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

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

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) - 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 • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

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

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

Immunotherapy Before and After Surgery (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: ImmunityBio, Inc. | Initiation date: Jan 2025 ➔ May 2025

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

Current State of Bladder Preservation in High Grade Non-Muscle Invasive Bladder Cancer and Localized Muscle Invasive Bladder Cancer. (PubMed, Curr Oncol Rep) - "Approved novel therapies, including systemic pembrolizumab and intravesical agents such as nadofaragene, nogapendekin alfa inbakicept, and cretostimogene grenadenorepvec, have shown promising results for BCG-unresponsive NMIBC patients. Promising novel therapies, such as immunotherapy, recombinant intravesical therapies, and antibody-drug conjugates are emerging as potential alternatives. These therapies aim to achieve good oncological outcomes while maintaining quality of life, providing an alternative to the decades long standard of care."

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

Nogapendekin Alfa Inbakicept Displays Efficacy in BCG-Unresponsive NMIBC (OncLive) - P2/3 | N=190 | QUILT-3.032 (NCT03022825) | Sponsor: ImmunityBio, Inc. | "The IL-15 superagonist nogapendekin alfa inbakicept (NAI; Anktiva) displayed sustained complete response (CR) rates and a high rate of cystectomy avoidance in patients with high-risk BCG-unresponsive non–muscle–invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary disease, according to data from the phase 2/3 QUILT-3.032 trial (NCT03022825) presented during the 2025 American Urological Association Annual....Findings from the 36-month analysis of QUILT-3.032 demonstrated that in cohort A (n = 100), patients with BCG-unresponsive NMIBC with CIS with or without papillary disease treated with NAI plus BCG achieved a CR rate of 71% (95% CI, 61.1%-79.6%), with a duration of response (DOR) extending beyond 53 months as of the July 15, 2024, data cutoff. Further, 60% of responders maintained their response for at least 12 months."

P2/3 data • Bladder Cancer

Pre-clinical development of a masked tumor activated nectin-4 conditional IL-15 immuno-cytokine (ABBV-622) (AACR 2025) - "The hypothesis that tumor targeted IL-15 will enhance anti-tumor efficacy is supported by data that demonstrates ~ 80 % complete response rate of intravesicular Anktiva® in bladder cancer. Additionally, nectin-4 has also emerged as a promising target for patients with bladder cancer as PADCEV® recently received accelerated approval from the FDA...AbbVie participated in the interpretation of data, review, and approval of the publication. No honoraria or payments were made for authorship."

Late-breaking abstract • Preclinical • Bladder Cancer • Genito-urinary Cancer • Kidney Cancer • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • IFNG • IL15 • NECTIN4 • STAT5 • STAT5AWqe

Generation of cytokine-induced memory-like PD-L1 t-haNK (NK-92®) cells (AACR 2025) - "We show here that the Natural Killer cell line NK-92®, or 'activated' NK (aNKTM), can acquire a memory-like phenotype upon overnight induction with IL-12, IL-18, and the IL-15 superagonist N-803, as evidenced by increased steady-state IFNγ secretion (>50-fold increase) and up-regulation of CD25. This increase would then drive upregulation of PD-L1 expression on neighboring tumor cells, creating an expanding wave of targets sensitized to killing by PD-L1 t-haNK cells. A next generation, memory-like PD-L1 t-haNK cell line equipped with inducible safety switch features to remove the need for irradiation and extend their half-life in patients is being developed and would constitute a promising "off-the-shelf" cellular therapy against immunologically cold cancers."

IO biomarker • Oncology • IFNG • IL12A • IL18 • IL2RA • PD-L1

Immunogenic modulation with the ATR inhibitor tuvusertib enhances NK-mediated killing of prostate cancer [WITHDRAWN] (AACR 2025) - "Furthermore, tuvusertib treatment increased PD-L1 expression on the DU145 cells, which is associated with enhanced donor NK killing in the presence of avelumab and augmented sensitivity to PD-L1 t-haNK cells.Next, the anti-tumor effect of combining tuvusertib with N-803 (provided by ImmunityBio, Culver City, CA, USA) was investigated. Furthermore, tuvusertib synergized with N-803, resulting in a superior anticancer response. This provides a rationale for further investigation of this combination therapy."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TNFRSF10B

ImmunityBio to Showcase Advances for Bladder and Prostate Cancer at American Urological Association (AUA) Annual Meeting (Businesswire) - "ImmunityBio...will announce new clinical findings for ANKTIVA (nogapendekin alfa inbakicept-pmln) in non-muscle invasive bladder cancer carcinoma in situ (NMIBC CIS) and updated data on papillary disease without CIS at the American Urological Association Annual Meeting (AUA 2025)....Oral presentation provides update from QUILT-3.032 on durable complete responses to ANKTIVA plus BCG in BCG-unresponsive non-muscle invasive bladder cancer carcinoma in situ (NMIBC CIS) with or without Ta/T1 papillary disease and papillary disease alone. ImmunityBio to present keynote events on NMIBC and experience in prostate cancer, unveiling lymphopenia, the Absolute Lymphocyte Count (ALC) biomarker for all tumor types, and the ‘Cancer BioShield’."

Clinical data • Bladder Cancer • Prostate Cancer

Update of Product Revenue, Net Preliminary Results of Operations (Businesswire) - "With a permanent J-code (J9028) awarded in January 2025, ImmunityBio’s Q1 2025 ANKTIVA unit sales volume grew 150% over unit sales volume in Q4 2024; For the three-month period ended March 31, 2025, ImmunityBio achieved estimated net product revenue of approximately $16.5 million, surpassing net product revenue of $7.2 million in the prior quarter, a 129% quarter-over-quarter increase; ANKTIVA sales momentum continues to trend upward in 2025, with sales volume in March representing a 69% increase month-over-month from February."

Sales • Bladder Cancer

ImmunityBio Announces FDA Submissions of Supplemental BLA for NMIBC Papillary Disease (Businesswire) - "In Q1, ImmunityBio completed the submission to the FDA of an sBLA for the use of ANKTIVA plus BCG in BCG-unresponsive NMIBC in the papillary indication. Subject to regulatory approvals, the addition of the papillary indication expands the patient population benefiting from this therapy beyond the currently approved indication of bladder carcinoma in situ (CIS) with or without papillary disease and allows more patients to avoid the high morbidity and mortality associated with radical cystectomy. The data submitted to the FDA included efficacy results demonstrating durable complete remissions in patients with BCG unresponsive NMIBC papillary disease. In 88% and 82% of subjects, the probability of avoiding surgical removal of the bladder was achieved for as long as 2 and 3 years respectively, following treatment with ANKTIVA plus BCG."

FDA filing • Bladder Cancer

ImmunityBio Announces FDA Submissions for Expanded Access of ANKTIVA to Treat Lymphopenia (Businesswire) - "In Q2, the company submitted to the U.S. Food and Drug Administration (FDA) an Expanded Access Protocol (EAP) for ANKTIVA for the treatment of lymphopenia as a BioShield against the adverse effects of chemotherapy, radiation and checkpoint inhibitors, following authorization of a Regenerative Medicine Advanced Therapy (RMAT) designation for this indication in Q1."

FDA filing • Oncology

QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2/3 | N=190 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Oct 2028 ➔ Mar 2029 | Trial primary completion date: Apr 2025 ➔ Oct 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

The Power of ANKTIVA to Overcome Lymphopenia through NK & Memory T Cells to Achieve Durable Responses in Urological Diseases – Duration Matters | Sponsored by ImmunityBio (AUA 2025) - "Sponsored by ImmunityBio"

Lymphopenia • Hematological Malignancies • Urology