On June 2, 2025 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported long-term data, including the first report of median overall survival (OS) from the Phase 2 trial evaluating Ziihera (zanidatamab-hrii), a dual HER2-targeted bispecific antibody, in combination with chemotherapy for the investigational use in first-line HER2-positive (IHC 3+ or IHC 2+/FISH+) locally advanced nonresectable gastroesophageal adenocarcinoma (mGEA) (Press release, Jazz Pharmaceuticals, JUN 2, 2025, View Source [SID1234653640]). The data were featured as a rapid oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and the results were concurrently published in The Lancet Oncology.

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Among 41 patients with centrally confirmed HER2-positive tumors, treatment with Ziihera in combination with physician’s choice of chemotherapy resulted in a median progression-free survival (PFS) of 15.2 months [95% CI: 9.5, 33.4], and a median overall survival (OS) of 36.5 months [95% CI: 23.6, not estimable (NE)]. Median PFS remained stable with the additional four-year follow-up, consistent with previously reported results.

Among all 46 patients in the study with HER2-expressing mGEA, median PFS was 12.5 months [95% CI: 8.2, 21.8], and median OS also reached 36.5 months [95% CI: 23.6, NE], with the longest observed survival at 57.9 months (censored at data cutoff). Long-term follow-up also demonstrated low discontinuation rates, with no new safety signals observed.

"Gastroesophageal adenocarcinoma remains a highly aggressive cancer with a poor prognosis, even with currently available treatment options," said Dr. Elena Elimova, lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre, Toronto, Canada. "The long-term survival outcomes presented today at ASCO (Free ASCO Whitepaper) demonstrate the sustained antitumor activity achieved with zanidatamab plus chemotherapy over four years of follow-up. These results are especially encouraging given the high unmet need for better first-line treatment options for this patient population."

"These long-term survival data from our Phase 2 trial build on previously reported results and further strengthen our belief in Ziihera as a transformative treatment option for patients with HER2-positive disease," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "An estimated median overall survival of 36.5 months in this patient cohort is very encouraging given recent observations with standard of care regimens in similar populations, where median survival has typically ranged from 15 to 20 months. The sustained 15.2-month progression-free survival in the centrally confirmed HER2-positive subgroup after four years is a meaningful indicator of durable clinical benefit. We look forward to the top line results of the pivotal Phase 3 HERIZON-GEA-01 trial later this year and remain committed to advancing Ziihera across multiple tumor types."

Phase 2 mGEA Trial Results

The data include four-year follow-up and the first report of median OS from an ongoing, open-label Phase 2 trial (NCT03929666) evaluating Ziihera in combination with chemotherapy as a first-line treatment for patients with HER2-expressing mGEA, which includes gastric, esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with HER2-expressing mGEA (41 patients with centrally confirmed HER2-positive mGEA) were enrolled from 14 sites across the United States, Canada and South Korea. Patients received Ziihera with physician’s choice of chemotherapy, including fluoropyrimidine maintenance regimens. Chemotherapy-based regimens remain the current standard first-line treatment for mGEA.

The longer-term data (median duration of follow-up of 48 months [range, 29-59]) demonstrate the promising antitumor activity of Ziihera combined with chemotherapy as a first-line treatment for HER2-positive mGEA. In a post-hoc subgroup analysis of the 41 treated patients with centrally confirmed HER2-positive tumors, median PFS was 15.2 months [95% CI: 9.5, 33.4], and median OS was 36.5 months [95% CI: 23.6, NE]. These survival outcomes were consistent with prior analyses, with PFS durability maintained at the four-year follow-up. The confirmed objective response rate (cORR), the study’s primary endpoint, was 83.8% [95% CI: 68.0, 93.8], and median duration of response (DOR) was 20.4 months [95% CI: 8.3, 44.1]. These results further support the observed clinical benefit in this centrally confirmed population.

