Timdarpacept (IMM01) in combination with tislelizumab in prior anti-PD-1 failed classical Hodgkin lymphoma: An open label, multicenter, phase II study (IMM01-04) evaluating safety as well as preliminary anti-tumor activity.

7017 Background: Timdarpacept (IMM01), a recombinant SIRPa-Fc fusion protein, can activate macrophages to enhance anti-tumor activity by blocking CD47-SIRPa interaction. IMM01 showed unique property of weak human erythrocyte conjugation in preclinical studies, and low incidence of anemia in early clinical trials with no need for a priming dose. IMM01 in combination with tislelizumab has the potential to augment both innate and adaptive anti-tumor immune responses. Methods: Eligible patients with R/R classical Hodgkin lymphoma (cHL) who have failed prior anti-PD-1 treatment were enrolled in this open-label, multicenter phase II study (NCT05833984). IMM01 (2.0mg/kg) intravenously administered each week in each 3-week treatment cycle, while tislelizumab (200mg) will be administered once every 3 weeks until disease progression or intolerable toxicity. Objective response rate (ORR) by Lugano 2014 was the primary endpoint and secondary endpoints include tolerability, disease control rate (DCR), duration of response (DoR), progression free survival (PFS) and time to response (TTR). Results: As of 28 Dec 2023, 33 cHL patients were enrolled. The median age was 35 years (range 19-77) with 23 (69.7%) male patients. The median prior lines of therapy were 4. In efficacy evaluable patients (n=32) with median follow up of 5.65 month (95% CI, 2.83-6.90), the ORR was 65.6% (21/32), complete response rate was 18.8% (6/32) and DCR was 93.8% (30/32). The DoR rate at 3 months, 6 months were 92.9% and 60.8%, respectively. The mDoR was not reached. The PFS rate at 3 months, 6 months were 84.5% and 68.7%, respectively. Median TTR was 1.6 months. Further analysis indicated that regardless of primary or secondary resistance to tislelizumab treatment, other PD-1-containing regimens (non-tislelizumab), or prior CD30-ADC treatment; or the intervals from last dose of prior PD-1 treatment to first dose of IMM01 and tislelizumab, patients can benefit from IMM01 combined with tislelizumab treatment. All patients experienced at least one treatment-related adverse events (TRAEs). The most common TRAEs were WBC decreased (48.5%), PLT decreased (42.4%), anemia (36.4%), ANC decreased (33.3%), lymphocyte decreased (30.3%). TRAEs of grade ≥3 occurred in 15 (45.5%) patients, with the most common being lymphocyte decreased (30.3%), WBC decreased (12.1%), PLT decreased (12.1%), ANC decreased (12.1%). There was no reported hemolytic anemia or hemolysis in any of the patients. 4 (12.1%) patients had treatment related SAE. No patients experienced TRAEs leading to the study drug discontinuation or death. Conclusions: IMM01-04 showed a robust anti-tumor effectivity with a well-tolerated safety profile in prior anti-PD-1 failed cHL patients. The phase II study is ongoing. Clinical trial information: NCT05833984 .