On October 19, 2025 NETRIS Pharma, a clinical-stage biotechnology company pioneering novel therapies targeting Netrin-1 to overcome resistance to chemotherapy and immunotherapy, reported the presentation of the first results from its ongoing Phase 2 clinical trial IMMUNONET. The Study evaluates NP137 in combination with anti–PD-1/PD-L1 therapies with advanced solid tumors. The data will be shared in a poster session at the upcoming ESMO (Free ESMO Whitepaper) Oncology Congress 2025 in Berlin, Germany.

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Resistance to Immune Checkpoint Inhibitors (ICI) remains a major challenge in the treatment of solid tumors such as non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC). Netrin-1, an embryonic guidance factor re-expressed in various cancers, contributes to tumor resistance and epithelial-to- mesenchymal transition (EMT). NP137, a first-in-class monoclonal antibody targeting Netrin-1, has demonstrated the ability to inhibit EMT and modulate the tumor microenvironment, thereby potentially restoring sensitivity to immunotherapy.

IMMUNONET (NCT05605496) was designed to evaluate whether NP137 was able to (re)-sensitize solid tumors to ICI. Patients who had progressed under a prior anti–PD-1/PD-L1 were enrolled to receive NP137 as an add–on to their immunotherapy. They were enrolled in 3 distinct cohorts depending on their best response and time to progression (cohort 1, stable disease; cohort 2, primary refractory and cohort 3, secondary refractory). The study was designed as a 2-stage adaptive design. This poster reports the results of stage 1. In cohort 3 (secondary refractory) where a majority of NSCLC and HNSCC patients were enrolled, the primary endpoint of Progression-Free Rate at 12 weeks (PFR-12W) was met ahead of stage 2. These results strongly suggest the efficacy of combining NP137 with anti–PD-1/PD-L1 therapy in this difficult-to-treat population and warrant further controlled studies to confirm these findings.

Importantly, the combination of NP137 with ICI was very well tolerated. « These preliminary results are particularly encouraging » said Dr Jérome Fayette, M.D., Ph.D., Principal Investigator of the study. « Patients who have progressed after prior anti–PD-1/PD-L1 therapy represent one of the most difficult populations to treat. The encouraging efficacy and safety results observed in this study strongly support the continued clinical development of NP137. Advancing to a confirmatory randomized study will allow to further validate these findings and better define the therapeuticpotential of NP137 in combination with immune checkpoint inhibitors for patients with advanced solid tumors ».

« Observing durable disease control in this setting supports the concept that targeting Netrin-1 can re-sensitize tumors to immune checkpoint inhibition » added Dr. Sébastien Hazard, Chief Medical Officer of NETRIS Pharma. « Combining NP137 with checkpoint inhibitors may offer a new option for patients who no longer benefit from standard immunotherapy ».

Poster Details

Title: NP137 combined with anti–PD-1/PD-L1 therapy in ICI-pretreated solid tumors: Interim efficacy and safety results from the IMMUNONET study
Session: 966P
First Author: Dr. Jerome Fayette
About EIC Accelerator

The EIC Accelerator supports individual Small and Medium Enterprises (SMEs), in particular Startups and spinout companies to develop and scaleup game-changing

innovations. ImmunoNET is co-funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or NETRIS Pharma. Neither the European Union nor NETRIS Pharma can be held responsible for them.

(Press release, Netris Pharma, OCT 19, 2025, View Source [SID1234656772])

On October 19, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on developing innovative CAR T-cell therapies, reported that the research results of the Phase Ib registrational clinical trial of satricabtagene autoleucel ("satri-cel", CT041) (an autologous CAR T-cell product candidate against protein Claudin18.2) for pancreatic cancer (PC) adjuvant therapy in China (CT041-ST-05, NCT05911217) has been presented in poster session at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025. The poster was titled "Adjuvant Therapy with Claudin18.2-specific CAR T Cells (Satri-cel) in High-Risk Pancreatic Cancer (CT041-ST-05)" (Poster number: 2220P). The trial represents the world’s first proof-of-concept (POC) study exploring CAR T-cell therapy for the adjuvant treatment of solid tumors. Professor Xianjun Yu from Fudan University Shanghai Cancer Center serves as the principal investigator.

