Acimtamig Plus AlloNK Elicits Responses in Heavily Pretreated R/R Hodgkin Lymphoma

Acimtamig Plus AlloNK in R/R Hodgkin

Lymphoma | Image Credit: © Tatiana Shepeleva

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The addition of the innate cell engager acimtamig (AFM13) to AlloNK (AB-101) generated high objective and complete response (CR) rates in heavily pretreated patients with relapsed/refractory Hodgkin lymphoma who had exhausted standard-of-care treatment options, according to preliminary findings from the run-in portion of the phase 2 LuminICE-203 trial (NCT05883449).1

Early data presented at the 51st Annual EBMT Meeting demonstrated that at a data cutoff of November 14, 2024, among all 4 cohorts of patients with heavily pretreated relapsed/refractory Hodgkin lymphoma (n = 22), the objective response rate (ORR) was 86%, which included 12 complete responses (55%) and 12 partial responses. Responses were ongoing in 15 patients. The remaining 3 patients had progressive disease.

“Interestingly, [efficacy outcomes were] relatively similar across all of the cohorts, and most of these patients had continued responses,” lead study author Gunjan L. Shah, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, said in a presentation of the data.

Background, LuminICE-203 Design, and Patient Characteristics

In September 2023, the FDA granted fast track designation to acimtamig plus AlloNK for the treatment of patients with relapsed/refractory Hodgkin lymphoma.2

The open-label, multicenter, multicohort LuminICE-203 study included patients at least 18 years of age with relapsed/refractory Hodgkin lymphoma who had received at least 2 lines of prior treatment—including combination chemotherapy, brentuximab vedotin (Adcetris), and an immune checkpoint inhibitor.1 In the run-in portion of the study, patients were assigned to 1 of 4 cohorts to be treated with AlloNK at 3 x 2 billion cells (dose level 1) plus acimtamig at 200 mg (cohort 1; n = 6); dose level 1 of AlloNK plus acimtamig at 300 mg (cohort 2; n = 6); AlloNK at 4, 2, 2 billion cells (dose level 2) plus acimtamig at 200 mg (cohort 3; n = 6); or dose level 2 of AlloNK plus acimtamig at 300 mg (cohort 4; n = 6).

Standard lymphodepletion of intravenous (IV) fludarabine at 30 mg/m2 per day and IV cyclophosphamide at 300 mg/m2 was administered 3 to 5 days before day 1 of treatment. On days 1, 8, and 15, IV acimtamig, AlloNK, and 6 x 106 IU of subcutaneous interleukin-2 were co-administered. Acimtamig monotherapy was administered on days 22, 29, and 36 of a 58-day cycle for up to 3 cycles. Disease assessments per PET-CT were performed at screening, on day 43 of each cycle, and during follow-up.

The primary end point is ORR assessed by the Independent Radiology Committee (IRC) based on PET-CT and Lugano criteria. Secondary end points include duration of response and CR rate per investigator and IRC, progression-free survival per IRC, overall survival, safety, and pharmacokinetics.3

In the overall population, patients had a median age of 42.5 years (range, 23-80), and most patients were male (73%) and identified as White (91%).1 Of note, patients had ECOG performance statuses of 0 (36%) or 1 (64%). In total, 73% of patients had extranodal disease at screening. The median number of prior lines of therapy was 5 (range, 2-13), which included prior chemotherapy combination regimens (100%), prior brentuximab vedotin (100%), and prior checkpoint inhibitors (100%). Prior stem cell transplant or CAR T-cell therapy was received by 59% of patients, which consisted of autologous transplantation (55%), allogeneic transplantation (9%), and CAR T-cell therapy (5%).

Pharmacokinetics and Safety

In cohorts 1 and 2, the steady-state pharmacokinetics of acimtamig plus AlloNK were comparable with those of acimtamig monotherapy. The maximum serum concentration (Cmax)of free acimtamig was lower during the first infusion, which was consistent with a higher frequency of AlloNK. The mean CD16 receptor occupancy levels on CD56-positive and CD16-positive natural killer (NK) cells were similar between both cohorts.; these trends were similar to those observed with acimtamig monotherapy. Notably, increases in receptor occupancy levels were higher in both cohorts following the third treatment infusion, which was likely because of the higher Cmax of acimtamig that was reached after 3 doses.

Regarding safety, the combination of acimtamig and AlloNK was well manageable and was not associated with unexpected safety signals. There were no reported cases of graft-vs-host-disease or immune effector cell–associated neurotoxicity syndrome. All treatment-related adverse effects—including infusion-related reactions and cytokine release syndrome—were controlled with the treatment.

“These early results support the co-administration [of acimtamig and] this off-the-shelf, commercially scalable, allogeneic, cryopreserved NK cell product in a multicenter setting,” Shah concluded during the presentation. “Acimtamig with AlloNK may provide a safe and effective new therapeutic option for these patients who had had all of the other available treatments.”

Disclosures: Dr Shah reported receiving institutional research funding from Amgen, Beyond Spring, Bristol Myers Squibb, GPCR, Janssen, and Recordati; as well as serving as a member of a data safety monitoring board with ArcellX.

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References

1. Shah GL, Modi D, Feldman T, et al. Initial results of the LuminICE-203 study investigating acimtamig with off-the-shelf allogeneic natural killer cells (ALLONK) in relapsed or refractory classical Hodgkin lymphoma. Presented at: EBMT 51st Annual Meeting; March 30-April 2, 2025. Florence, Italy. Abstract GS2-2.
2. Affimed receives FDA fast track designation for AFM13 in combination with AlloNK for the treatment of patients with relapsed or refractory Hodgkin lymphoma. News release. Affimed. September 12, 2023. Accessed March 31, 2025. https://www.affimed.com/affimed-receives-fda-fast-track-designation-for-afm13-in-combination-with-allonk-for-the-treatment-of-patients-with-relapsed-or-refractory-hodgkin-lymphoma
3. Phase 2 study of AFM13 in combination with AB-101 in subjects with R/R HL and CD30+ PTCL (LuminICE-203). ClinicalTrials.gov. Updated November 13, 2024. Accessed March 31, 2025. https://clinicaltrials.gov/study/NCT05883449