Among all 46 patients in the study, median PFS was 12.5 months [95% CI: 8.2, 21.8], and the estimated 24-month PFS rate was 31% [95% CI: 17%, 46%]. Median OS was also 36.5 months [95% CI: 23.6, NE], with an estimated 24-month OS rate of 65% [95% CI: 49%, 77%]. The cORR was 76.2% [95% CI: 60.5, 87.9], and median DOR was 18.7 months [95% CI: 10.4, 44.1].

With additional follow-up, the safety and tolerability profile of Ziihera plus chemotherapy showed low discontinuation rates, with no new safety signals identified. Diarrhea (39%) and hypokalemia (22%) were the most common Grade 3-4 treatment-related adverse events (TRAEs); the incidence of Grade 3 diarrhea was reduced from 52% to 24% for patients enrolled after the implementation of mandated antidiarrheal prophylaxis. There were no treatment-related deaths. Five patients discontinued Ziihera due to TRAEs.

Ongoing Phase 3 Trial
The Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating Ziihera in combination with standard of care chemotherapy with and without the addition of a PD-1 agent as a first-line treatment for HER2-expressing mGEA is currently underway. This is an events-based trial, and top-line results are expected to read out in the second half of 2025.

About Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide, and approximately 20% of patients have HER2-positive disease.i,ii,iii HER2-positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options. The overall prognosis for patients with GEA remains poor, with a global five-year survival rate of less than 30 percent for gastric cancer and about 19 percent for GEA.iv

About Ziihera (zanidatamab-hrii)
Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab-hrii with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.v In the United States, Ziihera is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.v The U.S. Food and Drug Administration (FDA) granted accelerated approval for this indication based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). v

Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. 

Important Safety Information for ZIIHERA

WARNING: EMBRYO-FETAL TOXICITY
Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients
of the risk and need for effective contraception.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity

ZIIHERA can cause fetal harm when administered to a pregnant woman. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA.

Left Ventricular Dysfunction

ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7). LVD resolved in 70% of patients.

Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions.

The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%.

Infusion-Related Reactions

ZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day.

Prior to each dose of ZIIHERA, administer premedications to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use.

If an IRR occurs, slow, or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs.

Diarrhea

ZIIHERA can cause severe diarrhea.

Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity.

ADVERSE REACTIONS

Serious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA.

The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%).

USE IN SPECIFIC POPULATIONS

Pediatric Use

Safety and efficacy of ZIIHERA have not been established in pediatric patients.

Geriatric Use

Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older.

No overall differences in safety or efficacy were observed between these patients and younger adult patients.

The full U.S. Prescribing Information for ZIIHERA, including BOXED Warning, is available at: View Source

On June 2, 2025 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported xM for treatment response monitoring (TRM), a liquid biopsy assay intended to detect molecular response to immune-checkpoint inhibitor (ICI) therapy in advanced solid tumors (Press release, Tempus, JUN 2, 2025, View Source [SID1234653656]). xM for TRM is the newest addition to Tempus’ growing portfolio of sensitive assays for monitoring molecular response and minimal residual disease (MRD). It is currently available for research use only, with clinical availability expected later this year.

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In 2023, an estimated 56.55% of patients with advanced or metastatic cancers were eligible for ICIs, with a corresponding estimated response rate of 20.13%.1 xM for TRM is designed to quantify changes in circulating tumor DNA (ctDNA) longitudinally from a blood sample, enabling early molecular response assessment in patients with advanced cancers receiving immunocheckpoint inhibitors (ICI) alone or combination therapies. xM for TRM leverages a unique multi-parametric algorithm, integrating copy number variations (CNVs), along with somatic and germline variant allele frequencies (VAFs), for a comprehensive and robust estimation of circulating tumor fraction.

Tempus is presenting new data on xM for TRM at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, highlighting the assay’s potential to help clinicians monitor response and refine treatment strategies for patients with advanced cancers.

