On September 29, 2025 Novocure (NASDAQ: NVCR) reported that final results from the Phase 3 METIS trial of Tumor Treating Fields (TTFields) therapy for brain metastases from non-small cell lung cancer (NSCLC) will be presented today at the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting taking place September 27 – October 1 in San Francisco and simultaneously published in the International Journal of Radiation Oncology Biology and Physics (Red Journal) (Press release, NovoCure, SEP 29, 2025, View Source [SID1234656330]).

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"Lung cancer patients with brain metastases are living longer due to improved systemic therapies, bringing to the forefront an unmet need for well-tolerated treatment options that provide more durable control of brain metastases," said Vinai Gondi, MD, Director of Radiation Oncology in the Northwestern Medicine West Region and Proton Center, Clinical Associate Professor of Radiation Oncology at Northwestern University Feinberg School of Medicine. "The METIS trial, demonstrating that the addition of Tumor Treating Fields following stereotactic radiosurgery delays brain metastasis progression with no negative impact on quality of life or neurocognition, is a pivotal and practice-impacting step forward in providing patients with a new treatment option."

The METIS trial evaluated the use of TTFields therapy and best supportive care (BSC) to treat adult patients with 1-10 newly diagnosed brain metastases from NSCLC following stereotactic radiosurgery (SRS) compared to BSC alone. The trial met its primary endpoint, showing a statistically significant delay in time to first intracranial progression for patients who received TTFields therapy and BSC compared to patients receiving BSC alone.

"One of the challenges in treating patients with primary lung cancer is the high incidence of brain metastases in this population. When Tumor Treating Fields therapy was used to treat patients in the METIS trial, we saw a significant delay in the progression of intracranial metastases without adding systemic toxicity or causing neurocognitive side effects associated with other current treatments," said Nicolas Leupin, MD, PhD, Chief Medical Officer, Novocure. "We plan to submit our premarket approval application to the FDA for the treatment of adult patients with brain metastases from non-small cell lung cancer in the coming weeks."

Results from Pivotal Phase 3 METIS Trial

The pivotal Phase 3 METIS trial enrolled 298 adult patients with 1-10 brain metastases from NSCLC, who were randomized to receive either TTFields therapy and BSC (n=149) or BSC alone (n=149) following SRS of their brain metastases. Systemic anti-cancer therapy was allowed to treat the primary disease.

The primary endpoint of the METIS trial was defined as the time to intracranial progression (TTIP), as measured from the date of first SRS treatment to intracranial progression or neurological death, whichever occurred first.

When accounting for competing risks using the Fine–Gray method, patients treated with TTFields therapy and BSC experienced a 28% lower risk of intracranial progression compared to those receiving BSC alone (HR 0.72, p=0.044). The median time to intracranial progression was 15.0 months in patients treated with TTFields therapy and BSC compared to 7.5 months in patients treated with BSC alone.

Intracranial progression rates in both groups were measured at specific time points up to 24 months. At 2 months, those patients treated with TTFields therapy and BSC had a 13.6% progression rate compared to 22.1% (p=0.034) in those treated with BSC alone. At 6 months a 33.7% progression rate compared to 46.4% (p=0.018) was observed; at 12 months a 46.9% progression rate compared to 59.4% (p=0.023) was observed and at 24 months the rate was 53.6% compared to 65.2% (p=0.031; post hoc), in those patients treated with TTFields therapy and BSC compared to those treated with BSC alone, respectively.

There was no significant difference observed in the secondary endpoint measures of neurocognitive failure, overall survival or radiological response of brain lesions (measured with MRI).

Time to distant intracranial progression (TTDP) trended in favor of TTFields therapy with a median time to distant progression of 18.6 months for patients treated with TTFields therapy and BSC, and 11.3 months in the BSC alone arm, HR 0.76, p=0.165.

