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

Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment open • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jul 2026 ➔ Jan 2027 | Trial primary completion date: Jul 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Traditional and next-generation bacillus Calmette-Guérin based treatment strategies for bacillus Calmette-Guérin unresponsive non-muscle-invasive bladder cancer in the era of emerging therapies. (PubMed, Curr Opin Urol) - "Despite its limited efficacy as monotherapy in unresponsive cases, BCG retains therapeutic relevance as part of combination strategies that enhance its immunologic activity. Emerging data suggest that these BCG-based regimens offer a promising, bladder-sparing alternative for patients who are ineligible for or decline radical cystectomy. Ongoing and future trials will be essential to define optimal combinations and identify which patients are most likely to benefit, thereby enabling appropriate patient selection."

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

Nogapendekin alfa Inbakicept-pmln (Anktiva) with BCG: A Promising Arsenal in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer Intervention. (PubMed, Adv Pharm Bull) - No abstract available

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

A Phase 2, Open-label, Single-arm Study Of Autologous M-CENK Adoptive Cell Therapy And N-803 (IL-15 Superagonist) In Combination With Gemcitabine In Participants With Recurrent Platinum-Resistant High-Grade Ovarian Cancer (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: ImmunityBio, Inc. | Initiation date: Mar 2025 ➔ Nov 2024

Platinum resistant • Trial initiation date • Oncology • Ovarian Cancer • Solid Tumor

Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome (clinicaltrials.gov) - P2 | N=186 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Colon Cancer • Colorectal Cancer • Genetic Disorders • Oncology • Solid Tumor • EPCAM • MLH1 • MSH2 • MSH6

MHRA approves nogapendekin alfa inbakicept to treat adult patients with non-muscle invasive bladder cancer (GOV.UK) - "The Medicines and Healthcare products Regulatory Agency (MHRA) has today, 4 July 2025, approved nogapendekin alfa inbakicept (Anktiva) for adults with BCG-unresponsive non-muscle invasive bladder cancer, where the disease remains confined to the inner lining of the bladder and may include tumours....This medicine has been approved through the International Recognition Procedure (IRP)."

MHRA approval • Bladder Cancer

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

New P1 trial • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Emerging bladder-sparing treatments for high risk non-muscle invasive bladder cancer. (PubMed, Bladder Cancer) - "Emerging BSTs include immune checkpoint inhibitors like pembrolizumab and novel agents such as nadofaragene firadenovec and nogapendekin alfa inbakicept (IL-15)...Gene therapies and targeted agents like CG0070 and EG-70 are also gaining traction for their innovative mechanisms...Despite advancements, challenges remain in balancing efficacy, safety, and cost-effectiveness within diverse healthcare settings. This narrative review highlights the evolving landscape of BSTs for HR-NMIBC, emphasising the need for robust clinical evidence to refine patient selection and optimise outcomes."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • IL15

Impact of the IL-15 superagonist N-803 on lymphatic reservoirs of HIV. (PubMed, JCI Insight) - "Our findings suggest N-803 may reduce the HIV reservoir in LTs of PWH on ART, an effect likely mediated by enhanced NK cell function. Controlled studies assessing the impact of NK cell therapy on HIV LTs are needed."

Journal • Human Immunodeficiency Virus • Infectious Disease • KLRC1

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 2025) - P3 | "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 • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

A phase II prospective, open-label, multi-center, single-arm study of sasanlimab plus sacituzumab govitecan in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) pts: SSANTROP (APRO07-2022). (ASCO 2025) - "Pembrolizumab (Pem) was approved by the FDA based on Keynote-057 (41% complete response rate (CRR)) and offers a non-surgical option for pts who decline or are ineligible for RC. Nadofaregene firadenovec and Nogapendekin alfa inbakicept have been recently approved in this setting... This trial is the first to evaluate the combination of Sa and SG in BCG-unresponsive HR-NMIBC. With preliminary 3 mo CRR of 68%, the safety analysis identified no unexpected concerns, with severe AEs mainly involving neutropenia and febrile neutropenia. No treatment related toxic deaths occurred."