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dismal prognosis even among patients who undergo surgical resection. Local recurrence and distant metastasis are common, often leading to treatment failure. Elevated carbohydrate antigen 19-9 (CA19-9) levels post resection indicate aggressive tumor biology and higher risk of recurrence. The median interval is approximately 3 months between CA19-9 elevation and radiological recurrence. [1][2] Current standard adjuvant therapies have limited effectiveness for high-risk patients, highlighting the urgent need for novel strategies.

This trial enrolled patients with Claudin18.2 positive PDAC who have undergone curative-intent resection, with abnormal CA19-9 after 3 months adjuvant chemotherapy and no evidence of recurrence. From Sep 15, 2023 to April 11, 2025 (data cut-off date), six patients received satri-cel infusion and completed at least 4 weeks of follow-up.

With a median follow-up of 6.05 months from infusion, only one patient experienced disease recurrence, while others are still under disease free. The median disease-free survival (DFS) and median overall survival (OS) were not reached (NR). The 9-month DFS rate from surgery was 83.3%. Notably, one patient who has completed 52-week follow-up post infusion is still under follow-up without disease recurrence. Moreover, significant decline in CA19-9 levels post infusion was observed in five (83.3%) patients, with reductions ranging from 51.3% to 96.1%.

All patients developed Grade 1 or 2 cytokine release syndrome (CRS) after the first satri-cel infusion. For the second infusion administered in one patient, grade 3 CRS accompanied by hypotension was observed, which was resolved within three days following tocilizumab treatment. All patients experienced gastrointestinal disorders, such as nausea and vomiting, which were all Grade 1 or 2. Only one case of Grade 3 gastritis occurred. No immune effector cell-associated neurotoxicity syndrome (ICANS) was reported.

Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, said, "We are pleased to see that satri-cel has shown promising preliminary efficacy with a manageable safety profile in the highly challenging setting of pancreatic cancer adjuvant therapy. For patients at high risk of recurrence after surgical resection of pancreatic cancer, there are currently very few effective treatment options. In this trial, the sustained disease-free survival and marked declines in CA19-9 levels suggest that satri-cel, an innovative cellular immunotherapy, may clear minimal residual disease and potentially alter the disease course for these patients. Furthermore, we are actively advancing clinical trials exploring satri-cel for gastric cancer adjuvant therapy and as a sequential treatment following first-line gastric cancer therapy, with the goal of providing better curative opportunities for a broader patient population."

About Satri-cel
Satri-cel is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be the first-in-class globally. Satri-cel targets the treatment of Claudin18.2-positive solid tumors with a primary focus on gastric/gastroesophageal junction adenocarcinoma (G/GEJA) and pancreatic cancer (PC). Initiated trials include investigator-initiated trials (CT041-CG4006, NCT03874897), a confirmatory Phase II clinical trial for advanced G/GEJA in China (CT041-ST-01, NCT04581473), a Phase Ib registrational trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), an investigator-initiated trial for satri-cel be used as consolidation treatment following adjuvant therapy in patients with resected G/GEJA (CT041-CG4010, NCT06857786), an investigator-initiated trial for satri-cel as a sequential therapy following first-line treatment in patients with advanced G/GEJA (CT041-CG4011, NCT07179484), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595).

The Center for Drug Evaluation (CDE) of National Medical Products Administration (NMPA) of China has accepted the New Drug Application (NDA) for satri-cel for the treatment of Claudin18.2-positive advanced G/GEJA in patients who have failed at least two prior lines of therapy on June 25, 2025. It has been granted Priority Review in May 2025 and Breakthrough Therapy Designation in March 2025 by the CDE. Satri-cel was granted Regenerative Medicine Advanced Therapy designation by U.S. FDA for the treatment of advanced G/GEJA with Claudin18.2-positive tumors in January 2022. Satri-cel received Orphan Drug designation from the U.S. FDA for the treatment of G/GEJA in September 2020.