In the 118 patients in the TTFields group who received immune checkpoint inhibitors (ICI) for their primary disease during their participation in the METIS study, the beneficial effects observed on TTIP and TTDP were more pronounced, HR=0.63 and HR=0.41, post hoc, respectively.

TTFields therapy did not cause quality of life deterioration overall in the measured outcomes. Improvements in deterioration-free survival and time to deterioration of the global health status, physical functioning and fatigue domains were observed in patients treated with TTFields therapy.

Median duration of TTFields therapy was 16 weeks and median usage was 67%. Baseline patient demographics and characteristics were well balanced across the arms of the study.

The safety profile of TTFields therapy was consistent with that seen in other clinical trials. Grade 1/2 skin issues were the most common device-related adverse events and subcutaneous tissue events.

Data Presentation & Publication Details

The Phase 3 METIS data, (LBA 03) Tumor Treating Fields (TTFields) After Stereotactic Radiosurgery (SRS) for Brain Metastases from Non-Small Cell Lung Cancer (NSCLC BM): Final Results of The Phase 3 METIS Trial, will be presented by Dr. Gondi September 29 during the 1:30 – 3:00 PM PT Plenary session in the San Francisco Ballroom at the Moscone Center.

The Phase 3 METIS publication in the International Journal of Radiation Oncology Biology and Physics (Red Journal), "Tumor Treating Fields (TTFields) therapy after stereotactic radiosurgery for brain metastases from non-small cell lung cancer: final results of the phase 3 METIS study", will be available online at www.redjournal.org.

About Tumor Treating Fields

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. These multiple, distinct mechanisms work together to target and kill cancer cells. Due to these multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors.

To learn more about TTFields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On September 29, 2025 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported updates on the company’s Phase 2 clinical program evaluating JK07 in heart failure with reduced ejection fraction (HFrEF), heart failure with preserved (HFpEF) and Group 2 pulmonary hypertension (PH), as well as its Phase 1 clinical study of JK06 in solid tumor indications (Press release, Salubris Biotherapeutics, SEP 29, 2025, View Source [SID1234656329]).

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"We are thrilled to have two clinical-stage programs both progressing and expanding in development. Importantly, we have now completed enrollment for the HFrEF cohort in the ongoing Phase 2 RENEU-HF study, putting us on track for a topline readout of the primary endpoint in the first half of 2026. We continue to believe that JK07, the first and only clinical-stage selective ErbB4 agonist, has the potential to be the first disease-modifying biologic for heart failure, and we very much look forward to these results. We are also pleased to announce that we have initiated the open-label Phase 2a RENEU-PH study evaluating JK07 in patients with combined pre- and post-capillary Group 2 pulmonary hypertension due to heart failure, a population with no approved treatment options and a poor prognosis. JK07’s potential to target both myocardial dysfunction and the pulmonary vasculature may provide a unique dual benefit in this population," said Sam Murphy, Chief Executive Officer of SalubrisBio.

"We are also eagerly anticipating the European Society for Medical Oncology Congress next month, where we will present initial data from our ongoing first-in-human study evaluating JK06, our novel, first-in-class biparatopic antibody-drug conjugate (ADC) targeting 5T4, and are excited to now be moving into the expansion cohort stage of the study."

JK07 Phase 2 (RENEU-HF) Study

RENEU-HF (NCT06369298) is a global Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study designed to evaluate the efficacy and safety of JK07 in patients with HFrEF and HFpEF in 282 subjects. The study has two cohorts: cohort 1, which has completed enrollment, is comprised of patients with HFrEF; cohort 2 is currently enrolling patients with HFpEF. The primary endpoint of the study for the HFrEF cohort is change in left ventricular ejection fraction (LVEF) at 26 weeks. The HFrEF cohort enrolled 215 subjects, randomized 1:1:1 to high or low dose JK07 or placebo. Results of the primary endpoint analysis are expected in the first half of 2026.

