Anktiva (nogapendekin alfa inbakicept-pmln) / ImmunityBio - LARVOL DELTA

Reduction of the HIV-1 reservoir in T cells from people with HIV-1 on suppressive antiretroviral therapy using expanded natural killer cells. (PubMed, mBio) - "Notably, eNK cells from PLWH on ART efficiently killed autologous HIV-1+ T cells reactivated by a combination of vorinostat (SAHA) and IL-15 or an IL-15 superagonist (N-803), as evidenced by declines in proviral load, inducible HIV-1 mRNA, and virus release. Current strategies for this potential eradication include using HIV latency-reversing agents (LRAs), ex vivo expansion of natural killer (NK) cells, and improving the ability to kill infected cells with broadly neutralizing antibodies against HIV. Here, we demonstrate that NK cells from PLWH can be expanded outside the body into "eNK" cells that specifically attack HIV-infected cells without harming uninfected ones, significantly reducing HIV reservoirs in vitro after LRA treatment."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4 • IL21

IL15 Superagonist (N-803, Anktiva) + Checkpoint Inhibitor (CPI) Prolongs OS in 2ndline or Greater NSCLC Patients Failing CPI (IASLC-WCLC 2024) - "QUILT 3.055, a phase 2b study of Anktiva in combination with CPI (nivolumab or pembrolizumab) in multiple tumor types including NSCLC who failed CPI. The KM curve demonstrates long-term survival at ≥18 and ≥21 months of 28/86 (33%) and 26/86 (30%) patients respectively: Conclusions : Anktiva plus CPI therapy in 2 nd line or greater NSCLC demonstrated long-term median OS, independent of PDL1 status, and independent of prior lines of therapy in patients with acquired resistance to CPI. These findings support the novel mechanism of action of Anktiva to rescue CPI activity through the activation of NK and T cells, driving long-term memory, with median OS ongoing survival of 33% and 30% at 18 and 21 months respectively, exceeding the standard of care."

Checkpoint inhibition • Clinical • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • IL15 • PD-L1

ImmunityBio, Inc…announced the launch of ResQ215B, a Phase 2 clinical study evaluating a novel chemotherapy-free and lymphodepletion-free combination immunotherapy in patients with indolent B-cell non-Hodgkin lymphoma (iNHL), including Waldenström’s Macroglobulinemia. (Businesswire) - "ResQ215B builds on promising results from the Phase 1 QUILT-106 study (NCT06334991), which evaluated CD19 CAR-NK cell therapy in combination with the anti-CD20 rituximab (without ANKTIVA)....First Phase 2 chemotherapy-free, lymphodepletion-free, off-the-shelf CAR-NK cell therapy plus ANKTIVA and rituximab regimen to be evaluated in indolent non-Hodgkin lymphoma (iNHL), including Waldenström’s Macroglobulinemia."

Trial status • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia

Prolonged Progression-Free Survival, Disease-Free Survival and Cystectomy Avoidance with IL-15 Receptor Lymphocyte-Stimulating Agent NAI plus BCG in BCG-Unresponsive Papillary-Only NMIBC. (PubMed, J Urol) - P2/3 | "In QUILT-3.032, the efficacy of IL-15 receptor agonist, nogapendekin alfa inbakicept (NAI) in combination with BCG for BCG-unresponsive high-grade papillary-only non-muscle invasive bladder cancer (NMIBC) was assessed...Most TRAEs were grade 1-2 (61%) with 3% grade 3, and no grade 4-5. The 12- and 36-month DFS, PFS, DSS, and cystectomy avoidance rates demonstrate the effectiveness and safety of NAI plus BCG in the management of BCG-unresponsive papillary disease."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • IL15

FLINN: First-Line Ipilimumab Plus Nivolumab and Nogapendekin Alfa Inbakicept (N-803) in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=26 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Phase II evaluation of combination immunotherapy with CV301, N-803, bintrafusp alfa, and M9241 in patients with advanced small bowel and colorectal cancers. (ASCO-GI 2023) - P2 | "All patients had received prior 5-fluorouracil-based treatment, with 29/30 (96.7%) having received ≥ 2 lines of systemic therapy. Combination therapies with CV301, N-803, bintrafusp alfa, and M9241 had manageable safety profiles. Preliminary clinical activity was observed in patients with advanced MSS/pMMR small bowel or CRC. Median OS was promising as compared to historical median survivals of 6-7 months following receipt of multiple lines of therapy."

