S867 THE FIRST‐IN‐CLASS ANTI‐CD47 ANTIBODY HU5F9‐G4 WITH RITUXIMAB INDUCES DURABLE RESPONSES IN RELAPSED/REFRACTORY DLBCL AND INDOLENT LYMPHOMA: INTERIM PHASE 1B/2 RESULTS

• Published in: HemaSphere 2019-06, Vol.3 (S1), p.388-n/a
• Main Authors: Advani, R., Bartlett, N., Smith, S., Roschewski, M., Popplewell, L., Flinn, I., Collins, G., Ghosh, N., LaCasce, A., Asch, A., Kline, J., Kesavan, M., Tran, T., Lynn, J., Huang, J., Agoram, B., Volkmer, J.‐P., Takimoto, C., Chao, M., Mehta, A.
• Format: Article
• Language: English
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/01.HS9.0000561748.38640.dd

Background: Hu5F9‐G4 (5F9) is a first‐in‐class IgG4 antibody targeting CD47, a macrophage immune checkpoint and “don’t eat me” signal on cancers leading to phagocytosis of tumor cells. Pre‐clinically, 5F9 synergizes with rituximab to eliminate lymphoma by enhancing antibody‐dependent cellular phagocytosis. 5F9+rituximab demonstrated encouraging safety/efficacy in a Phase (Ph)1b dose escalation cohort in patients with relapsed/refractory (r/r) DLBCL and FL that were rituximab‐refractory (Advani et al., NEJM 2018). Herein we report on extended follow up of this Ph1b cohort and preliminary Ph2 data. Aims: The primary objectives were to determine the safety/efficacy of escalating doses of 5F9+rituximab in patients with r/r DLBCL and indolent lymphoma. Methods: The Ph2 enrolled: 1) DLBCL: primary refractory or r/r to at least 2 prior therapies, ineligible for CAR‐T therapy; and 2) indolent lymphoma (FL and MZL) r/r to at least 2 prior therapies. A 5F9 prime/maintenance dose regimen was used to mitigate on‐target anemia; followed by weekly or Q2 week maintenance doses. Based on a potential dose‐response seen in Ph1b, 5F9 maintenance doses of 30 and 45 mg/kg were tested with rituximab. Results: A total of 100 patients (63 DLBCL, 35 FL, 2 MZL) have been treated across both Ph1b+2 cohorts. Median age (range) was 66 years (21–88) with 3 median prior therapies (range 1–10). 84% were rituximab‐refractory and 72% refractory to their last therapy. 5F9+rituximab was well‐tolerated at 5F9 doses up to 45 mg/kg with no maximum tolerated dose reached. No significant dose‐dependent toxicities were observed. Treatment‐related AEs occurring in >10% of patients included infusion reactions (38%), headache (34%), chills (30%), fatigue (30%), anemia (27%), nausea (24%), pyrexia (23%) vomiting (13%), and back pain (11%). The majority were G1/2 with 7% or lower being G3/4, except G3 anemia (15%) which was an expected transient first‐dose effect. Treatment discontinuation due to drug‐related AEs occurred in only 4/100 (4%) patients. As of February 2019, for Ph1b patients dosed from 10–30 mg/kg (n = 22), at a median follow up of 12 months (DLBCL) and 18 months (FL), the median duration of response had not been reached (DLBCL range: 2.4 – 20+ months and FL range: 6.2 – 22.6+ months), including some durable CRs for > 20 months. Of 100 total patients enrolled, 75 patients were evaluable for efficacy, 8 were not evaluable, and in 17 first response assessment is pending. Pooled efficacy res