Heart failure affects an estimated 6.7 million Americans1 and more than 64 million people worldwide2, with HFrEF and HFpEF each affecting over 3 million patients in the US alone. HF is a chronic condition in which patients experience progressively worsening symptoms and quality of life, hospitalizations and death. In HFrEF, the left ventricle loses its ability to contract normally, and the heart cannot pump with sufficient force to push enough blood into circulation. In HFpEF the heart becomes stiff and loses its ability to function properly.

JK07 Phase 2a (RENEU-PH) Study
The Phase 2a, open-label, multiple-dose study is designed to evaluate the safety, efficacy, and tolerability of JK07 in patients with combined pre- and post-capillary Group 2 pulmonary hypertension (cpcPH) due to HF. This 6-month study is expected to enroll up to 30 patients who will receive four every-4-week (QW4) doses of JK07, over the course of 13 weeks, with a 12-week follow-up period.

Chronic pulmonary hypertension (PH) due to left heart disease represents a significant complication in patients with HF. Epidemiologic studies suggest that up to 50% of patients with HFrEF or HFpEF exhibit some degree of PH, and cpcPH is associated with markedly worse outcomes, including increased hospitalizations and mortality3.

JK06 Phase 1 Study
The ongoing Phase 1, open-label, dose escalation and expansion study (EUCT2024-512421-92-00) is designed to assess the safety, pharmacokinetics, and preliminary efficacy of JK06 in a basket of solid tumors known to express the protein 5T4, with a target enrollment of up to 155 patients. Enrollment has now been completed in the dose escalation phase of the study, and initial data will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress taking place on October 17-21, 2025, in Berlin, Germany. Details of the presentation are as follows:

Title: A Phase 1/2 Study of JK06, a 5T4-Targeted Antibody Drug Conjugate (ADC), in Patients with Unresectable Locally Advanced or Metastatic Cancer
Presenter: Nuria Kotecki, M.D. at Institut Jules Bordet, Anderlecht, Belgium
Abstract #: 961P
Session: Developmental Therapeutics
Date/Time: Sunday, October 19, 2025

About JK07
JK07 is a recombinant antibody fusion protein consisting of an active polypeptide fragment of the human growth factor neuregulin (NRG-1) and a fully human immunoglobulin IgG1 monoclonal antibody targeting ErbB3. NRG-1 is a clinically validated growth factor that has shown promising activity in HF, but also undesirable side effects. Research has shown that NRG-1 induces signaling through interaction with two different receptors – ErbB3 and ErbB4. The ErbB4 pathway appears to be responsible for the regenerative effects in the heart, while the ErbB3 pathway appears primarily responsible for the safety and tolerability limitations of recombinant NRG-1. By blocking ErbB3 signaling with an antibody fusion design, JK07 selectively stimulates the ErbB4 pathway with a favorable pharmacokinetic profile, which has the potential to significantly widen the therapeutic window of NRG-1 and yield better clinical effects. JK07 is in clinical development for the treatment of HFrEF, HFpEF, and cpcPH.

About JK06
JK06 is a first-in-class quadrivalent, biparatopic antibody drug conjugate (ADC) that selectively targets 5T4 with a monomethyl auristatin E (MMAE) payload. 5T4 is an oncofetal protein that is overexpressed in a wide range of tumor types, including lung and breast cancers, and is associated with more aggressive tumor progression and reduced survival. JK06 has demonstrated picomolar affinity for 5T4 and rapid internalization due to the biparatopic design. Together with stable, site-specific payload conjugation, JK06 has further demonstrated robust efficacy and a clean safety profile in non-clinical studies.

On September 29, 2025 Children’s Hospital of Philadelphia (CHOP) reported that Theodore W. Laetsch, MD, a pediatric oncologist and principal investigator in the Advanced Personalized Therapeutics and Precision Surgery Program, was awarded a $1 million multi-year grant from the National Cancer Institute (NCI) (Press release, CHOP, SEP 29, 2025, View Source [SID1234656328]). The grant will advance research and treatment of rare tumors, which are responsible for 25% of cancer-related deaths.