Title: A molecular biomarker for longitudinal monitoring of therapeutic efficacy in a real-world cohort of advanced solid tumors treated with immune checkpoint inhibitors
Date/Time: June 2, 2025; 1:30 PM-4:30 PM CDT
Location: Poster Section Developmental Therapeutics—Immunotherapy (Poster #205)
Overview: Tempus xM for TRM, a liquid biopsy test, monitors treatment response by tracking ctDNA dynamics over time. Longitudinal non-molecular responders are associated with worse survival compared to molecular responders, highlighting the value of xM molecular response monitoring as a tool to guide ICI treatment decisions.
"Our comprehensive monitoring portfolio is designed to support patients throughout the cancer treatment journey," said Halla Nimeiri, MD, Chief Development Officer at Tempus. "We’re excited to introduce a new assay of molecular response for both physicians and biopharma researchers that can timely track changes of quantitative tumor fraction while patients receive ICI therapies. This may impact treatment decisions, especially for patients with advanced disease, where timing is absolutely critical. With xM for TRM, clinicians can detect molecular response to ICI prior to six weeks into treatment, enabling them to stay ahead of disease progression and optimize therapeutic strategies."

On June 2, 2025 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, reported the submission of the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for its lead drug candidate MaaT013, under the registered brand name of Xervyteg (Press release, MaaT Pharma, JUN 2, 2025, View Source [SID1234653591]). If approved, the Marketing Authorization would establish Xervyteg as the first microbiota therapeutic approved by the EMA, and the first one globally for a hematology indication. Xervyteg would also be the first approved therapy for the treatment of acute Graft-versus-Host Disease including gastro-intestinal involvement (GI-aGvHD) following 2 prior lines of systemic therapy.

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"Submitting our MAA to the EMA marks a major regulatory milestone for MaaT Pharma and a meaningful advancement for patients with refractory aGvHD—a life-threatening complication of stem cell transplantation with no approved therapies," said Hervé Affagard, Co-founder and CEO of MaaT Pharma. "We are now closer to providing a much-needed treatment option and remain deeply committed to advancing immunomodulating microbiota technologies in hemato-oncology, where new solutions are urgently needed."

While advancing toward the commercialization of Xervyteg (if approved) in Europe, MaaT Pharma is also actively exploring strategic partnerships to ensure broad access in timely fashion. The Company has active discussions with experienced partners who share its mission of delivering meaningful advancements to patients.

In parallel to the MAA submission, MaaT Pharma continues to provide access to Xervyteg in Europe and the U.S. through its Early Access Program (EAP)1 for patients with aGvHD and other indications. In 2024, physician demand for Xervyteg under the EAP (n=107) increased by 75% compared to 2023, driven by growing adoption across Europe and in the U.S. In France where the EAP first started, MaaT Pharma has captured 25% of the addressable market on a yearly basis in 2024. Overall, this position reflects the increasing recognition of Xervyteg as a valuable treatment option for GI-aGvHD patients.

aGvHD is the most severe complication of allogeneic stem cell transplantation, a standard-of-care treatment with curative intent offered to patients with blood cancers and some non-malignant hematological conditions. aGvHD refractoriness to current treatments is frequently encountered and severely impacts prognosis. In particular, patients with aGvHD failing both steroid and ruxolitinib typically exhibit a dismal prognosis, with a median survival of 28 days and 85% mortality at one year (Abedin et al 2021). Currently, no therapy is approved for third-line aGvHD, underscoring the urgent need for innovative therapies capable of improving survival and quality of life.

