 mg. There were no dose-limiting toxicities in any of these patients.
Adverse events that were considered possibly related to treatment included infusion reactions (25%), diarrhea (19%), nausea (19%), fatigue (19%), rash (19%), anemia (13%), neutropenia (13%), leukopenia (13%), and insomnia (13%). Grade 3 events included neutropenia and leukopenia (6% each), and there were no grade 4 events.
“The majority of patients have demonstrated a response to the therapy,” Dr Fowler said. “All of the patients that have responded continue on treatment, and the longest [treatment duration] is about 10 months.”
The only complete response occurred in a patient with MCL. Partial responses occurred in all 3 CLL patients, 2 FL patients, the SLL patient, the MZL patient, and 1 MCL patient. One patient with FL, 2 with DLBCL, and 1 with Richter’s transformation did not respond to treatment.
In closing, Dr Fowler said this treatment was well-tolerated and showed significant early activity in this heavily pretreated patient population. Dose-escalation with TGR-1202 continues at 800 mg, and phase 2 studies of the triplet are planned.
*Information in the abstract differs from that presented at the meeting.