Clinical • P2 data • Alopecia • Anemia • Bladder Cancer • Dental Disorders • Fatigue • Febrile Neutropenia • Genito-urinary Cancer • Immunology • Neutropenia • Oncology • Solid Tumor • Stomatitis • Urothelial Cancer

Association of lymphopenia rescue and CA19-9 levels with overall survival following IL-15 superagonist N-803 and PD-L1 t-haNK chemo-immunotherapy for 3rd line or greater metastatic pancreatic cancer. (ASCO 2025) - P2 | "The multimodal chemo-immunotherapy protocol to induce immunogenic cell death resulted in OS that exceeded 6 months for both 3rd and ≥ 5th line patients, exceeding OS achieved by other therapies in this setting by ~2 months. It is notable that both favorable baseline ALC/CA19-9 and on-study higher ALC was associated with prolonged survival, given N-803's ability to increase both NK and CD8+/CD4+ T cells, the first FDA approved agent that proliferates lymphocytes in the face of lymphopenia. These findings support further investigation of this novel therapeutic regimen that includes PD-L1 t-haNK, and N-803 that, as an IL-15 superagonist, may be able to overcome lymphopenia and improve prognosis."

Clinical • Lymphopenia • Metastases • Hematological Malignancies • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9 • CD4 • CD8

QUILT 3.076 phase 1 study of memory-like cytokine-enriched natural killer (M-CENK) cells plus N-803 in locally advanced or metastatic solid tumors. (ASCO 2025) - P1 | "Preliminary efficacy objectives in cohort 2B are objective response rate (RECIST v1.1 and iRECIST criteria) and progression-free and overall survival evaluated using Kaplan-Meier methods. As of January 27, 2025, 15 participants have been enrolled in cohort 1, 21 participants in cohort 2 have undergone apheresis, and 10 participants have been treated with study therapies."

Metastases • P1 data • Immunology • Lung Cancer • Oncology • Solid Tumor • GZMB • IFNG • IL12A • IL15 • IL18

ImmunityBio Receives FDA Expanded Access Authorization for Landmark Treatment of Lymphopenia With ANKTIVA, the Cancer BioShield Platform, in Patients With Solid Tumors (Businesswire) - P2 | N=328 | QUILT-88 (NCT04390399) | Sponsor: ImmunityBio, Inc. | "ImmunityBio, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Expanded Access authorization for the use of its Cancer BioShield platform, anchored by ANKTIVA (nogapendekin alfa inbakicept-pmln), to treat lymphopenia in adult patients with refractory or relapsed solid tumors independent of tumor type who have progressed after first-line standard-of-care treatment, chemotherapy, radiation, or immunotherapy...At the 2025 ASCO Annual Meeting, ImmunityBio presented landmark results showing that reversing lymphopenia with ANKTIVA and CAR-NK therapy significantly prolonged median overall survival in third- to sixth-line metastatic pancreatic cancer patients. This benefit was further enhanced when treatment began at lower tumor burdens, as indicated by CA19-9 levels."

Commercial • P1 data • P2 data • Pancreatic Cancer • Solid Tumor

ASCO Report of Pioneering Treatment of Lymphopenia with Significant Overall Survival Benefit in Advanced Pancreatic Cancer (Businesswire) - P2 | N=328 | QUILT-88 (NCT04390399) | Sponsor; ImmunityBio, Inc. | "Landmark overall survival benefit (P-value 0.005, HR: 0.46 [0.26, 0.80]) observed in 3rd-6th line metastatic pancreatic cancer, correlated with reversal of lymphopenia; Patients with lower tumor burden and improved lymphocyte counts (ALC ≥1,000) had a median overall survival of 10.1 months, supporting earlier intervention in the disease course; These findings of improved survival in pancreatic cancer patients with lower tumor burden point to the potential of further prolonged overall survival in pancreatic cancer patients if treated in the first line or neoadjuvant stages of disease."