(Press release, Carsgen Therapeutics, OCT 19, 2025, View Source [SID1234656790])

On October 19, 2025 Pfizer Inc. (NYSE: PFE) and Astellas Pharma U.S. Inc. (Head of Commercial: Mike Petroutsas, "Astellas") reported final overall survival (OS) results from the Phase 3 EMBARK study evaluating XTANDI (enzalutamide), in combination with leuprolide and as monotherapy, in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as nonmetastatic castration-sensitive prostate cancer or nmCSPC) with biochemical recurrence (BCR) at high risk for metastasis. For the key secondary endpoint of OS, XTANDI plus leuprolide reduced the risk of death by 40.3% compared to leuprolide alone (Hazard Ratio [HR]: 0.597; 95% Confidence Interval [CI], 0.444-0.804; p=0.0006), making this the first and only androgen receptor inhibitor-based regimen to demonstrate an OS benefit in nmHSPC with high-risk BCR.1 The 8-year overall survival was 78.9% (95% CI, 73.9% to 83.1%) among patients receiving XTANDI plus leuprolide and 69.5% (95% CI, 64.0% to 74.3%) among patients taking leuprolide alone.1 A numerical improvement in OS with XTANDI as monotherapy compared to leuprolide alone (HR: 0.83 [95% CI, 0.63-1.095; p=0.1867) did not reach statistical significance.1 These data are being presented today in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Berlin, Germany and have been simultaneously published in The New England Journal of Medicine.

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"These results highlight the central role of enzalutamide in extending survival for men with conventional imaging negative HSPC with high-risk BCR," said Stephen J. Freedland, M.D., Director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai and Associate Director for Training and Education at the Samuel Oschin Comprehensive Cancer Institute. "These data reinforce the benefits of earlier treatment initiation with enzalutamide."

The median follow up time was 94.2 months for XTANDI in combination with leuprolide, 94 months for leuprolide only, and 93.8 months in the monotherapy XTANDI group.1

The safety profile of XTANDI was consistent with that observed at the primary EMBARK analysis, and no new safety signals were identified. The most common adverse events (occurring in ≥10% of patients) in the XTANDI combination group were hot flashes and fatigue. The most common adverse events in the XTANDI monotherapy group were gynecomastia, hot flashes, and fatigue.1,2

"With up to 90 percent of men with high-risk BCR developing metastatic disease, early intervention with effective therapy is critical,"3 said Johanna Bendell, M.D., Chief Development Officer, Oncology, Pfizer. "The final analysis from EMBARK shows that XTANDI plus leuprolide improved outcomes and extended lives for men facing high-risk BCR after local therapy with curative intent."

Among men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy or both, an estimated 20-40% will experience BCR within 10 years.4 About nine out of 10 men with high-risk BCR will develop metastatic disease, and one in three will die as a result of their metastatic prostate cancer.3

"This marks the eighth publication of XTANDI data in The New England Journal of Medicine, further demonstrating XTANDI’s profound impact on clinical outcomes in men with certain types of advanced prostate cancer," said Shontelle Dodson, Executive Vice President, Head of Medical Affairs, Astellas. "These findings reinforce XTANDI’s position as a cornerstone therapy in the proactive management of these patients."

The EMBARK trial primary analysis was previously reported in The New England Journal of Medicine in 2023, demonstrating that the study met its primary endpoint with a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) for patients treated with XTANDI plus leuprolide versus leuprolide alone (HR: 0.42 [95% CI, 0.30-0.61]; p<0.001). Additionally, MFS for XTANDI monotherapy was superior to treatment with leuprolide alone (HR: 0.63 [95% CI, 0.46-0.87]; p=0.005). Of note, the MFS for XTANDI single agent was a secondary endpoint.2

XTANDI is approved for one or more indications in more than 80 countries, including the United States, European Union, and Japan. Earlier approvals were for castration-resistant prostate cancer and metastatic castration-sensitive (hormone-sensitive) prostate cancer. It was then approved for patients with nmCSPC with BCR at high risk for metastasis in 2023 based on improved metastasis-free survival comparing the combination of enzalutamide with leuprolide vs leuprolide alone, as well as enzalutamide monotherapy vs leuprolide alone.

