On October 1, 2025 Ensem Therapeutics, Inc. (ENSEM) reported the U.S. Food and Drug Administration (FDA) granted Fast Track designation to its clinical stage pan mutant-specific allosteric PI3Kα inhibitor and degrader, ETX-636, for the treatment of adult patients with PIK3CA-mutant, hormone receptor positive (HR+)/human epidermal growth factor negative (HER2-) advanced breast cancer (Press release, ENSEM Therapeutics, OCT 1, 2025, View Source [SID1234656387]).

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ETX-636 was designed using ENSEM’s unique Kinetic Ensemble platform to optimally fit into a specific allosteric binding site in p110α, the catalytic subunit of PI3Kα and can selectively inhibit multiple activating mutant forms of PI3Kα, while sparing wildtype PI3Kα. The selectivity of ETX-636 for mutant PI3Kα greatly reduces the risk for hyperglycemia and other wildtype PI3Kα-related adverse events compared to non-mutant selective PI3Kα inhibitors. In addition, ETX-636 also leads to proteasome-dependent degradation of mutant PI3Kα, while sparing wildtype protein (a feature not seen with other pan-mutant allosteric inhibitors).

Activating mutations or alterations of the PI3Kα pathway are known to promote cancer cell growth and survival in a variety of tumor types, including breast cancer. In HR+/HER2- breast cancer (approximately 70% of all breast cancers), PIK3CA mutations are particularly prevalent, occurring in up to 40% of the cases.

"Patients with advanced HR+/HER2- breast cancer harboring PIK3CA mutations have poor prognosis, and there is an unmet need for therapies targeting this population that are safer and more efficacious than the current FDA approved non-mutant selective treatments," said Dr. Shengfang Jin, CEO and Co-Founder of ENSEM. "We are appreciative that the FDA has recognized ETX-636 as a potentially important treatment for this indication and we remain laser-focused on demonstrating its benefit to patients in our current clinical trials."

ETX-636 is currently being studied in an initial first-in-human, Phase 1/2 study which is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ETX-636 in participants with advanced solid tumors harboring a PIK3CA mutation. ETX-636 will be administered alone or in combination with fulvestrant, a selective estrogen receptor degrader approved for the treatment of advanced hormone receptor HR+/HER2- breast cancer NCT06993844.

Fast Track designation is a program provided by the FDA to expedite the development and review of drugs and biologics that treat serious conditions with unmet medical needs. It provides the opportunity for frequent and early communication and collaboration with the FDA, as well as the potential for accelerated approval and priority review eligibility to allow faster access to promising treatment to patients.

On October 1, 2025 NUCLIDIUM AG, a clinical-stage radiopharmaceutical company developing a proprietary copper-based theranostic platform, reported that it has received a Notice of Allowance from the U.S. Patent and Trademark Office (USPTO) for a patent covering the company’s KaliosTM-program (Press release, NUCLIDIUM, OCT 1, 2025, https://nuclidium.com/nuclidium-receives-notice-of-allowance-for-composition-of-matter-patent-covering-fap-inhibitor-based-radiodiagnostics-and-therapeutics-in-the-united-states/ [SID1234656372]). Once issued, the composition-of-matter patent will protect a variety of small molecule inhibitors of the fibroblast activation protein (FAP) that can be used in combination with a range of radionuclides bound with a variety of chelating moieties for the diagnosis and treatment of diseases, including solid tumors. The KaliosTM-program consists of a tumor-targeting FAP inhibitor labelled with a pre-selected copper radioisotope: Copper-61 for diagnostics and Copper-67 for therapeutics. The program is currently in development for the diagnosis and treatment of certain breast and lung cancer indications.

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"The Notice of Allowance from the U.S. Patent and Trademark Office is an important milestone for NUCLIDIUM as we continue to advance our best-in-class copper-based radiotheranostics. This initial action from the U.S. Patent office strengthens our intellectual property position in a highly competitive field. It also recognizes the innovation inherent in our approach and supports our long-term goal of addressing unmet needs in oncology, especially in women’s health, through innovative copper-based radiopharmaceuticals. We are committed to building a robust patent portfolio that protects our discoveries and to advancing our copper-based theranostics into clinical evaluation," said Leila Jaafar, PhD, CEO and Co-Founder of NUCLIDIUM.