The MAA is supported by positive results from the Pivotal ARES study, a single-arm, open-label, multicenter European study evaluating the efficacy and safety of Xervyteg in GI-aGvHD as third-line therapy in 66 patients. Notably, the study met its primary endpoint, achieving a gastrointestinal overall response rate (GI-ORR) of 62% at Day 28, significantly exceeding the expected 38% response rate, and an overall response rate across all organs of 64% at Day 28. Among responding patients at Day 28, the majority exhibited full resolution of GvHD clinical manifestations (i.e., complete response), an important finding predictive of durable control of aGvHD clinical manifestations over time. The 12-month probability of survival was 54% (vs 15% Abedin et al, 2021). Importantly, patients who exhibited gastrointestinal response at Day 28 had a significantly better probability of survival than non-responders (67% vs 28% respectively, p <0.0001), indicating that Xervyteg-mediated aGvHD control is associated with a remarkable survival benefit. Additional secondary endpoints, including overall survival, will become available in late H2 2025. The Company also integrated supporting safety and efficacy data from 186 aGvHD patients2 treated under its ongoing EAP, which aligns with the positive topline results of the ARES trial and further supports Xervyteg’s strong efficacy and favorable safety profile in aGvHD.

The safety and tolerability of Xervyteg has been monitored by an independent Data Safety Monitoring Board (DSMB). In March 2025, the DSMB reviewed the overall safety of the trial (after all patients completed Day 28 visit or were discontinued earlier) and confirmed that "given the remarkable efficacy results, the study results show an acceptable safety profile and a favourable benefit /risk ratio". The DSMB members will continue to review safety on an ongoing basis until the 1-year follow-up.

The EMA will review the application under the centralized marketing authorization procedure and potentially a marketing authorization could be granted in H2 2026. This centralized procedure means that a single marketing authorization application can be submitted to the EU, and if granted by the European Commission, the authorization is valid in all EU Member States as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway.

On June 2, 2025 ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, reported 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 (Press release, ImmunityBio, JUN 2, 2025, View Source [SID1234653609]).

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To date no treatment exists for lymphopenia, a depletion of critical lymphocytes responsible for immunogenic cell death, specifically natural killer (NK) cells, killer CD8+ T cells and CD4+ with memory T cells. Treatment induced lymphopenia is a debilitating consequence of chemotherapy, radiation, and certain immunotherapies and steroids. This treatment-acquired immunodeficiency not only increases susceptibility to infections but also deprives the body’s immune system to fight residual or recurrent cancer, accelerating metastasis and disease progression, and contributing to early mortality. Countless publications over the last two decades has reported lymphopenia as a highly predictive biomarker of poor prognosis across all tumor types.1-6 Despite its significant clinical impact, the pharmaceutical industry has largely overlooked lymphopenia as a disease in its own right, and no approved therapies have existed to directly address it, until the approval of ANKTIVA in the treatment of BCG-unresponsive bladder cancer with the mechanism of action of an IL-15 superagonist proliferating key lymphocytes.7

While oncologists and patients have long had therapies such as EPOGEN and NEUPOGEN to manage chemotherapy- and radiation-induced anemia and neutropenia, no comparable option has been available for lymphopenia. ANKTIVA, an interleukin-15 (IL-15) agonist, is the first approved therapy with a defined mechanism of action to restore lymphocyte levels. It activates and proliferates NK and T cells without inducing immunosuppressive regulatory T cells (Tregs), offering the first solution for reversing this critical immune deficit of lymphocytes in cancer patients.7

"Lymphopenia has long been recognized as a major driver and predictor of early mortality in cancer—yet until now, it has remained unaddressed," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "This FDA authorization allows all patients with solid tumors suffering from immune collapse following first-line therapy of chemo, radiation, or immunotherapy to access ANKTIVA. The survival benefit we observed at ASCO (Free ASCO Whitepaper) 2025 in 3rd to 6th line advanced metastatic pancreatic cancer confirms that restoring lymphocyte levels—rather than depleting them—can change the course of disease."

At the 2025 ASCO (Free ASCO Whitepaper) 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. Highlighting the importance of lymphopenia reversal, Oncologist published a peer-reviewed paper titled "Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate," demonstrating that the patient with 2nd line metastatic pancreatic cancer treated with the full Cancer BioShield platform—including ANKTIVA, CAR-NK cells (PD-L1 t-haNK), and antigen-targeting adenoviruses—has remained in remission for over six years and maintains a high quality of life at the date of this release.

