On February 28, 2026 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Eisai reported the first presentation of results from the Phase 3 LITESPARK-011 trial evaluating the dual oral regimen of WELIREG (belzutifan), Merck’s first-in-class oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, plus LENVIMA (lenvatinib), an orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease progressed on or after treatment with anti-programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy. These data are being presented as a late-breaking oral abstract at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium (abstract #LBA417) and are included in the official ASCO (Free ASCO Whitepaper) GU Press Program.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At a pre-specified interim analysis with a median follow-up of 29.0 months (range, 19.3-49.2), WELIREG plus LENVIMA demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS), reducing the risk of disease progression or death by 30% (HR=0.70 [95% CI, 0.59-0.84]; p=0.00007) compared to cabozantinib. For WELIREG plus LENVIMA, the median PFS was 14.8 months (95% CI, 11.2-16.6) versus 10.7 months (95% CI, 9.2-11.1) for cabozantinib. A trend toward improvement in overall survival (OS), the trial’s other primary endpoint, was also observed for WELIREG plus LENVIMA (HR=0.85 [95% CI, 0.68-1.05]; p=0.06075). The median OS was 34.9 months (95% CI, 27.5-NR) for WELIREG plus LENVIMA versus 27.6 months (95% CI, 24.0-31.4) for cabozantinib. The trial is continuing, and OS will be evaluated at a subsequent analysis per the clinical trial protocol.

Based on data from the LITESPARK-011 trial, the U.S. Food and Drug Administration (FDA) has accepted two supplemental New Drug Applications (sNDA) for review seeking approval for WELIREG plus LENVIMA for the treatment of adult patients with advanced RCC with a clear cell component following a PD-1 or PD-L1 inhibitor. The FDA set a Prescription Drug User Fee Act (PDUFA), or target action date, of October 4, 2026 for both the WELIREG and LENVIMA sNDAs. Merck and Eisai will also discuss these data with regulatory authorities worldwide to support potential submissions outside the United States.

"Choosing the right treatment for patients with advanced renal cell carcinoma after immunotherapy has been an ongoing challenge, and treatment options in this setting had not previously been evaluated against a current standard of care tyrosine kinase inhibitor in a Phase 3 trial," said Dr. Robert Motzer, Principal Investigator and Genitourinary Medical Oncologist, Memorial Sloan Kettering Cancer Center. "The LITESPARK-011 study demonstrated a 30% reduction in the risk of disease progression or death with belzutifan plus lenvatinib compared to cabozantinib, and 52.6% of patients experienced a response to treatment. These findings mark a critical step forward for these patients."

"The LITESPARK-011 trial highlights the potential of this first-of-its-kind combination regimen to deliver a meaningful benefit for patients with advanced renal cell carcinoma whose disease progresses after PD-1/L1 therapy," said Dr. M. Catherine Pietanza, Vice President, Global Clinical Development, Merck Research Laboratories. "These WELIREG plus LENVIMA data demonstrate important progress for patients with advanced renal cell carcinoma and reinforce our commitment to improving the lives of patients through innovative treatment strategies."

"The LITESPARK-011 results reinforce LENVIMA’s established role in renal cell carcinoma and highlight the potential of this novel combination to address an area of significant unmet need," said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai. "The acceptance of this regulatory filing is an important milestone, and we remain committed to working toward approval to bring this option to patients as soon as possible. We are grateful to the patients, their families, and the investigators, whose dedication made this research possible."

Additional findings

Data for objective response rate (ORR) and duration of response (DOR), two key secondary endpoints, were also reported. At the first interim analysis with a median follow-up of 19.6 months (range, 9.9-39.8), WELIREG plus LENVIMA met ORR, demonstrating a statistically significant improvement compared to cabozantinib. A confirmed ORR of 52.6% (95% CI, 47.3-57.7) was observed for WELIREG plus LENVIMA versus 39.6% (95% CI, 34.6-44.8) for cabozantinib. At the second interim analysis with a median follow-up of 29.0 months, the median DOR was 23.0 months (95% CI, 2.0-44.3+) for WELIREG plus LENVIMA versus 12.3 months (95% CI, 1.8+-35.9+) for cabozantinib.

WELIREG plus LENVIMA was administered to 370 patients and cabozantinib was administered to 371 patients. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 71.6% of patients receiving WELIREG plus LENVIMA versus 65.8% of patients receiving cabozantinib. Adverse events led to the discontinuation of 11.1% of patients receiving WELIREG plus LENVIMA versus 11.3% of patients receiving cabozantinib, respectively. Serious adverse events were observed in 51.6% of patients receiving WELIREG plus LENVIMA versus 43.9% of patients receiving cabozantinib, and AEs led to death in 5.4% of patients (two were treatment-related: thrombotic microangiopathy [n=1] and pneumonitis [n=1]) versus 3.2% (one was treatment-related: hemoptysis [n=1]) of patients, respectively.

LITESPARK-011 is part of a comprehensive late-stage clinical development program for WELIREG comprised of several Phase 2 and Phase 3 trials in pheochromocytoma and paraganglioma, von Hippel-Lindau disease-associated neoplasms and RCC.

The Phase 3 LITESPARK-012 trial is evaluating the addition of WELIREG to KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, plus LENVIMA in the first-line advanced RCC disease setting.

WELIREG is approved in the U.S., European Union (EU), Japan and other countries for the treatment of adult patients with advanced clear cell RCC following a PD-1/PD-L1 inhibitor and 1-2 VEGF-TKIs based on results from the Phase 3 LITESPARK-005 trial.

KEYTRUDA plus LENVIMA is approved in the U.S., the EU, Japan and other countries for the treatment of advanced RCC. Lenvatinib is approved as KISPLYX for advanced RCC in the EU.

LENVIMA in combination with everolimus is approved in the U.S., EU and other regions for the treatment of adult patients with advanced RCC following one prior anti-angiogenic therapy.

Dr. Motzer has provided consulting and advisory services for Merck and Eisai.

About LITESPARK-011

LITESPARK-011 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT04586231) evaluating WELIREG in combination with LENVIMA compared to cabozantinib for the treatment of patients with advanced clear cell RCC that has progressed on or after anti-PD-1/L1 therapy. The dual primary endpoints are PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include ORR per RECIST v1.1 as assessed by BICR, DOR per RECIST v1.1 as assessed by BICR, and safety. The trial enrolled 747 patients who were randomized to receive WELIREG (120 mg orally once daily) plus LENVIMA (20 mg orally once daily) or cabozantinib (60 mg orally once daily).

About renal cell carcinoma

Renal cell carcinoma is the most common type of kidney cancer, with about nine out of 10 kidney cancer diagnoses being RCC. In 2022, there were about 435,000 new cases of kidney cancer and approximately 156,000 deaths from the disease worldwide. RCC is about twice as common in men as in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Approximately 30% of patients with kidney cancer are diagnosed at an advanced stage.

(Press release, Merck & Co, FEB 28, 2026, View Source [SID1234663143])

On February 27, 2026, the U.S. Food and Drug Administration ("FDA") reported a Complete Response Letter ("CRL") for the supplemental Biologics License Application ("sBLA") for Zynyz (retifanlimab-dlwr) injection (375mg) for an additional indication for the treatment of adult patients with metastatic non-small cell lung cancer ("NSCLC") in combination with platinum-based chemotherapy. The sBLA was supported by positive efficacy and safety data from the Phase 3 POD1UM-304 trial announced in December 2024.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The CRL cited inspection findings (not specific to Zynyz) at Catalent Indiana, LLC ("Catalent Indiana"), part of Novo Nordisk, the third-party fill-finish facility referenced in the sBLA. The CRL cited the regulatory compliance of Catalent Indiana as the sole approvability issue, and did not cite other approvability concerns, including Zynyz’s efficacy and safety data in NSCLC or the third-party drug substance manufacturer.

Incyte Corporation is working closely with the FDA and Catalent Indiana to address the CRL and support a potential sBLA resubmission of Zynyz in NSCLC.

(Press release, Incyte, FEB 27, 2026, View Source [SID1234663336])

On February 27, 2026 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), a publicly traded biotechnology and precision intracellular drug-delivery company, reported the launch of a private placement (the "Private Placement") of up to 20,000,000 units (the "Units") at a price of $0.55 per Unit, for aggregate gross proceeds to Defence of up to $11,000,000. Each Unit will be comprised of one common share (each, a "Share") and one common share purchase warrant ("Warrants"). Each Warrant will entitle its holder to acquire an additional common share of the Company at a price of $0.65 per share for 24 months following the date of issuance.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company has executed a binding term sheet with two arm’s length institutional investors (collectively, the "Investors") in connection with the Private Placement for aggregate gross proceeds of $6,000,000 (CAD) (the "Investors’ Proceeds"). In connection with the Private Placement, the Investors’ Proceeds and the Units will be deposited in escrow in advance of closing pursuant to an escrow agreement (the "Escrow Agreement"). Upon closing, the Units will be released from escrow and delivered to the Investors or as they may direct, and the Investors’ Proceeds will be released from escrow and deposited as credit support pursuant to an ISDA Credit Support Annex, and released to the Company in monthly cash tranches of $333,333 (CAD) over an 18-month period (the "Term"), pursuant to the terms and conditions of a sharing agreement (the "Sharing Agreement") to be dated and executed on the closing of the Private Placement. Settlements under the Sharing Agreement shall commence five months after closing.

Pursuant to the Sharing Agreement, Shares will be released in equal monthly installments of approximately 606,060 Shares over the 18-month Term, with each release contingent upon the corresponding cash payment being delivered to the Company. The Sharing Agreement shall provide that the Company’s economic interest will be determined in 18 monthly settlement tranches as measured against a benchmark price of $0.7332 (CAD) per Share (the "Benchmark Price"). If, at the time of settlement, the settlement price (determined monthly based on a 20-day volume-weighted average trading price of the Company’s shares on the CSE) exceeds the Benchmark Price, the Company shall receive more than 100% of the monthly settlement due, on a pro rata basis, with no upper limit on additional proceeds. If the settlement price is below the Benchmark Price, the Company will receive less than 100% of the monthly settlement due, on a pro rata basis. In no event will a decline in the settlement price result in an increase in the number of Shares being issued to the Investors. As a result, the Company may ultimately receive more or materially less than the original proceeds of $6,000,000. The final amount received will depend on the Company’s future share price, which is subject to market fluctuations and may vary over time. Accordingly, there is no assurance as to the total amount the Company will receive under the Sharing Agreement.

All 10,909,091 Warrants to be issued shall be exercisable at an exercise price of $0.65 (CAD) per Share for a period of 24 months following the date of issuance. The Warrants will include an equity blocker provision that prohibits the holder from exercising any portion of the Warrants if such exercise would result in the holder owning more than 9.99% of the Company’s outstanding Shares.

The Investors will receive a corporate finance fee of $360,000 (CAD) in connection with the Sharing Agreement, payable in cash or via the issuance of 654,546 Units at the Private Placement price, at the election of the Company (the "Fee").

The Company has agreed to pay a non-refundable deposit of $65,000 (CAD)
(the "Deposit") upon receipt of approval from the CSE in connection with the Private Placement. The Deposit shall be satisfied by the issuance of 118,182 Units at the Private Placement price.

Defence intends to use the proceeds from the Private Placement to advance its Antibody Drug Conjugate ("ADC") and Radiopharmaceutical programs, to develop partnerships and for working capital purposes. The Company may pay a finder’s fee in connection with the offering to eligible arm’s-length finders in accordance with the policies of the Canadian Securities Exchanges.

Pursuant to applicable Canadian securities laws and in accordance with the Exchange policies, all securities issued under this Private Placement will be subject to applicable resale restrictions under applicable securities laws. The closing of the Private Placement is expected on or about March 6, 2026, subject to the approval of the CSE.

The Units described herein have not been, and will not be, registered under the U.S. Securities Act or any state securities laws, and accordingly, may not be offered or sold within the United States except in compliance with the registration requirements of the U.S. Securities Act and applicable state securities requirements or pursuant to exemptions there from. This press release does not constitute an offer to sell or a solicitation to buy any securities in any jurisdiction.

(Press release, Defence Therapeutics, FEB 27, 2026, View Source;utm_medium=rss&utm_campaign=defence-therapeutics-announces-private-placement-of-units-for-proceeds-of-up-to-11-million [SID1234663221])

On February 27, 2026 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, reported it will present new data in genitourinary malignancies at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU), taking place February 26-28, 2026.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Across four oral presentations in muscle-invasive bladder cancer (MIBC), these data reinforce Signatera’s role in identifying patients who benefit from adjuvant immunotherapy, supporting response-adaptive bladder preservation strategies, and refining molecular residual disease (MRD) detection with plasma circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA).

Bladder Preservation: INDIBLADE and RETAIN

The INDIBLADE and RETAIN multicenter phase 2 trials demonstrate Signatera’s consistent performance in treatment response monitoring across diverse neoadjuvant regimens in MIBC, with 73-77% of patients demonstrating clearance of ctDNA following therapy and Signatera-negativity showing strong associations with positive outcomes, even with the bladder preserved.

INDIBLADE, the findings of which will be published today in Nature Medicine, investigated induction with combination immune checkpoint inhibitors (ICI) followed by chemoradiotherapy as a bladder-sparing strategy in stage II/III MIBC patients. The results show that Signatera status post-ICI was associated with bladder-intact event-free survival (BI-EFS). Specifically, Signatera-negativity at baseline and post-neoadjuvant therapy was linked to an 88.6% and 91% estimated two-year BI-EFS, respectively.

RETAIN evaluated a clinical response-adapted approach to identify patients for potential bladder-preservation following neoadjuvant therapy. The findings showed that post-treatment ctDNA clearance or negativity was associated with improved metastasis-free survival (MFS), and that Signatera-negative patients with no clinical or radiographic evidence of disease managed with active surveillance achieved MFS comparable to Signatera-negative patients undergoing cystectomy. In contrast, persistent Signatera-positivity was associated with poor outcomes.

Perioperative Care: NIAGARA

This phase 3 randomized perioperative study includes the first-ever presentation of utDNA data with clinical correlation. The combination of utDNA and ctDNA status post-neoadjuvant therapy and pre-cystectomy identified the group with the highest 24-month EFS. utDNA-positivity pre-cystectomy was more strongly associated with residual non-invasive disease vs ctDNA-positivity was more strongly associated with residual invasive disease. These data suggest that the combined assessment of utDNA and ctDNA can provide complementary risk stratification benchmarked against pathologic staging, enabling comprehensive identification of residual disease.

"As treatment options expand in perioperative and bladder preservation settings, we need tools that help us determine who truly requires additional therapy and who may safely avoid it," said Michiel van der Heijden, M.D., Ph.D., Netherlands Cancer Institute, principal investigator of INDIBLADE and presenting author of the NIAGARA study. "The data presented at ASCO (Free ASCO Whitepaper) GU demonstrate that MRD assessment with Signatera has strong correlations with outcomes and the potential to inform these critical treatment decisions."

"Following our milestone PMA submission to the FDA based on IMvigor011, these compelling data presentations reflect our commitment to transforming care across the spectrum of genitourinary malignancies," said Minetta Liu, M.D., chief medical officer of oncology and early cancer detection at Natera. "The new data suggests a particularly important opportunity for Signatera to optimize clinical decisions around bladder preservation, a major opening to improve patient quality of life."

The full list of presentations at ASCO (Free ASCO Whitepaper) GU includes:

February 27, 8:10 AM PT | Abstract #633 (Oral Presentation)
Presenter: Joaquim Bellmunt, M.D.
Circulating tumor (ct)DNA-guided adjuvant atezolizumab (atezo) in muscle-invasive bladder cancer (MIBC): Exploratory analysis of ctDNA dynamics in the IMvigor011 trial

February 27, 8:10 AM PT | Abstract #632 (Oral Presentation)
Presenter: Pooja Ghatalia, M.D.
Circulating tumor DNA (ctDNA) to guide response-adapted bladder preservation in muscle invasive bladder cancer (MIBC): Integrated analysis of the RETAIN trials

February 27, 11:30 AM PT | Abstract #797
Presenter: Can Aydogdu, M.D.
Integrating genomic profiling and circulating tumor DNA monitoring to optimize surveillance strategies in muscle-invasive bladder cancer

February 27, 11:30 AM PT | Abstract #831
Presenter: Can Aydogdu, M.D.
Association of ctDNA status with upstaging, pathologic outcomes, and genomic alterations in high-risk NMIBC

February 27, 2:30 PM PT | Abstract #637 (Oral Presentation)
Presenter: Jan-Jaap J. Mellema, M.D.
Induction ipilimumab plus nivolumab followed by consolidating chemoradiotherapy as bladder-sparing treatment in stage II/III urothelial carcinoma of the bladder: The phase 2 INDIBLADE trial

February 27, 4:00 PM PT | Abstract #636 (Oral Presentation)
Presenter: Michiel van der Heijden, M.D., Ph.D.
Urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) in patients (pts) with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA

February 28, 7:00 AM PT | Abstract #532
Presenter: Shuchi Gulati, M.D., M.Sc.
Association of pre-operative circulating tumor DNA (ctDNA) status with clinicopathologic characteristics in patients (pts) with localized renal cell carcinoma (RCC)

February 28, 7:00 AM PT | Abstract #620
Presenter: Dalia Kaakour, M.D., MPH
Use of circulating tumor DNA (ctDNA) in the detection of residual disease and recurrence for patients with testicular cancer

February 27, 11:30 AM PT | Abstract #860
Presenter: Lingbin Meng, M.D., Ph.D.
Use of circulating tumor DNA (ctDNA) in the detection of residual disease and recurrence for patients with testicular cancer

February 27, 11:30 AM PT | Abstract #800
Presenter: Tanya Jindal, BS, BA
Predictive value of early circulating tumor DNA (ctDNA) response in advanced urothelial carcinoma (aUC) treated with enfortumab vedotin plus pembrolizumab (EVP).

February 28, 7:00 AM PT | Abstract #541
Presenter: David F. McDermott, M.D.
Circulating tumor DNA (ctDNA) analysis in participants (pts) with advanced clear cell renal cell carcinoma (ccRCC) treated with first-line pembrolizumab (pembro) monotherapy from the phase 2 KEYNOTE-427 study.

(Press release, Natera, FEB 27, 2026, View Source [SID1234663139])

On February 27, 2026 Bayer reported results from the ongoing global Phase I first-in-human, dose-escalation PAnTHa study (NCT06217822) evaluating the safety, tolerability and preliminary efficacy of 225Ac-PSMA-Trillium (BAY 3563254), a next-generation targeted alpha therapy (TAT) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). The dose for expansion was successfully identified, with ≥80% of patients achieving a PSA50 response at the expansion dose.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

New data were presented during the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium, taking place in San Francisco, CA, United States, from February 26-28, 2026. These clinical data represent the first disclosure for 225Ac-PSMA-Trillium and were selected as part of the rapid oral session focused on advanced prostate cancer research. They support advancing 225Ac-PSMA-Trillium to the next phase of clinical development. TAT is a strategic pillar of precision oncology at Bayer, with the potential to accelerate novel treatment options for patients with mCRPC.

"We are excited to see the results from the Phase I PAnTHa study demonstrating the potential of our next-generation targeted alpha therapy to provide new treatment options for patients with advanced metastatic castration-resistant prostate cancer (mCRPC), a type of cancer with limited treatment options and poor prognosis," said Dominik Ruettinger, M.D., Ph.D., Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division. "The development of 225Ac-PSMA-Trillium confirms our ongoing focus on prostate cancer treatment and continued drive to develop precise and personalized healthcare solutions."

"Despite progress, patients with metastatic castration-resistant prostate cancer continue to face high mortality, highlighting the urgent need for new precision therapies," said Fred Saad, MD, FRCS, Professor and Chairman of Surgery at the University of Montreal and Director of Genitourinary Oncology at the University of Montreal Hospital Center (CHUM), Canada. "The promising data support the further investigation of this molecule to provide a potentially meaningful clinical benefit for patients with mCRPC."