Clinical • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IL12A • MUC1 • TGFB1

Exceptionally selective voltage-sensor trapping of NaV1.5 channels by Mg-protoporphyrin impairs cancer cell migration. (PubMed, Sci Rep) - "A mutagenesis study and structural modeling reveals that MgPpIX stabilizes the domain-II voltage sensor in the deactivated conformation, with residues E795 and N803 being relevant determinants. MgPpIX also inhibits native NaV channels in breast cancer MDA-MB-231 and colorectal carcinoma SW-480 cell lines, and suppresses cell migration. MgPpIX is an exceptionally potent and specific inhibitor of hNaV1.5 and may serve as a lead compound in anti-cancer drug development."

Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • NAV1

First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer. (PubMed, J Hematol Oncol) - P1 | "CIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI."

Journal • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • CD8

CARMEN-803: N-803 Maintenance Therapy Post CAR T-cell Therapy in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=13 | Not yet recruiting | Sponsor: University of Utah | Trial completion date: Sep 2031 ➔ Dec 2031 | Trial primary completion date: Sep 2030 ➔ Dec 2030

Trial completion date • Trial primary completion date • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Evolving Pharmacotherapy for Bladder Cancer-From Non-Muscle-Invasive to Metastatic Disease-Development of Novel Therapies for BCG-Unresponsive NMIBC (PubMed, Gan To Kagaku Ryoho) - "Bladder cancer is a common malignancy in the elderly, with approximately 75% of cases diagnosed as non-muscle-invasive bladder cancer(NMIBC).Although transurethral resection of bladder tumor(TURBT)is the standard initial treatment, recurrence rates remain high, and intravesical Bacillus Calmette-Guérin(BCG)instillation has long been used as an adjuvant therapy.However, about 30% of patients develop BCG-unresponsive disease despite adequate BCG administration.Radical cystectomy is recommended in such cases, but its invasiveness and impact on quality of life(QOL)often make it impractical in real-world settings.Thus, the development of novel bladder-preserving treatments is urgently needed.In recent years, diverse approaches including immune checkpoint inhibitors(ICI), gene therapy, drug delivery systems(DDS), and oncolytic virus-based therapies have been actively investigated, with numerous clinical trials ongoing worldwide.Importantly, pembrolizumab, nadofaragene..."

Journal • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). (ASCO 2022) - P2/3 | "Pembrolizumab was approved in 2020 with a 41% complete response (CR) rate in a single arm phase 2 trial of 96 patients. In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response, and 53% DFS rate at 18 months in Papillary disease. Cystectomy was avoided in over 90% of patients with 2 years of follow-up."

Clinical • Bladder Cancer • Fatigue • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD8 • IL15

ABLE-22: Safety and efficacy evaluation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy—A randomized, open-label, phase 2 study. (ASCO-GU 2025) - P2 | "Bladder-preserving treatment options for patients with BCG-unresponsive NMIBC with CIS ± Ta/T1 include intravesical gene therapy (nadofaragene firadenovec-vncg), intravesical chemotherapy (gemcitabine and docetaxel), and immunotherapy (intravenous pembrolizumab and intravesical nogapendekin alfa inbakicept-pmln). Exploratory endpoints include changes in expression of potential biomarkers in blood and urine. Results from this investigational, randomized, multicenter, open-label study evaluating the safety and efficacy of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy are expected July 2028."