"We are entering a new era in oncology where the goal is not only to target the tumor but to protect and empower the immune system itself," continued Dr. Soon-Shiong. "Through this Expanded Access Program, we can now offer hope to patients with solid tumors who have exhausted standard options. Our mission is to transform cancer care by reversing the immune collapse that often leads to progression and mortality by enabling the body to serve as a factory for the regeneration and reconstitution of the lymphocytes key to immunogenic cell death of the tumor. By mitigating treatment induced lymphopenia from our standards of care, ANKTIVA can serve as a Cancer Bioshield."

In February 2025, ImmunityBio announced it had received a Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for ANKTIVA and CAR-NK (PD-L1 t-haNK) for the reversal of lymphopenia in patients receiving standard-of-care chemotherapy/radiotherapy and in relapsed locally advanced or metastatic pancreatic cancer. The RMAT designation is intended to expedite the development of therapies targeting serious or life-threatening conditions with unmet medical need.

Full results of our 2025 ASCO (Free ASCO Whitepaper) Annual Meeting can be found below:

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.
Abstract Text: View Source
Poster PDF: View Source

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.
Abstract Text: View Source
Poster PDF: View Source

About the Cancer BioShield Platform

The Cancer BioShield platform is a first-in-class immunotherapy strategy designed to restore immune competence by reversing lymphopenia—the loss of functional immune cells caused by cancer itself and by conventional treatments such as chemotherapy, radiation and immunotherapy. At its core is ANKTIVA (nogapendekin alfa inbakicept-pmln), an IL-15 agonist approved for BCG-unresponsive non–muscle-invasive bladder cancer CIS with or without papillary disease, activates and proliferates natural killer (NK) cells and CD4+ and CD8+ T cells, restoring lymphocyte levels critical for immunosurveillance, immunogenic cell death, and long-term tumor control.

The platform employs a multi-modal approach:

In-vivo stimulation: Subcutaneous administration of ANKTIVA expands NK and T cells, boosting anti-tumor immunity.
Ex-vivo targeted cytotoxicity: Off-the-shelf PD-L1 t-haNK CAR-NK cells are engineered to target and eliminate PD-L1–expressing tumor cells and immunosuppressive neutrophils (myeloid-derived suppressor cells), enhancing anti-tumor specificity and reducing immune evasion.
Memory Cytokine-Enriched Natural Killer (M-ceNK) cell therapy: M-ceNK cells are developed via cytokine activation and expansion of autologous and allogeneic NK cells collected through apheresis, potentially providing long-term immune memory and sustained cytotoxic capacity.
Together, these components offer a comprehensive, novel, immune-restoring therapeutic platform aimed at not only expanding effector immune cells, but also overcoming tumor-mediated immune suppression to support long-term disease control.

The platform’s effectiveness can be tracked through universally utilized simple complete blood count (CBC): increases in absolute lymphocyte count (ALC) reflect ANKTIVA’s lymphocyte-stimulating activity, while reductions in the neutrophil-to-lymphocyte ratio (NLR) demonstrate PD-L1 t-haNK’s immunosuppressive neutrophil targeting. Low ALC and high NLR levels6 are laboratory measurements that have been extensively reported as predictive biomarkers of poor prognosis with early mortality across all tumor types.1-6 The data presented by ImmunityBio for the first time demonstrates that improving ALC and NLR correlates with significant enhanced overall survival and clinical benefit.

With potential applications extending beyond oncology—including infectious disease, sepsis, and immune senescence—the Cancer BioShield Platform represents a potentially transformative shift in treating not just the tumor, but the underlying immune collapse that allows disease to progress.