The expected patent covers a diverse range of inhibitors that target FAP, representing broad protection for Nuclidium’s current and future radiopharmaceuticals and theranostics in its KaliosTM-program. FAP is a membrane-bound serine protease (dipeptidyl peptidase) present in epithelial tumors that make up 80-90% of all cancer cases. It is highly expressed on cancer-associated fibroblasts in the tumor stroma as well as in degenerative tissues or inflamed tissues such as bursitis and fibrosis. These characteristics render FAP an attractive target for cancer diagnosis and treatment. Currently approved FAP-targeted radioligands, labelled with either 68Ga or 18F, have a short half-life, which restricts their ability for delayed imaging to identify and treat smaller metastases and, in addition, limits their possible distribution range after production.

Nuclidium and its collaborators recently published a preclinical study in the European Journal of Nuclear Medicine and Molecular Imaging – Radiopharmacy and Chemistry, highlighting the unique potential of copper-based FAP-targeting PET radiotracers. In the study, [61Cu]Cu-Kalios PET radioligands showed favorable pharmacokinetics, high tumor uptake, and strong tumor-to-background ratios with delayed 4h imaging when compared to established FAP-targeting radiotracers. These findings underscore the clinical potential of 61-copper-based radiopharmaceuticals to improve the temporal imaging range for precise detection of FAP-expressing tumors.

On October 1, 2025 MiraDx, a molecular diagnostics company focused on genetic testing to personalize cancer treatment, reported that its PROSTOX ultra test is now available for ordering in the United States (Press release, MiraDx, OCT 1, 2025, View Source [SID1234656388]). The test, which helps identify localized prostate cancer patients at increased risk of developing side effects from stereotactic body radiation therapy (SBRT), has already helped over 3,500 patients as part of an Early Access Program involving select academic centers and private practices.

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PROSTOX ultra is a clinically validated genetic test that identifies patients with localized prostate cancer at higher risk of developing late genitourinary toxicity—urinary side effects such as urgency, leakage, or discomfort that may occur after treatment—with SBRT. SBRT delivers high doses of radiation over a short period of time, typically within 5-7 treatments. While SBRT is effective for treatment of prostate cancer, a subset of patients experience these side effects that present months or even years after treatment and can persist. By identifying patients with increased sensitivity to SBRT, PROSTOX ultra helps doctors and patients make more informed treatment decisions and consider alternative options when needed.

"Initial data from the PROSTOX Early Access Program in patients identified as having a high risk of toxicity to SBRT found that results from the test changed the course of treatment for 77% of these patients, helping them avoid potential complications from SBRT," said Melissa Stoppler, MD, Executive Vice President of Medical Affairs at MiraDx. "Extending access to this test to a broader range of clinicians and clinical settings will enable more prostate cancer patients to benefit from testing for these novel biomarkers of toxicity to radiation treatments."

PROSTOX ultra is a new and innovative test, and as such, coverage may vary depending on insurance plans. To ensure access, MiraDx is offering a Financial Assistance Program for patients, which provides reduced pricing based on household income.

On October 1, 2025 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that it will present ten abstracts from our portfolio and advancing pipeline at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress taking place from 17-21 October 2025, including new data for PADCEV (enfortumab vedotin) plus pembrolizumab in muscle-invasive bladder cancer (MIBC) which will be presented in an ESMO (Free ESMO Whitepaper) Presidential Symposium on 18 October (Press release, Astellas, OCT 1, 2025, View Source [SID1234656373]). In prostate cancer, we are sharing final best-in-class overall survival data for XTANDI (enzalutamide) in high-risk, biochemically recurrent non-metastatic hormone sensitive disease, plus encouraging data for our next-generation bispecific T cell engager ASP2138 in solid tumors, demonstrating continued leadership in CLDN18.2-targeted precision medicine.

