Phase 2 Trial Will Evaluate CD19 t-haNK Combo in Indolent Lymphomas

ResQ215B (NCT07125872), a phase 2 clinical study, was initiated to evaluate an off-the-shelf CD19-targeted high-affinity natural killer (NK) cell therapy, CD19 t-haNK, in combination with nogapendekin-alfa inbakicept-pmln (Anktiva) and rituximab (Rituxan) in patients with indolent B-cell non-Hodgkin lymphoma (NHL), including Waldenström Macroglobulinemia, according to a news release from the developer, ImmunityBio, Inc.

The trial was designed to investigate the efficacy of the interleukin-15 (IL-15) superagonist in combination with an off-the-shelf CD19-targeted natural killer (NK) cell therapy and rituximab for individuals who experienced disease progression after prior treatment. Investigators initiated this study to establish a more outpatient treatment paradigm that may avoid the toxicities associated with conventional lymphodepleting chemotherapy. By stimulating both the innate and adaptive branches of the immune system, the research team aims to improve the depth and durability of anti-tumor activity in individuals with relapsed or refractory disease.

Efficacy findings from the Phase 1 QUILT-106 study (NCT06334991), which evaluated the combination of CD19 CAR-NK cells and rituximab without the addition of nogapendekin-alfa inbakicept or chemotherapy, supported the start of the phase 2 ResQ215B trial. In the phase 1 study, a disease control rate (DCR) of 100% was observed among the first 4 patients treated for Waldenström Macroglobulinemia. Additionally, complete remissions (CRs) were reported in 2 patients, which were ongoing at 7 and 15 months of follow-up, respectively, and no subsequent treatment was delivered.

Furthermore, investigators noted results from the previously published phase 1 QUILT-3.002 trial (NCT02384954), which demonstrated that nogapendekin-alfa inbakicept combined with rituximab achieved a 78% CR rate in patients with relapsed indolent NHL who had previously experienced progression following rituximab monotherapy.

“Our BioShield platform, which combines cell therapy, our IL-15 superagonist, and a monoclonal antibody in an outpatient, chemotherapy-free setting, represents our vision for Immunotherapy 2.0,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio, said in the news release. “Building on the durable [CRs] observed with our CD19 CAR-NK cell therapy plus rituximab in Waldenström Macroglobulinemia, we are now adding [nogapendekin-alfa inbakicept] to further arm the immune system. We believe this off-the-shelf immunotherapy platform can trigger powerful anti-tumor activity without the toxicities of traditional treatments, potentially transforming the treatment paradigm for patients with indolent B-cell malignancies.”

The ResQ215B phase 2 study is an open-label trial enrolling adults with CD19-positive and CD20-positive indolent NHL. Eligible subtypes for the study include follicular lymphoma and Waldenström Macroglobulinemia. Patients are required to have relapsed or refractory disease following at least 2 prior lines of therapy. Treatment will be given in 21-day cycles in the outpatient setting without preconditioning chemotherapy.

The developers engineered CD19 t-haNK as an allogeneic NK-92-based cell therapy genetically engineered to express a CD19-specific chimeric antigen receptor and a high-affinity CD16 receptor. This dual engineering allows the cells to target CD19-expressing malignant B cells directly through CAR-mediated cytotoxicity while augmenting antibody-dependent cellular cytotoxicity when paired with the anti-CD20 antibody rituximab.

“A therapy that does not require apheresis, individualized manufacturing, chemotherapy, or inpatient hospitalization would represent an important advance for patients with [indolent] NHL, who are regarded as having incurable lymphomas,” Lennie Sender, MD, chief medical officer for Cell Therapy and Liquid Tumors at ImmunityBio, stated in the release. “To date, all treated patients have received the therapy in an outpatient setting without significant immune-related toxicities, demonstrating the feasibility of delivering potent cellular therapy without hospital admission. With ResQ215B, we will evaluate whether adding [nogapendekin-alfa inbakicept] can further improve response rates and durability while maintaining this favorable safety profile.”

Reference

ImmunityBio launches phase 2 chemotherapy-free CAR-NK cell therapy trial with ANKTIVA® (ResQ215B) in indolent lymphomas. News release. ImmunityBio. February 2, 2026. Accessed February 2, 2026. https://tinyurl.com/yckfyj5h