About Lymphopenia and Absolute Lymphocyte Count (ALC)

Lymphopenia—the loss of key immune cells such as NK, CD4+, and CD8+ T cells—is a common side effect of chemotherapy1, radiation2,3, and some immunotherapies4. Unlike anemia and neutropenia, which have FDA-approved treatments like EPOGEN and NEUPOGEN, no therapy previously existed to treat this immune cell depletion. Lymphopenia weakens the immune system, increases infection risk, and is linked to early death across many cancer types.1-6 Low Absolute Lymphocyte Count (ALC) is a recognized poor prognostic marker. ANKTIVA is the first approved therapy to restore lymphocyte levels by activating and expanding NK and T cells—without increasing immunosuppressive T regulatory cells.

On June 2, 2025 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA"), a Phase 3 immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy, reported that Moffitt Cancer Center presented a Trial in Progress poster of the Company’s planned Phase 3 accelerated approval trial at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 1, 2025, in Chicago, Illinois (Press release, TuHURA Biosciences, JUN 2, 2025, View Source [SID1234653625]).

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The Company’s poster, titled "Multicenter, randomized, double-blinded, placebo-controlled trial of IFx-Hu2.0 (IFx) as adjunctive therapy with pembrolizumab (pembro) in checkpoint inhibitor (CPI)-naïve patients with advanced or metastatic Merkel cell carcinoma (MCC)" details the Company’s Phase 3 accelerated approval trial design of IFx-Hu2.0, its novel innate immune agonist. The Trial in Progress poster was presented by Andrew Brohl, M.D., Medical Oncologist at Moffitt Cancer Center, and highlighted the importance of innate immune system activation in Merkel cell carcinoma patients with primary resistance to checkpoint inhibitors (CPIs).

"Merkel cell carcinoma is a rare and aggressive tumor type. While checkpoint inhibitor therapy has markedly improved the outcome for patients with advanced or metastatic MCC, unfortunately for patients who don’t respond to first line checkpoint inhibitor therapy the survival is poor at less than 30 months.1 Based on the results from our Phase 1 clinical trials, IFx-Hu2.0 intralesional administration has demonstrated it can activate an innate immune response, resulting in the production and activation of tumor specific B cells and T cells, to overcome the primary CPI resistance in both advanced or metastatic MCC or melanoma," stated James Bianco, M.D., President and Chief Executive Officer of TuHURA Biosciences. "We believe we have provided data requested by the FDA that addresses the requirements listed in the partial clinical hold letter to allow us to initiate our Phase 3 accelerated approval trial this month. The FDA was constructive in the trial design, which can potentially satisfy both the requirements for accelerated and regular approval without the requirements for a post approval confirmatory trial. They continue to work with us under the SPA Agreement in preparing the trial’s initiation."

In the Phase 1b trial of IFx-Hu2.0, MCC among patients who progressed on pembrolizumab (anti-PD-1) or avelumab (anti-PDL-1) therapy, weekly administration of IFx-Hu2.0 for up to 3 doses followed by rechallenge with anti-PD(L)-1 therapy, demonstrated an overall response rate of 63% (2CR, 5 PR) with duration of responses ranging from 6 to 33 months with 5 ongoing responses as of last follow-up in June 2024.

The Company’s Phase 3 accelerated approval trial of adjunctive IFx-Hu2.0, to be conducted under a SPA agreement with the U.S. FDA, will evaluate IFx-Hu2.0 (0.1 mg) as an adjunctive therapy administered weekly for three weeks concurrent to pembrolizumab (200 mg) Q3W, compared to the same pembrolizumab regimen plus placebo. The pivotal trial is expected to enroll 118 CPI-naïve patients with advanced or metastatic MCC across approximately 22 to 25 U.S. sites. Trial participants will be randomized on a 1:1 basis and receive CPI therapy for up to two years, or until disease progression or CPI related toxicities. The primary endpoint for the trial is overall response rate (ORR) with a key secondary endpoint of progression free survival (PFS). Other secondary endpoints are safety, duration of response, and overall survival.

The Trial in Progress poster is available on the Scientific Publications page of TuHURA’s website.