Preliminary Safety and Efficacy Evaluation of IMM0306, a CD47 and CD20 Bispecific Monoclonal Antibody-Trap (mAb-Trap), from an Ongoing Phase I Dose-Escalation Study in Patients with Relapsed or Refractory B-Cell Non- Hodgkin's Lymphoma (R/R B-NHL)

Abstract

Background: IMM0306, a recombinant bispecific mAb-Trap targeting CD20 and CD47, has higher affinity for CD20 than for CD47, thus enabling its preferential and simultaneous binding to CD20 and CD47 on malignant B cells rather than to CD47-postive normal tissues. Here, we present preliminary safety and efficacy data from an ongoing dose-escalation study in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL) (CTR20192612). Methods: IMM0306-I is a first-in-human, phase I dose escalation and dose expansion study of IMM0306. 7 dose levels (0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6 mg/kg) were to be evaluated in the dose escalation phase of the study following a modified 3+3 escalation schema. After single-dose period (2 weeks), IMM0306 was administered intravenously once per week (QW) until disease progression or intolerable toxicity. Dose-limiting toxicity (DLT) was evaluated in the 28 days post the initial 2-week single dose period. Safety was evaluated per CTCAE 5.0; tumor assessments performed once every 8 weeks, and pharmacokinetics (PK) assessed after single and multiple doses of IMM0306 administration. Results: As of Jul 13th, 2022, 26 patients were treated with seven dose levels of IMM0306. 10 (39%) pts received 3 or more prior lines of therapy; all pts received prior anti-CD20 therapy. No DLTs have been observed by the date of data cut-off and the maximum tolerated dose (MTD) not reached. IMM0306 was generally well tolerated. The most frequent (>20%) treatment-related adverse events (TRAEs) were lymphocyte decrease (65.4%), White Blood Cell (WBC) decrease (61.5%), neutropenia (50.0%), anemia (50.0%), infusion- related reactions (IRR) (38.5%), platelet (PLT) count decrease (30.8%), most of them are Grade1-2. The most common G3 or above TRAE were lymphocyte decrease (65.4%), WBC decrease (23.1%), absolute neutrophil count (ANC) decrease (15.4%), anemia (11.5%), PLT count decrease (7.7%), respectively. Two treatment related SAE patients are G4 PLT decrease and chest pain respectively. These two patients discontinued the study treatment after the event resolved (note: this subject reported G4 PLT decrease at the dose of 1.6 mg/kg at C1D30). Among total 23 evaluable patients, one follicular lymphoma patient achieved complete response (CR) at the dose level of 1.2 mg/kg. 2 partial response (PR) at 0.8 and 1.2 mg/kg dose level (one is for marginal zone lymphoma, the other is for follicular lymphoma) respectively. Six patients reached stable disease (SD). PK data has yet to be collected. Conclusions: These data indicate that IMM0306 is well-tolerated at the dose levels evaluated. and preliminary anti-tumor efficacy result observed support continuous development of IMM0306 in patients with R/R B-NHL. The phase 1/2 is ongoing.