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Historically understudied, rare tumors have seen less improvement in outcomes compared to more common cancers due to numerous obstacles in clinical research. Additionally, most rare pediatric cancers occur in the adolescent and young adult population, where treatment is often dispersed across various subspecialties.

The grant supports Laetsch’s commitment to tackling these challenges and advancing the understanding and precision medicine approach to treating rare tumors across the Children’s Oncology Group (COG), within CHOP, at the University of Pennsylvania, and in mentoring junior investigators. Laetsch, who also leads CHOP’s Developmental Therapeutics Program and Very Rare Malignant Tumors Program, and holds national leadership roles within COG, has been instrumental in addressing myriad challenges facing the field. These include the limited availability of biospecimens, small patient numbers, and the complexity of designing novel clinical trials.

"This grant represents a pivotal milestone in our quest to transform rare tumor research and enhance patient outcomes," said Laetsch. "Our mission is to bridge gaps in clinical research and ensure that children and adolescents have access to cutting-edge precision treatment options."

The grant will allow Laetsch and his team to focus on immunotherapy trials and molecularly targeted therapies for rare cancers. This initiative will oversee the development of novel studies for patients never previously researched within COG, such as those with thyroid cancer and melanoma.

The funding will also help establish the Advanced Personalized Therapeutics and Precision Surgery Program, a pediatric-adult rare tumor program at the Leonard and Madlyn Abramson Pediatric Research Center. The program aims to increase enrollment in both the National Clinical Trials Network (NCTN) and investigator-initiated precision medicine trials for children and adults with rare tumors and help physicians find appropriate trials for their patients.

The grant is expected to expand the pipeline of rare tumor clinical trials within the NCTN. It will boost participation in NCI-funded rare tumor clinical research across all age groups at the Abramson Cancer Center and enhance both institutional and COG biobanks.

Dr. Laetsch will also mentor the next generation of clinicians specializing in rare tumors and developmental therapeutics. Through the COG/NCTN, he will guide young researchers in designing and leading future studies.

"The award underscores the importance of fostering new talent in the field and ensuring a sustained focus on rare tumor research," said Laetsch.

On September 29, 2025 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical-stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported subgroup analyses focused on the radiation regimen from the Company’s positive phase 3 clinical trial of CAN-2409 (aglatimagene besadenovec) in patients with intermediate-to-high-risk localized prostate cancer at the 2025 Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Press release, Candel Therapeutics, SEP 29, 2025, View Source [SID1234656327]).

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Current standard-of-care radiation therapy for intermediate-to-high-risk localized prostate cancer has remained largely unchanged, with a significant unmet medical need, as approximately ~30% of patients experience disease recurrence within 10 years.

The Company has previously presented data from a randomized phase 3 clinical trial of CAN-2409 plus valacyclovir vs. placebo added to standard of care radiotherapy with curative intent in patients with localized prostate cancer. The press release is posted on the investor relations section of our website, available here. The randomized, double-blind, placebo-controlled, multicenter phase 3 trial (NCT01436968) enrolled 745 patients with intermediate-to-high-risk localized prostate cancer randomized 2:1 to either CAN-2409 plus valacyclovir in combination with standard of care or standard of care alone, with experimental treatment administered before and during radiation therapy. The trial achieved its primary endpoint with a 30% improvement in disease-free survival (HR 0.7, p=0.0155) and demonstrated a 38% improvement in prostate cancer-specific disease-free survival (HR 0.62, p=0.0046). At two years, pathological complete response rates were 80.4% as compared to 63.6% observed in the control arm (p=0.0015).

This study represents the first potential advancement in localized, non-metastatic prostate cancer in more than 20 years. The Company today released additional information from its subgroup analysis of the phase 3 data showing that CAN-2409’s activity was independent of the radiation modality used in the trial.