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Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Head of Oncology Development, Astellas
"Astellas focuses on some of the most complex and devastating cancers. These ESMO (Free ESMO Whitepaper) data demonstrate our ‘bench to bedside’ approach in action – from deep disease biology to measurable improvements in patient outcomes. We’re proud to share breakthrough new survival data in muscle-invasive bladder cancer and overall survival data in hormone sensitive prostate cancer, which reflect potentially practice-changing advances that could transform outcomes for patients who need them most. We also continue to advance innovation in gastric and gastroesophageal junction cancer with new clinical data for our next-generation investigational bispecific T cell engager."

Highlights from Astellas at ESMO (Free ESMO Whitepaper) 2025 will include:

Data from the Phase 3 EV-303 (also known as KEYNOTE-905) clinical trial which will be featured in an ESMO (Free ESMO Whitepaper) Presidential Symposium, evaluating enfortumab vedotin in combination with pembrolizumab as neoadjuvant and adjuvant treatment (before and after surgery) versus surgery alone, the current standard of care, in patients with MIBC who are not eligible for or declined cisplatin-based chemotherapy.
Long-term follow-up data from the EV-302 clinical trial exploring the utility of enfortumab vedotin in combination with pembrolizumab for patients with challenging baseline characteristics, including older patients with locally advanced or metastatic urothelial cancer and those with comorbidities such as diabetes and chronic kidney disease.
Final data from the Phase 3 EMBARK trial assessing overall survival with enzalutamide in combination with leuprolide and as monotherapy in 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.
First clinical data from Astellas’ investigational CLDN18.2-targeted, next-generation bispecific CD3 T cell engager ASP2138, both as a monotherapy and in combination with standard of care therapy.
Astellas Presentations at ESMO (Free ESMO Whitepaper) Congress 2025

Enfortumab vedotin

Presentation Title

Presenter

Presentation Details

Perioperative enfortumab vedotin plus pembrolizumab in participants with muscle-invasive bladder cancer who are cisplatin-ineligible: The phase 3 KEYNOTE-905 study

C. Vulsteke

Type: Presidential Symposium 1

Abstract Number: LBA2

Date: October 18,
16:52 – 17:04 CEST

Enfortumab vedotin and pembrolizumab in previously untreated locally advanced or metastatic urothelial cancer: An exploratory analysis in older patients and those with comorbidities from EV-302

N. Mar

Type: Poster

Abstract Number: 3073P

Date: October 18,
12:00-12:45 CEST

Enfortumab vedotin plus pembrolizumab as first-line treatment in recurrent or metastatic head and neck squamous cell carcinoma: Results from a cohort of the EV-202 trial

P.L. Swiecicki

Type: Mini oral

Abstract Number: 1329 MO

Date: October 19,
17:38-17:43 CEST

EV-103 Cohort K: Efficacy and safety of enfortumab vedotin with or without pembrolizumab in cisplatin-ineligible pts with previously untreated locally advanced or metastatic urothelial cancer with a median follow-up of ≈3.5 y

T.W. Friedlander

Type: Poster

Abstract Number: 3074P

Date: October 18,
12:00-12:45 CEST

Real-world use of enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer previously treated with chemotherapy and immunotherapy in France

A. Fléchon

Type: ePoster

Abstract Number: 3111eP

Date: October 18, 12:00-12:45 CEST

Enzalutamide

Presentation Title

Presenter

Presentation Details

Overall survival in EMBARK, a phase 3 randomised trial of enzalutamide or placebo plus leuprolide and enzalutamide monotherapy in patients with nonmetastatic hormone-sensitive prostate cancer with biochemical recurrence at high risk for metastasis

S.J. Freedland

Type: Proffered Paper

Abstract Number: LBA87

Date: October 19,
10:55-11:05 CEST

Baseline features and metastasis-free survival by prior definitive treatment in patients with high-risk biochemically recurrent prostate cancer: EMBARK post hoc analysis

N.D. Shore

Type: Poster

Abstract Number: 2461P

Date: October 18,
12:00-12:45 CEST

Pipeline

Presentation Title

Presenter

Presentation Details

ASP2138 monotherapy in patients with (CLDN18.2)+, advanced solid tumors: Phase 1/1b trial

K. Shitara

Type: Poster

Abstract Number: 2137P

Date: October 19,
12:00-12:45 CEST

ASP2138 monotherapy or in combination with pembrolizumab and mFOLFOX6 or with ramucirumab and paclitaxel in (CLDN18.2)+ locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: Phase 1/1b trial

F. Dayyani

Type: Poster

Abstract Number: 2136P

Date: October 19,
12:00-12:45 CEST

Phase 1 trial of ASP5541 (PRL-02), a long-acting intramuscular depot injection of abiraterone decanoate, in patients with advanced prostate cancer

J. Avitia

Type: Poster

Abstract Number: 2443P

Date: October 18,
12:00-12:45 CEST

On October 1, 2025 KaliVir Immunotherapeutics, Inc., a clinical-stage biotechnology company developing cutting-edge, multi-mechanistic oncolytic immunotherapy programs, reported the successful completion of the first cohort in the intravenous (IV) infusion arm of its STEALTH-001 (NCT06444815) clinical study, a Phase 1/1b clinical trial of VET3-TGI for patients with incurable, advanced solid tumors (Press release, KaliVir Immunotherapeutics, OCT 1, 2025, View Source [SID1234656389]).

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Patients received VET3-TGI, the Company’s lead oncolytic immunotherapy candidate, which is designed to selectively kill tumor cells and remodel the tumor microenvironment by delivering a potent immuno-stimulatory transgene payload composed of interleukin-12 (IL-12) and a TGFbeta inhibitor.

"The dosing of patients in the IV arm marks a significant advancement for the STEALTH-001 study and the broader field of systemic oncolytic viral immunotherapy," said Dr. Yana Najjar, MD, Associate Professor in the Department of Medicine at the University of Pittsburgh and Director of the Clinical and Translational Research Center at UPMC Hillman Cancer Center. "Delivering VET3-TGI intravenously opens the door to using oncolytic virotherapy to treat patients with tumors that are not easily accessible for direct injection, expanding the potential reach of this therapeutic approach."

The continuation of IV dosing complements continued enrollment in the intratumoral (IT) arm of the Phase 1/1b trial, where patients are now being treated in cohort 3, and supports plans for combining VET3-TGI with checkpoint inhibitor therapy. The STEALTH-001 trial is evaluating VET3-TGI as both a monotherapy and in combination with a checkpoint inhibitor in patients with advanced, unresectable, or metastatic solid tumors.

"Systemic delivery of VET3-TGI is essential to realizing its full therapeutic potential, and this first IV dose brings us closer to that goal," said James Burke, MD, Chief Medical Officer of KaliVir Immunotherapeutics. "VET3-TGI was engineered to selectively infect tumor cells and deliver a potent combination of IL-12 and a TGFbeta inhibitor, stimulate a strong immune response and overcome tumor-driven immunosuppression. This milestone supports our broader goal of developing multi-mechanistic oncolytic immunotherapies that can address a wide range of solid tumors."

About VET3-TGI and the STEALTH-001 Study
VET3-TGI is a novel oncolytic virus developed using KaliVir’s proprietary VET platform. It is designed to selectively replicate in tumor cells, stimulate local immune responses, and remodel the immunosuppressive tumor microenvironment through the expression of IL-12 and a TGFβ inhibitor. The STEALTH-001 study is a first-in-human, open-label, dose escalation and expansion Phase 1/1b trial assessing both intratumoral and intravenous administration of VET3-TGI.VE

The STEALTH-001 trial is a dose escalation and expansion study evaluating VET3-TGI administered through direct IT injection and IV infusion. The trial is evaluating VET3-TGI as a monotherapy and in combination with a checkpoint inhibitor in patients with pathologically confirmed, advanced, unresectable or metastatic solid tumors. The study continues to progress as planned through its dose escalation phase.