Results from the completed dose-finding part of phase 2 study of the innate cell engager acimtamig (AFM13) in combination with AlloNK (AB-101) in relapsed or refractory classical Hodgkin lymphoma (LuminICE-203).

Abstract

7008 Background: There is an unmet need for new treatment approaches for patients (pts) with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) who progress following standard systemic therapies. Combining acimtamig (AFM13), a tetravalent bispecific CD30/CD16A innate cell engager (ICE), with AlloNK (AB-101), a cryopreserved, off-the-shelf, cord blood-derived NK cell product, induces antibody-dependent cellular cytotoxicity against CD30+ lymphoma cells. Methods: This Phase 2, open-label, multi-center, multi-cohort study (LuminICE-203; NCT05883449) is evaluating the efficacy and safety of acimtamig in combination with AlloNK in pts with R/R HL. An initial dose-finding part with 4 cohorts is investigating 2 doses of acimtamig (200 mg or 300 mg weekly flat dosing for 6 weeks) in combination with AlloNK (dose level 1 [DL1]: 3 doses of 2×10 9 cells on Days 1, 8 and 15; or dose level 2 [DL2]: 1 dose of 4×10 9 on Day 1, followed by 2 doses of 2×10 9 cells on Days 8 and 15), after a standard lymphodepletion up to 3 cycles, followed by a randomized part using a Simon’s 2-stage design. The primary endpoint is objective response rate (ORR) assessed by an Independent Radiology Committee (IRC) based on PET-CT per Lugano classification criteria. Results: As of 16 December 2024, 24 pts with R/R HL were treated in the initial dose-finding part of the study and were assessed by the IRC for metabolic response. Median (range) age was 42.5 (23–80) years; 16 (67%) were male. All pts in the study were heavily pretreated with chemotherapy, brentuximab vedotin and PD-1 inhibitors; median (range) prior treatment lines was 4.5 (2–13), including previous stem cell transplant in 14 (58%) pts. An ORR of 88% was achieved with 14 (58%) complete responses (CR) (Table). The safety profile was in line with that previously reported, with mostly mild to moderate infusion related reactions as the most common reported treatment-related adverse event (TRAE) in 50% of patients; no fatal TRAEs and no stopping criteria have been observed. The study is ongoing and updated safety and efficacy results, including pharmacokinetic / pharmacodynamic analyses and preliminary results on duration of response will be presented. Conclusions: Acimtamig in combination with AlloNK shows promising efficacy with a well-managed safety profile with the potential to address an unmet need in pts with R/R HL who have exhausted standard-of-care treatment options. Clinical trial information: NCT05883449 . Efficacy results of acimtamig plus AlloNK in pts with R/R HL. Efficacy, n (%)(Best Response per Lugano Criteria) AlloNK DL1+ 200 mg acimtamig(N=6) AlloNK DL1+ 300 mg acimtamig(N=6) AlloNK DL2+ 200 mg acimtamig(N=6) AlloNK DL2+ 300 mg acimtamig(N=6) Totaldose-finding part(N=24) CR 4 (67) 3 (50) 4 (67) 3 (50) 14 (58) ORR 5 (83) 5 (83) 6 (100) 5 (83) 21 (88)