Updated efficacy and safety results from the phase 2 study of timdarpacept in combination with tislelizumab in patients with classical Hodgkin lymphoma for whom prior anti–PD-1 therapy failed.

Abstract

7041 Background: Timdarpacept (IMM01), a recombinant SIRPa-Fc fusion protein, can activate macrophages to enhance anti-tumor activity by blocking CD47-SIRPa interaction. Timdarpacept showed unique property of weak human erythrocyte binding in preclinical studies, and low incidence of anemia in early clinical trials with no need for a priming dose. Methods: Eligible patients (pts) with R/R classical Hodgkin lymphoma (cHL) who had failed prior anti-PD-1 treatment were enrolled in this study (NCT05833984). Timdarpacept (2.0mg/kg, QW) and tislelizumab (200mg, Q3W) were intravenously administered in 3-week treatment cycle 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 18 Oct 2024, 33 cHL pts were enrolled with 19 refractory to anti PD-(L) 1 therapy (best objective response was SD/PD or CR/PR and progressed within 12 weeks of last dose). The median age was 35 years with 23 (69.7%) male pts. The median prior lines of therapy were 4. In all 33 efficacy-evaluable pts with median follow up of 13.83 months, the ORR, complete response (CR) rate and DCR were 69.7%, 24.2% and 93.9%, respectively. For PD-(L) 1 refractory pts, the ORR was 68.4%, and 1 pt achieved CR. The median TTR was 1.6 months. The median DoR was not reached. Further analysis indicated that pts could benefit from timdarpacept combined with tislelizumab treatment regardless of being relapsed or refractory to anti-PD-1 treatment, or having had prior CD30-ADC treatment or not. All pts experienced treatment-related adverse events (TRAEs), 17 (48.5%) of whom experienced grade 3/4 TRAE. The most common TRAEs were WBC decreased (57.6%), PLT decreased (42.4%), anemia (39.4%), ANC decreased (39.4%), lymphocyte decreased (30.3%). Six (18.2%) pts had treatment related SAE. Three pts (9.1%) had an IMM01 dose reduction. One pt (3.0%) experienced permanent discontinuation of IMM01. No TRAEs led to death. Conclusions: Timdarpacept in combination with tislelizumab showed promising therapeutic efficacy and a well-tolerated safety profile in cHL patients for whom anti-PD-1 failed, providing evidence for future investigation. Clinical trial information: NCT05833984 .