acimtamig (AFM13)

The bispecific innate cell engager acimtamig (AFM13) was superior to IgG1 monoclonal antibodies in ADCC and in increasing the fraction of cytotoxic NK cells and serial killers...These results demonstrate that CD16A shedding represents an intrinsic feature of NK cell biology that is critical to sustain the antitumoral cytotoxicity of NK cells. This has implications for CD16A engineering of NK cell products and their combination with CD16A-directed NK cell engagers.

P1/2, N=45, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | N=30 --> 45 | Trial completion date: Apr 2027 --> Sep 2025 | Trial primary completion date: Apr 2027 --> Sep 2025

P2, N=25, Terminated, Affimed GmbH | N=154 --> 25 | Trial completion date: Nov 2027 --> Jun 2025 | Recruiting --> Terminated | Trial primary completion date: Apr 2026 --> Nov 2024; Due to sponsor decision

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2025 --> Apr 2027 | Trial primary completion date: Apr 2025 --> Apr 2027

Outcomes of patients with CD30-positive (CD30+) lymphomas have improved with the advent of brentuximab vedotin (BV) and, in Hodgkin lymphoma, anti-PD1 checkpoint inhibitors (CPI)...AFM13-a CD30/CD16A bispecific antibody-activates natural killer (NK) cells to kill CD30+ cells...This therapy showed encouraging preliminary safety and efficacy. ClinicalTrials.gov Identifier: NCT04074746 .

The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30+ lymphomas continues in combination with allogeneic natural killer cells.

P2, N=108, Completed, Affimed GmbH | Active, not recruiting --> Completed

Targeted therapies, including the antibody drug conjugate, camidanlumab tesirine, and transcriptional agents such mammalian target of rapamycin and histone deacetylase inhibitors have shown some potential in patients with refractory disease. Clinical trials with cellular therapies, including chimeric antigen receptor T cells targeting CD30 and allogeneic natural killer cells combined with AFM13, a CD30/CD16a-bispecific antibody, have shown promising results. The availability of more therapeutic options for this patient population is eagerly awaited.

AB-101 has demonstrated potent killing of tumor cell lines in vitro and in vivo, and preliminary results of a Phase 1/2 trial of AB-101 alone and in combination with rituximab in patients with R/R B cell non-Hodgkin lymphoma demonstrated AB-101 is well tolerated (Khanal et al...Patients aged ≥18 years are planned for enrolment and patients with R/R HL must have received at least two prior lines of therapy including prior combination chemotherapy, brentuximab vedotin (BV) and a checkpoint inhibitor...A run-in phase will assess two dose levels of AFM13 and AB-101 in 4 cohorts (Figure). A standard lymphodepletion regimen of fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day) will be administered IV from Day −5 to Day −3 at the start of each treatment cycle...In addition, an exploratory cohort (cohort 5) will begin enrolment of patients with CD30+ PTCL. Disease and efficacy assessments will be conducted at screening and on Day 43 (± 3 days) of each cycle.

Pts ages 15–75 with CD30+ lymphomas refractory to brentuximab vedotin were enrolled...Each treatment cycle consisted of fludarabine/cyclophosphamide (days −5 to −3) followed by infusion (day 0) of the AFM13-precomplexed CB NK cells, cultured for 14 days as described above, and three weekly IV infusions of AFM13 (200 mg, days 7, 14 and 21)... CB-derived cytokine-induced memory-like NK cells precomplexed with AFM13 have excellent tolerability and activity for pts with heavily pretreated and refractory CD30+ lymphoma.

P2, N=154, Recruiting, Affimed GmbH | Not yet recruiting --> Recruiting

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Apr 2024 --> Apr 2025