AlloNK Plus Rituximab Induces Durable Responses in R/R B-Cell NHL

R/R Non-Hodgkin Lymphoma | Image Credit:
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The combination of AlloNK (AB-101) plus rituximab (Rituxan) produced high complete response (CR) rates and prolonged responses beyond 12 months in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-cell NHL), according to updated data from a phase 1/2 trial(NCT04673617) presented at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting.1

Among patients who received AlloNK plus rituximab and were naive to prior CAR T-cell therapy (n = 14), the CR rate was 64%. These patients had received a median of 3 prior lines of therapy, and 13 had aggressive B-cell NHL. As of the March 7, 2025, data cutoff, the median duration of response (DOR) had not yet been reached, with responses lasting at least 19.4 months. CRs were sustained in the majority of treated patients.

According to the drug’s developer, Artiva Biosciences, these CR rates and durability outcomes are comparable with those seen in registrational trials of approved autologous CAR-T cell therapies in similar heavily pretreated populations with aggressive B-cell NHL. For example, treatment with axicabtagene ciloleucel (axi-cel; Yescarta) in the phase 1 ZUMA-1 trial (NCT02348216) produced a CR rate of 58% and median DOR of 11.1 months; lisocabtagene maraleucel (liso-cel; Breyanzi) generated a CR rate of 53% and median DOR of 23.1 months in the phase 1 TRANSCEND NHL 001 trial (NCT02631044); and tisagenlecleucel (Kymriah) yielded a CR rate 40% and median DOR that was not yet reached at 40.3 months of follow-up in the phase 2 JULIET trial (NCT02445248).

“We are thrilled to see continuing durability, now with an ongoing median DOR of at least 19 months. These data are maturing as one of the data sets with the highest activity and durability for any allogeneic cell therapy in heavily pretreated [patients with] aggressive B-cell NHL and in line with approved autologous CAR T[-cell] therapies,” Fred Aslan, MD, CEO of Artiva, stated in a news release. “AlloNK has now demonstrated its ability to significantly enhance the activity of both anti-CD20 rituximab and Affimed’s CD30-directed NK cell engager AFM13 in later-line cancer populations. These findings reinforce the potential of AlloNK to drive deep and durable responses in autoimmune diseases through the enhancement of standard-of-care monoclonal antibodies and robust B-cell depletion.”

The first-in-human, multicenter, United States–based phase 1/2 trial is assessing the efficacy and safety of outpatient administration of AlloNK, a genetically modified, cord blood–derived, allogeneic, cryopreserved natural killer cell therapy that has been optimized for use alongside monoclonal antibody therapy.2 Eligible patients must have relapsed/refractory CD20-positive B-cell malignancies; have received 2 or more prior lines of therapy; have an ECOG performance status of 0 or 1; and have no prior allo TX or central nervous system involvement. Prior receipt of CAR T-cell therapy is allowed.

Upon enrollment, patients will receive either AlloNK as monotherapy or in combination with the anti-CD20 antibody rituximab. All eligible patients will undergo lymphodepletion from days -5 to -3 of cycles 1 and 2, comprising 250 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine. After conditioning chemotherapy, AlloNK will be delivered in 4 weekly doses of either 1 billion or 4 billion cells per dose, each with IL-2 cytokine support.

For patients in the combination arm, 3 doses of rituximab at 375 mg/m² will also be administered during cycles 1 and 2, followed by 2 doses in cycles 3 and 4. The monotherapy arm is limited to 1 cycle of AlloNK, while up to 4 treatment cycles are permitted in the combination therapy arm in the absence of toxicity or disease progression.

The study’s end points include safety and tolerability, antitumor activity, and pharmacokinetics.

Initial results from the dose-escalation stage of the ongoing phase 1/2 study, which were previously presented at the 2023 ASCO Annual Meeting, demonstrated an objective response rate of 57.1% among efficacy-evaluable patients who received 1 billion cells per dose of AB-101 plus rituximab (n = 7). This included 3 CRs and 1 partial response. Moreover, at the data cutoff, 3 patients had ongoing responses and were progression free for 5+, 7+, and 9+ months.​ The agent was well tolerated at the 1 billion and 4 billion cells per dose levels and was successfully administered for up to 16 consecutive doses in an outpatient setting.

Updated results have corroborated these findings, deeming the safety profile of AlloNK plus rituximab to be favorable among all 45 patients treated.1 All reported cytokine release syndrome (CRS) events were reclassified as infusion-related reactions (IRRs) based on cytokine profiling of the 3 patients with low-grade CRS, which showed no elevation in IL-6 or other inflammatory cytokines. Additionally, these events all occurred within 24 hours of infusion and were resolved without the need for intervention, further supporting this reclassification. No cases of immune effector cell-associated neurotoxicity syndrome, graft-vs-host disease, or deaths related to AlloNK were reported, and there were no trial discontinuations due to AlloNK-related adverse effects (AEs).

Consistent with lymphodepletion-based regimens, the most common treatment-emergent AEs (TEAEs) were hematologic, including neutropenia (84%), leukopenia (82%), and lymphopenia (71%). Serious TEAEs reported in more than 1 patient included IRRs and febrile neutropenia (7% each).

Based on these findings, Artiva Biosciences asserted that AlloNK induces potent and durable B-cell depletion in a heavily pretreated relapsed/refractory population. Moreover, the regimen’s safety profile supports its potential for outpatient administration, including in older patients with aggressive disease.

“I had the opportunity to dose the first patient with rituximab in 1997 and have most recently adopted the clinical use of autologous CAR T-cell therapies,” David G. Maloney, MD, PhD, professor emeritus of Translational Science and Therapeutics at the Fred Hutch Cancer Center, added in the news release. “It is encouraging to see AlloNK demonstrate robust responses and meaningful durability in tough-to-treat later-line patients with aggressive NHL that are comparable to those with autologous CAR T-cell therapies. The available B-NHL data of AlloNK in combination with rituximab supports readthrough of AlloNK’s mechanism of action from treatment of aggressive B-NHL to treatment of autoimmune diseases.”

References

1. Artiva Biotherapeutics announces longer-term phase 1/2 data demonstrating prolonged durability for AlloNK® in combination with rituximab in patients with B-cell-non-Hodgkin Lymphoma at the ASGCT 28th Annual Meeting. News release. Artiva Biosciences. May 13, 2025. Accessed May 14, 2025. https://investors.artivabio.com/News-and-Events/news/news-details/2025/Artiva-Biotherapeutics-Announces-Longer-term-Phase-12-Data-Demonstrating-Prolonged-Durability-for-AlloNK-in-Combination-with-Rituximab-in-Patients-with-B-cell-Non-Hodgkin-Lymphoma-at-the-ASGCT-28th-Annual-Meeting/default.aspx
2. Khanal R, Mehta A, Maly J, et al. AB-101, an allogeneic, non–genetically modified, natural killer (NK) cell therapy, evaluated as monotherapy or in combination with rituximab in R/R non-Hodgkin lymphoma. J Clin Oncol. 2023;41(suppl 16):752. doi:10.1200/JCO.2023.41.16_suppl.7529