Clinical • Combination therapy • IO biomarker • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A national perspective on the management of high-risk BCG-unresponsive non-muscle-invasive bladder cancer in Romania. (PubMed, Arch Ital Urol Androl) - "Though RC remains the predominant approach for BCG-unresponsive cases, over half of urologists' report using intravesical chemotherapy, reflecting interest in bladder-sparing strategies rather than newly approved FDA agents."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ImmunityBio Reports Median Overall Survival Not Yet Reached and Lymphopenia Reversed in Recurrent Glioblastoma Patients Receiving ANKTIVA Plus CAR-NK, Chemo-Free Therapy (Businesswire) - "Primary endpoint of QUILT-3.078 is overall survival; median overall survival has not yet been reached, with 19 of 23 enrolled patients alive as of January 22, 2026; Fourteen patients have evaluable data, with the longest survival from time of disease recurrence reaching 12 months to date and ongoing; Baseline mean absolute lymphocyte count (ALC) among these 14 patients was 0.9 x 103/uL, confirming severe lymphopenia at enrollment; ALC increased within one treatment cycle, with mean ALC rising to ≥ 1.4 x 103/uL (p <0.001, N=14)."

P2 data • Glioblastoma

INTERRUPT-HIV: Interleukin-15 to Promote Post-ART Control of HIV (clinicaltrials.gov) - P2 | N=20 | Enrolling by invitation | Sponsor: Michael Peluso, MD | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

An Update on QUILT-3.032: Complete Responses to N-803 plus BCG Therapy in BCG-Unresponsive Bladder Carcinoma In Situ (CIS) With or Without Ta/T1 Papillary Disease (AUA 2025) - P2/3 | "These findings derived from the fully-enrolled cohort A of QUILT 3.032, demonstrate the stability of the CR rate and confirm the durability of responses in participants with BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease. They further demonstrate a positive association between achievement of a CR and both PFS and cystectomy avoidance. These updated results, together with previously reported safety and quality-of-life, indicate a favorable risk:benefit ratio for patients with bladder CIS +/- Ta/T1 papillary disease treated with N-803 plus BCG."

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

N-803 plus BCG Complete Response rate in NMIBC CIS subjects: BCG refractory, relapsed, checkpoint failure, and chemotherapy failure; updated results (QUILT 3.032) (AUA 2024) - P2/3 | "N-803 plus BCG results in a high CR rate in subjects who failed both BCG and other therapies, including additional BCG, chemotherapy and checkpoint inhibitors, with a median duration of response of >28 months."

Clinical • Bladder Cancer • CD8 • IL15

ImmunityBio, Inc…announced that it recently held a Type B End-of-Phase meeting with the U.S. FDA regarding the Company’s supplemental Biologics License Application (sBLA) for ANKTIVA (nogapendekin alfa inbakicept) plus Bacillus Calmette-Guérin (BCG) in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with papillary tumors. (Businesswire) - "The Company presented an overview of the clinical status of its papillary disease program, including more than five years of follow-up data...the FDA recommended that the Company provide certain additional information for its consideration to support a potential resubmission of the sBLA initially submitted in 2025 for the papillary indication. ImmunityBio has compiled the requested information and will submit it to the Agency within the next 30 days. This additional information does not contemplate the initiation or design of a new clinical trial...The proposed submission for the BCG-unresponsive NMIBC papillary indication is supported by long-term results from the QUILT-3.032 Phase 2/3 trial (Cohort B) in 80 patients with BCG-unresponsive high-grade papillary-only NMIBC."

FDA event • Bladder Cancer

The Quadruple Immunotherapy for Colorectal Cancer (QuICC) Trial for Mismatch Repair-Proficient Metastatic Colorectal Cancer. (PubMed, Oncologist) - P2 | "Quadruplet therapy produced one objective response in unselected mCRC patients (n = 20). There were no responses with triplet therapy (n = 12). The role of ICB-based combination immunotherapy in pMMR CRC remains unclear. NCT04491955."