Descriptive updates of multiple secondary and exploratory endpoints (time to new antineoplastic therapy, time to first symptomatic skeletal events, and time to progression on subsequent therapy) were consistent with the primary analyses announced based on the MFS data cutoff in 2023.1

About EMBARK2

This Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,068 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR) at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region. Patients considered to have high-risk BCR disease had a prostate-specific antigen (PSA) doubling time ≤ 9 months, serum testosterone ≥ 150 ng/dL (5.2 nmol/L), and screening PSA by the central laboratory ≥ 1 ng/mL if they had had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer. Patients in the EMBARK trial were randomized to receive enzalutamide 160 mg daily plus leuprolide, enzalutamide 160 mg as monotherapy, or leuprolide alone.

The primary results from the EMBARK trial were published in the New England Journal of Medicine in 2023. The primary endpoint of the trial was metastasis-free survival (MFS) for enzalutamide plus leuprolide versus leuprolide alone. MFS is defined as the duration of time between randomization and the earliest objective evidence of radiographic progression by central imaging or death.

For more information on the EMBARK (NCT02319837) trial go to www.clinicaltrials.gov.

About Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence

Non-metastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) means there is no detectable evidence of the cancer spreading to distant parts of the body (metastases) with conventional radiological methods (CT/MRI) and the cancer still responds to medical or surgical treatment to lower testosterone levels.5,6 Of men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience a biochemical recurrence (BCR) within 10 years.4 About nine out of 10 men with high-risk BCR will develop metastatic disease, and one in three will die as a result of the recurrence.3 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC with high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA doubling time ≤ 9 months. Patients with nmCSPC who experience BCR after local therapy may be at a higher risk of metastases and death if their PSA doubling time is ≤ 9 months.7

About XTANDI (enzalutamide)

XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence (BCR). XTANDI is currently approved for one or more of these indications in more than 80 countries, including in the United States, European Union and Japan. Over 1.5 million patients have been treated with XTANDI globally.8

About XTANDI (enzalutamide) and U.S. Important Safety Information

XTANDI (enzalutamide) is indicated for the treatment of patients with:

castration-resistant prostate cancer (CRPC)
metastatic castration-sensitive prostate cancer (mCSPC)
nonmetastatic castration sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
Important Safety Information

Warnings and Precautions

Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Dysphagia or Choking Severe dysphagia or choking, including events that could be life-threatening requiring medical intervention or fatal, can occur due to XTANDI product size. Advise patients to take each capsule or tablet whole with a sufficient amount of water to ensure that all medication is successfully swallowed. Consider use of a smaller tablet size of XTANDI in patients who have difficulty swallowing. Discontinue XTANDI for patients who cannot swallow capsules or tablets.

Adverse Reactions (ARs)

In the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In EMBARK, the placebo-controlled study of nonmetastatic CSPC (nmCSPC) with high-risk biochemical recurrence (BCR) patients, Grade 3 or higher adverse reactions during the total duration of treatment were reported in 46% of patients treated with XTANDI plus leuprolide, 50% of patients receiving XTANDI as a single agent, and 43% of patients receiving placebo plus leuprolide. Permanent treatment discontinuation due to adverse reactions during the total duration of treatment as the primary reason was reported in 21% of patients treated with XTANDI plus leuprolide, 18% of patients receiving XTANDI as a single agent, and 10% of patients receiving placebo plus leuprolide.

Lab Abnormalities: Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hypophosphatemia, and hypercalcemia.

Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI. Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.

Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.

(Press release, Pfizer, OCT 19, 2025, View Source [SID1234656806])

On October 18, 2025 NuCana plc (NASDAQ: NCNA) ("NuCana" or the "Company") reported data at the European Society for Medical Oncology Congress 2025 ("ESMO") on a new model system investigating the synergistic effects of NUC-7738 and PD-1 inhibition in primary organoids derived from patients with renal cell carcinoma ("RCC").

