The combination of Hu5F9-G4 (5F9) and rituximab was considered safe and produced durable complete responses (CRs) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) in a phase 1b trial.
Mainly low-grade adverse events (AEs) were observed with rituximab and 5F9, a macrophage-activating immune checkpoint inhibitor blocking CD47.
In addition, the combination produced an objective response rate (ORR) of 50% and a CR rate of 36%.
Most of the responses were ongoing at the time of data cutoff.
“It was very gratifying to see how the treatment was well-tolerated and showed a clinically meaningful response,” said Ranjana Advani, MD, of Stanford University in California.
She and her colleagues reported these results in The New England Journal of Medicine.
The study included 22 patients with relapsed or refractory NHL. Fifteen had diffuse large B-cell lymphoma (DLBCL), and seven had follicular lymphoma (FL).
The patients had received a median of four prior therapies (range, 2-10). Twenty-one patients had disease that was refractory to rituximab (all FL and 14 DLBCL patients).
All patients received 5F9 starting with a priming dose of 1 mg/kg followed by weekly maintenance doses of 10 to 30 mg/kg in three dose-escalation cohorts. The treatment was given until disease progression or lack of clinical benefit.
Patients received rituximab at 375 mg/m2 weekly starting on the second week of the first cycle and then monthly for cycles two through six.
The most common treatment-related AEs were chills (41%), headache (41%), anemia (41%), and infusion-related reactions (36%).
Serious AEs included infections (18%), anemia (4.5%), dyspnea (4.5%), pyrexia (4.5%), lactic acidosis (4.5%), retroperitoneal mass (4.5%), pulmonary embolism (4.5%), and infusion-related reaction (4.5%).
For the entire cohort, the ORR was 50% (n=11), and the CR rate was 36% (n=8).
Among DLBCL patients, the ORR was 40% (n=6), and the CR rate was 33% (n=5). In FL patients, the ORR was 71% (n=5), and the CR rate was 43% (n=3).
The median duration of response was not reached in either disease cohort. The median follow-up was 6.2 months for DLBCL and 8.1 months for FL.
Ten of 11 responders (91%) were still in response at the time of data cutoff.
The researchers said a phase 2 trial of 5F9 plus rituximab in relapsed or refractory B-cell NHL is ongoing.
The phase 1b study was supported by Forty Seven, Inc., and the Leukemia and Lymphoma Society. Dr. Advani reported disclosures related to Forty Seven, Inc., Bristol-Myers Squibb, Pharmacyclics, Seattle Genetics, and Roche/Genentech, among others.