P2 data • Pancreatic Cancer

Matching-Adjusted Indirect Comparisons (MAIC) of TAR-200 vs FDA Approved Novel Agents in Bacillus Calmette-Guerin (BCG) Unresponsive High-Risk (HR) Non-Muscle Invasive Bladder Cancer (NMIBC) with Carcinoma in Situ (CIS) (ISPOR 2025) - "OBJECTIVES: FDA has approved pembrolizumab (pembro), nadofaragene firadenovec-vncg (nadofaragene), and nogapendekin alfa inbakicept-pmln (NAI) + BCG for the treatment of patients with BCG-unresponsive HR NMIBC with CIS. TAR-200 demonstrated statistically significant clinical benefit in CR rate at any time over FDA approved novel agents in BCG-unresponsive HR NMIBC with CIS and at first disease assessment compared to NAI + BCG. Further analyses will be conducted once additional follow-up is available for TAR-200."

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

Combination of a therapeutic cancer vaccine targeting the endogenous retroviral envelope protein ERVMER34-1 with immune-oncology agents facilitates expansion of neoepitope-specific T cells and promotes tumor control. (PubMed, J Immunother Cancer) - "This study reveals the potential of a vaccine that targets the retroviral envelope protein ERVMER34-1 and supports its continued development toward clinical testing as a new class of therapeutic cancer vaccine."

IO biomarker • Journal • Eye Cancer • Head and Neck Cancer • Infectious Disease • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • IL15

ImmunityBio Reports Doubled Net Revenue and 150% Unit Growth in Q1 2025, With Continued Strong Sales Momentum in First Quarter since J-code (Businesswire) - "ANKTIVA unit sales volume in Q1 2025 grew 150% over Q4 2024, with monthly volume in March up 69% over February. Nearly 200 urology practices across the United States are in the process of registering for ImmunityBio’s recombinant BCG (rBCG) Expanded Access Program (EAP), reflecting continued progress in ImmunityBio’s efforts to address the Bacillus Calmette-Guérin (BCG) shortage and broaden the market for ANKTIVA."

Sales • Bladder Cancer

Altered viral rebound dynamics in chronically treated people with HIV given long-acting broadly neutralizing antibodies and N-803 (IAS-HIV 2025) - "The embargo on all abstracts, including oral abstract, poster exhibition, e-poster and late breakers, will lift on Monday, 14 July 2025, at 15:30 Central African Time (CAT). If an abstract is part of an official IAS 2025 press conference that occurs before that time, the embargo on that abstract lifts at the start of the official press conference."

Human Immunodeficiency Virus • Infectious Disease

QUILT-3.076: Study of Autologous M-CENK in Subjects With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD4

Expanded Access Use of Nogapendekin-alfa Inbakicept for the Treatment of Lymphopenia Induced by Chemotherapy, Radiation, and Checkpoint Inhibitors (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: ImmunityBio, Inc.

Checkpoint inhibition • New trial • Oncology

Immunotherapy With N 803, ETBX-071, and M-CENK in Combination With Radiation for Participants With High-Risk Prostate Cancer. (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: ImmunityBio, Inc. | Initiation date: Jan 2025 ➔ Jun 2025

Trial initiation date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ResQ201A: Clinical Trial Of N-803 Plus TISLELIZUMAB And DOCETAXEL Versus DOCETAXEL Monotherapy In Participants With Advanced Or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=460 | Recruiting | Sponsor: ImmunityBio, Inc. | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Monotherapy • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ImmunityBio Requests an Urgent Meeting With FDA to Address the Change in the Agency’s Unambiguous Guidance on Jan 2025 to Submit a sBLA for NMIBC BCG Unresponsive Papillary Disease, Following an Inconsistent Refusal to File Letter on May 2, 2025 (Businesswire) - "ImmunityBio, Inc...announced that the Company received a Refusal to File (RTF) letter from the U.S. Food and Drug Administration (FDA) for the supplemental biologics license application (sBLA) for use of ANKTIVA plus Bacillus Calmette-Guerin (BCG) in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) for the indication of papillary disease. This RTF letter was received despite reaching unanimous guidance and encouragement at the in-person January 2025 meeting from the leadership of the Agency, including from CBER, CDER and OCE to submit this sBLA....Relying on this unanimous guidance the Company submitted the sBLA in March 2025. The Company has already requested an urgent meeting to resolve the inconsistencies between the directives provided at the January Meeting and receipt of the RTF letter."

FDA event • Bladder Cancer