Key Highlights from ASTRO 2025 Presentation:

CAN-2409 significantly improved prostate cancer-specific outcomes (HR 0.62; p=0.0046). Effects observed in both moderate hypofractionated EBRT (HR 0.52, CI 0.30 – 0.93, p=0.0236) and conventional EBRT (HR 0.76, CI 0.53 – 1.07, p=0.1131)
Demonstrated safety and compatibility across radiation therapy modalities, with both conventional radiation therapy (~78 Gy in 2 Gy fractions, ~72% of patients) and moderate hypofractionated radiation therapy (60 Gy in 3 Gy fractions, ~25% of patients) showing similar tolerability profiles
Grade ≥ 3 treatment related adverse events were similar in the CAN-2409 plus valacyclovir and control arms with both hypofractionated (1.6% vs. 1.9%) and standard EBRT (1.8% vs. 1.1%), respectively
"These additional analyses suggest that the efficacy of CAN-2409 is independent of the modality of radiation used. Most importantly, the activity of CAN-2409 was maintained with moderate hypofractionated radiation, which is more convenient for patients," said Glen Gejerman, M.D., M.B.A., Co-Director of Urologic Oncology at Hackensack Meridian Health and one of the principal investigators of the study.

Paul Peter Tak, M.D., Ph.D., FMedSci, President and Chief Executive Officer of Candel said, "These new insights presented at ASTRO further support the broad therapeutic potential of CAN-2409 in localized prostate cancer treated with curative intent. Previously, we have shown the benefit of CAN-2409 compared to placebo in patients treated with standard of care radiotherapy, independent of the use of short-term androgen deprivation therapy. The consistency of benefit, across radiation therapy modalities, supports the therapy’s potential as the first major advancement in localized prostate cancer treatment in over 20 years. Our regulatory strategy remains on track with Biologics License Application submission expected in the fourth quarter of 2026."

About CAN-2409

CAN-2409 (aglatimagene besadenovec), Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s tumor. After intratumoral administration, HSV-tk enzyme activity results in conversion of prodrug (valacyclovir) into deoxyribonucleic acid (DNA)-incorporating nucleotide analogs, leading to immunogenic cell death in cells exhibiting DNA damage and proliferating cells, with subsequent release of a variety of tumor (neo)antigens in the tumor microenvironment. At the same time, the adenoviral serotype 5 capsid proteins promote inflammation through the induction of expression of pro-inflammatory cytokines, chemokines, and adhesion molecules. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ immunization against a variety of tumor antigens. CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed with CAN-2409 in clinical trials with a favorable tolerability profile to date, supporting the potential for combination with standard of care, when indicated.

On September 29, 2025 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported that the US Patent and Trademark Office (USPTO) has notified the Company that a key patent protecting the Company’s best-in-class FAK inhibitor narmafotinib has been allowed in the US (Press release, Amplia Therapeutics, SEP 29, 2025, View Source [SID1234656325]). The patent, titled A salt and crystal form of a FAK Inhibitor, describes the specific chemical form of narmafotinib being utilised in currently ongoing clinical trials.

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The patent allowance precedes a formal ‘Notification of Grant’ of the patent, which is expected in the coming months. The Company has previously announced that this key patent has already been granted in Japan and Europe1, and it has also been granted in Australia, India, Korea, Singapore, and New Zealand. Granting of this patent extends protection of narmafotinib out to a least 2040 in these jurisdictions. Protection in other regions is under review by the respective patent offices.

This patent describes a stable, manufacturable form of narmafotinib that provides improved drug levels upon dosing. Importantly, it is this specific form of the drug that is being developed clinically by the Company, including in the current ACCENT and AMPLICITY trials in advanced pancreatic cancer.

Amplia’s CEO and Managing Director Dr Chris Burns comments: "We continue to build a patent portfolio around narmafotinib to ensure the Company’s key intellectual property is protected and thus commercially valuable, for as long as possible."