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Using patient-derived organoids ("PDOs") from ten patients with RCC and autologous tumor-infiltrating lymphocytes ("TILs"), co-culture experiments reveal that NUC-7738 enhances the effectiveness of PD-1 inhibitors, resulting in increased tumor cell killing. This combinatorial approach may offer a new option for cancers that no longer respond to anti-PD-1 therapy by targeting multiple aspects of the tumor microenvironment through the disruption of RNA polyadenylation and subsequent changes in cancer cell gene expression.

The data presented at ESMO (Free ESMO Whitepaper) reinforces the mechanism of action for NUC-7738 as observed in the ongoing Phase 1/2 NuTide:701 clinical study. Data to date from NuTide:701 have demonstrated a favorable safety profile, meaningful tumor volume reduction, and prolonged progression-free survival in patients with PD-1 inhibitor refractory and resistant metastatic melanoma.

Andrew Kay, NuCana’s Executive Chairman said: "We are excited to share these new data on NUC-7738 in combination with PD-1 inhibitors in a real-time organoid model system. In addition to demonstrating clear benefits of combining PD-1 inhibitors with NUC-7738, similar to those seen in patients on the ongoing NuTide:701 study, this may lead to robust, patient-specific testing for a selection of immune checkpoint therapies."

Mr. Kay continued: "The translational data that has been generated in this study increases our confidence that the effects we are seeing are a result of NUC-7738 targeting multiple aspects of the tumor microenvironment and increasing PD-1 inhibition. Our data on mechanism of action of NUC-7738 indicate that the phenomena are not restricted to a single tumor type, and that NUC-7738 may have the ability to sensitize many cancers to PD-1 inhibitor therapy."

Based on the exciting initial data from the Phase 1/2 NuTide:701 clinical study, regulators have approved the expansion of the study to recruit an additional 28 patients with PD-1 inhibitor-resistant melanoma. NuCana is currently recruiting patients to this expansion study and plans to meet with the U.S. Food and Drug Administration to discuss the data from this study to determine the optimal registration strategy to support marketing approval.

The details of NuCana’s presentation at ESMO (Free ESMO Whitepaper) are as follows:

Abstract Title: Patient Derived Organoids Reveal Synergy Between NUC-7738 and PD-1 Inhibition in Renal Cell Cancer
Poster Number: 1530P
Session: Investigational Immunotherapy
Date: Sunday, October 19, 2025
Presenting Author: H. Abdullah

(Press release, Nucana, OCT 18, 2025, View Source [SID1234656774])

On October 18, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported results from a subgroup analysis of the CABINET phase 3 pivotal trial evaluating CABOMETYX (cabozantinib) versus placebo in patients with previously treated advanced neuroendocrine tumors (NET) originating in the lungs or thymus. These data will be presented at the 2025 European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) during the Monday Poster Session: Neuroendocrine Tumours on October 20, 2025, from 12:00 – 12:45 p.m. CEST.

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"The regulatory approvals of cabozantinib in the United States and European Union earlier this year provide a much-needed targeted treatment option for patients with previously treated advanced NET," said Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. "These subgroup results showing that cabozantinib achieved a meaningful progression-free survival benefit in patients with lung or thymic NET are encouraging, as these subtypes of the disease can be particularly challenging to treat."

In the phase 3 CABINET study, patients with locally advanced or metastatic pancreatic NET (pNET) or extra-pancreatic NET (epNET) were randomized 2:1 in separate cohorts to receive CABOMETYX 60 mg daily versus placebo. Patients with epNET had tumors arising in the gastrointestinal (GI) tract, lung, rare sites including the thymus and unknown primary sites. Of the 203 patients in the epNET cohort, 49 had lung or thymic NET. With a median follow-up for progression-free survival (PFS) of 5.5 months, CABOMETYX reduced the risk of disease progression or death by 81% versus placebo (stratified hazard ratio: 0.19; 95% confidence interval: 0.06-0.54; one-sided stratified log-rank P=0.0003). Median PFS was 8.2 months with CABOMETYX compared to 2.7 months with placebo. Confirmed objective response rates were 6% versus 0%, respectively.

"These subgroup data build upon the strong overall findings from the CABINET trial and reinforce the benefits of CABOMETYX for a heterogeneous NET patient population," said Dana T. Aftab, Ph.D., Executive Vice President, Research & Development, Exelixis. "Lung and thymic NET are forms of cancer with limited treatment options, and we are pleased CABOMETYX helps address an unmet need for these patients. We are committed to continuing to serve the NET patient community with our ongoing STELLAR-311 pivotal trial examining zanzalintinib as a potential first-line oral targeted therapy versus everolimus for patients with locally advanced or metastatic NET."

The safety profile of CABOMETYX observed in patients with lung or thymic NET was consistent with its known safety profile; no new safety signals were identified. The most frequent grade 3/4 adverse events attributed to CABOMETYX included fatigue (24%), hypertension (18%), diarrhea (9%) and palmar plantar erythrodysesthesia (9%).

In March 2025, the U.S. Food and Drug Administration approved CABOMETYX for the treatment of 1) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET; and 2) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated epNET, based on results from the CABINET study. In July 2025, the European Commission approved CABOMETYX for the treatment of adult patients with unresectable or metastatic, well-differentiated pNET and epNET who have progressed following at least one prior systemic therapy other than somatostatin analogues.

About CABINET (Alliance A021602)

CABINET (Randomized, Double-Blinded, Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network, as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.

CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that enrolled a total of 298 patients in two separate cohorts (pNET and epNET) in the U.S. at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo; each cohort was randomized separately and had its own statistical analysis plan. The trial was stopped early after an interim analysis showed superior efficacy associated with cabozantinib as compared to placebo in each of the two cohorts. Patients with epNET had primary tumors arising in the GI tract, lung, unknown primary sites and other organs. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior systemic therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial is available at ClinicalTrials.gov.

About NET

NET are cancers that begin in the specialized cells of the body’s neuroendocrine system.2 These cells have traits of both hormone-producing endocrine cells and nerve cells.2 It is estimated that 161,000 to 192,000 people in the U.S. are living with unresectable, locally advanced or metastatic NET.3 The number of people diagnosed with NET has been increasing in recent decades.4 Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing, while symptoms of non-functional NET are related primarily to tumor growth.5, 6, 7, 8, 9 Most NET take years to develop and grow slowly, but eventually all patients with advanced or metastatic NET will develop refractory and progressing disease.10, 11

NET can start in the pancreas (pNET), where they tend to be more aggressive, with a five-year survival rate of only 19% for advanced disease.2,12 NET can also develop in any part of the body, but most commonly start in the GI tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET.2 The five-year survival rate for advanced GI NET is 68%.13 For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, molecular targeted therapy and peptide-receptor radionuclide therapy.14

Approximately 2,000-4,500 people will be newly diagnosed with lung NET in the U.S. each year.15 The five-year survival rate for advanced lung NET is 49%.16 Thymic NET are rare, typically aggressive tumors with a worse prognosis compared to that of lung NET.17

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible; for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET; and adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated epNET. CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the EU. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in 1% of CABOMETYX patients. Monitor for signs and symptoms, and discontinue CABOMETYX in patients with Grade 4 fistulas or GI perforation.

Thrombotic Events: CABOMETYX can cause arterial or venous thromboembolic event. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. In CABINET (n=195), hypertension occurred in 65% (26% Grade 3) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with antihypertensive therapy or for hypertensive crisis.

Diarrhea: CABOMETYX can cause diarrhea and it occurred in 62% (10% Grade 3) of treated patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1; resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in 45% of treated patients (13% Grade 3). Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Monitor liver enzymes before initiation of treatment and periodically. Consider more frequent monitoring as compared to when the drugs are administered as single agents. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <1% of treated patients. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution; resume at a reduced dose.

Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in 19% of treated patients (0.4% Grade 3). Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in 13% of CABOMETYX patients (2% Grade 3 and 1% Grade 4).

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong or Moderate CYP3A4 Inducers: If coadministration with strong or moderate CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.

Please see accompanying full Prescribing Information View Source

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

(Press release, Exelixis, OCT 18, 2025, View Source [SID1234656744])