Journal • Mismatch repair • pMMR • Colorectal Cancer • Oncology • Solid Tumor • IL12A • IL15 • MUC1 • TGFB1

The randomized QUILT-2.005 trial in BCG-naïve patients comparing BCG alone to BCG plus ANKTIVA is ongoing, and enrollment has exceeded expectations. (Businesswire) - "Enrollment is on track to be completed by Q2 2026, with a potential BLA submission by year-end."

Enrollment status • FDA filing • Bladder Cancer

Saudi FDA Grants Accelerated Approval to ImmunityBio’s ANKTIVA for Non-Muscle Invasive Bladder Cancer with Carcinoma In-Situ (Businesswire) - "Approval of ANKTIVA was granted for BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ, with or without papillary disease, based on review of data from QUILT-3.032...ImmunityBio plans to open a regional office in the Kingdom of Saudi Arabia to support physicians and health systems across the Middle East and North Africa."

Accelerated approval • Approval • Bladder Cancer

ImmunityBio Announces Durable Complete Response of 15 Months with a Chemotherapy-Free CD19 CAR-NK Cell Therapy in Waldenstrom Lymphoma (ImmunityBio Press Release) - "Updated follow-up demonstrates sustained complete responses with durations now extending to 15 months and ongoing, with 100% disease control observed to date...To date four patients with Waldenstrom Non-Hodgkin Lymphoma have been enrolled and all remain in clinical disease control. Two patients are evaluable for long-term follow-up and continue to demonstrate durable complete remission at 7 and 15 months and ongoing, respectively, despite receiving no additional treatment after the initial eight doses of immunotherapy....A follow-up study is being designed to test the further combination of the NK-CAR with ANKTIVA (nogapendekin alfa inbakicept; N-803), a superagonist IL-15, and rituximab to build on the success of the QUILT-106 in indolent lymphoma including Waldenström’s Macroglobulinemia."

New trial • P1 data • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia

Interim analysis requested by FDA demonstrated statistically significant longer duration of complete response with ANKTIVA + BCG (Businesswire) - "The interim analysis demonstrated that ANKTIVA significantly prolonged the duration of complete response when combined with BCG compared to BCG alone in the BCG-naïve NMIBC setting. At six months, 85% of patients receiving ANKTIVA plus BCG maintained a complete response, compared with 57% of patients receiving BCG alone. At nine months, 84% of subjects in the experimental arm maintained a complete response, while subjects receiving BCG alone demonstrated a complete response rate of 52%."

P1/2 data • Bladder Cancer

The combination of ANKTIVA plus checkpoint inhibitor therapy is protected by multiple issued patents, including U.S. Patent Nos. 9,925,247 and 11,071,774, with patent terms extending into 2032–2039. (Businesswire)

Patent • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer

ImmunityBio Announces Positive Results Demonstrating ANKTIVA as a Lymphocyte Stimulating Agent in Combination With Checkpoint Inhibitors in Non-Small Cell Lung Cancer (Businesswire) - "In first-line NSCLC (QUILT-2.023), a randomized study demonstrated a statistically significant and sustained increase in absolute lymphocyte count (ALC) from baseline with ANKTIVA plus CPI compared with CPI alone (p=0.0065)...In second- and later-line NSCLC (QUILT-3.055)...Responders receiving ANKTIVA plus CPI experienced significantly longer overall survival compared with non-responders (median OS 16.2 vs 11.8 months; HR 0.52; p=0.0369), directly linking immune restoration to clinical benefit...Detailed results from QUILT-2.023 and QUILT-3.055 are being prepared for peer-review publication and future scientific presentations...Enrollment was closed early following changes in the first-line NSCLC treatment landscape."

Enrollment closed • P2b data • P3 data • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer