ImmunityBio has launched the Phase 2 ResQ215B trial testing an outpatient, chemotherapy-free combination of CD19 t-haNK CAR-NK cells, rituximab, and ANKTIVA for relapsed indolent B-cell non-Hodgkin lymphoma, including Waldenström’s macroglobulinemia.
Written By: Samiksha Jadhav BPharm
Reviewed By: Pharmacally Editorial Team
ImmunityBio, Inc. has launched ResQ215B, a Phase 2 clinical study evaluating a new outpatient immunotherapy combination for patients with indolent B-cell non-Hodgkin lymphoma (iNHL), including Waldenström’s macroglobulinemia. This chemotherapy-free and lymphodepletion-free regimen is designed to deliver cellular immunotherapy without the toxicities or hospital stays often associated with conventional CAR-T therapies.
Patrick Soon-Shiong, M.D., Founder and Executive Chairman of ImmunityBio, described the platform as part of the company’s “Immunotherapy 2.0” vision, focused on achieving durable tumor control while avoiding many of the side effects of traditional treatments.
About the ResQ215B Trial
ResQ215B is testing ImmunityBio’s off-the-shelf CD19-targeted high-affinity natural killer (NK) cell therapy, known as CD19 t-haNK, in combination with rituximab, a standard anti-CD20 monoclonal antibody, and ANKTIVA® (nogapendekin alfa inbakicept), an IL-15 superagonist. Unlike CAR-T therapy, this approach does not require lymphodepleting chemotherapy, making it more accessible and feasible for outpatient care.
Phase 1 QUILT-106 Trial Backbone
The Phase 2 program builds on early findings from the Phase 1 QUILT-106 trial (NCT06334991), which evaluated CD19 CAR-NK cell therapy plus rituximab without ANKTIVA. In a small cohort of heavily pretreated Waldenström’s macroglobulinemia patients treated without lymphodepletion, all four participants achieved disease control. Two patients experienced rapid complete remissions lasting up to 15 months, while the remaining two achieved stable disease, including one patient with declining IgM levels. These results supported the potential of outpatient, off-the-shelf CAR-NK therapy without hospitalization.
Supporting Evidence for Adding ANKTIVA
The decision to add ANKTIVA in ResQ215B is supported by separate clinical evidence showing that IL-15–based immune stimulation may enhance antibody-driven activity. In a previously published Phase 1 study (NCT02384954, Foltz et al.), the IL-15 superagonist N-803 (the earlier development name for ANKTIVA) combined with rituximab achieved a 78% complete response rate in relapsed iNHL patients who had failed prior rituximab therapy. Importantly, this study did not include CAR-NK cells, but provides rationale that IL-15 agonists can strengthen rituximab-mediated immune effects.
ANKTIVA is designed to promote NK cell expansion, activate CD8+ T cells, and enhance antibody-dependent cellular cytotoxicity (ADCC) when paired with rituximab, potentially improving the depth and durability of responses when combined with CAR-NK therapy.
Chief Medical Officer Lennie Sender, M.D., noted that patients treated so far have received therapy in outpatient settings without major immune-related toxicities.
Study Design and Mechanism
ResQ215B is an open-label Phase 2 study enrolling adults with CD19-positive/CD20-positive indolent NHL, including Waldenström’s macroglobulinemia, who are relapsed or refractory after at least two prior therapies. Treatment is administered in 21-day outpatient cycles without preconditioning chemotherapy.
CD19 t-haNK, derived from NK-92 cells, offers dual anti-tumor activity: direct CAR-mediated killing of CD19-positive malignant B cells, and enhanced ADCC through high-affinity CD16 when combined with rituximab. By targeting both CD19 and CD20 pathways, the regimen is designed to reduce immune escape and improve response durability.
References
ImmunityBio Launches Phase 2 Chemotherapy-Free CAR-NK Cell Therapy Trial with ANKTIVA® (ResQ215B) in Indolent Lymphomas, 02 Feb 2026, https://immunitybio.com/immunitybio-launches-phase-2-chemotherapy-free-car-nk-cell-therapy-trial-with-anktiva-resq215b-in-indolent-lymphomas/
Study for Subjects with Relapsed/Refractory Non-Hodgkin Lymphoma, ClinicalTrials.gov ID NCT06334991, https://clinicaltrials.gov/study/NCT06334991
QUILT-3.002: N-803 in Patients with Relapse/Refractory iNHL in Conjunction with Rituximab, ClinicalTrials.gov ID NCT02384954, https://clinicaltrials.gov/study/NCT02384954
Foltz JA et al, Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma. Clin Cancer Res. 2021 Jun 15;27(12):3339-3350. Epub 2021 Apr 8. PMID: 33832946; PMCID: PMC8197753. https://doi.org/10.1158/1078-0432.ccr-20-4575