225Ac-PSMA-Trillium (BAY 3563254) is a next-generation investigational TAT labeled with actinium-225 and comprising a novel PSMA (prostate-specific membrane antigen)-targeting small molecule with a customized albumin-binding moiety. The compound is designed specifically to increase uptake within the tumor, with the goal to provide a differentiated safety and efficacy profile.

Prostate cancer is the second most commonly diagnosed cancer in men with less than three years median survival among metastatic patients, who have developed castration-resistance. There is an increasing unmet need to improve the outcomes of men with mCRPC.6

About the PAnTHa study (NCT06217822)
PSMA-targeted Actinium-225-Trillium FiH study in Advanced mCRPC (PAnTHa), is a Phase I, open-label, first-in-human, multicenter study to evaluate safety, tolerability, pharmacokinetics, and antitumor activity of 225Ac-PSMA-Trillium (BAY 3563254) in participants with advanced metastatic castration resistant prostate cancer (mCRPC) that have at least 1 PSMA-positive lesion on PSMA-PET. In the trial, patients received 225Ac-PSMA-Trillium intravenously every 6 weeks for up to 4 doses. At data cut-off, 50 patients were enrolled across four dose levels in the escalation cohort and 80% completed all four cycles of 225Ac-PSMA-Trillium (range: 75 to 150 kBq/kg; 12-13 patients/cohort).

Detailed Results from PAnTHa
To date, 225Ac-PSMA-Trillium has had no dose-limiting toxicities (DLTs) or treatment-related deaths. Most common treatment-emergent adverse events (TEAEs) were dry mouth, fatigue and nausea. Overall, 38% of patients had Gr ≥3 TEAEs, most commonly lymphopenia, 16% of patients had serious TEAEs and 4% of patients discontinued treatment due to TEAEs. The overall response rate per PCWG3 criteria across all doses in patients with measurable disease at baseline (n=24) was 46%, with disease control rate of 83%. Respective PSA50 and PSA90 response rates were 58% and 36% overall, and 83% and 58% at the Recommended Dose for Expansion (RDE). This was further supported by the decline in circulating tumor DNA (ctDNA) fraction at the RDE. Further, PSA50 responses were observed across all baseline mean Standardized Uptake Value (SUVmean) groups.

About 225Ac-PSMA-Trillium (BAY 3563254)
225Ac-PSMA-Trillium (BAY 3563254) is a next-generation TAT that comprises a highly specific PSMA-targeting motif, an albumin-binding domain to optimize tumor uptake and retention, and a MacropaTM chelator complexed with the alpha-emitter actinium-225. The distinctive structural components are designed to provide a differentiated safety and efficacy profile. Both in vitro and in vivo characterization of 225Ac-PSMA-Trillium demonstrates high tumor uptake and retention. Potent antitumor efficacy has been observed in several preclinical models of prostate cancer. PSMA-Trillium resulted from the acquisition of PSMA Therapeutics and Noria Therapeutics in 2021 and are now under clinical investigation.

About Targeted Alpha Therapy
Targeted alpha therapy (TAT) is an emerging class of radionuclide therapy that can be used against a variety of tumors. It delivers alpha particle radiation directly to the tumor inside the body, either via its bone-seeking property (radium-223) or by combining alpha radionuclides, such as actinium-225, with specific targeting moieties.

Actinium-225 is an alpha particle–emitting radionuclide with a 9.9-day half-life. Alpha particles deposit highly ionizing radiation over a short range. This localized delivery of the radioactive payload induces irreparable DNA double-strand breaks, often resulting in cell death.

About prostate cancer
Prostate cancer is the second most commonly diagnosed cancer in men. Despite significant advances in the last decade, the prognosis for men with mCRPC remains poor with a median survival of about 31 months.2 With increasing incidence, more than 300 thousand prostate cancer cases were reported in the US in 2025; 5-year relative survival with distant disease is only 34%.3 Advances in imaging technologies (i.e. PSMA-PET) and their utilization across all stages of prostate cancer will likely result in an increased number of patients diagnosed with metastatic disease earlier. Consequently, more men will be diagnosed with de novo PSMA-positive metastatic disease.

(Press release, Bayer, FEB 27, 2026, View Source [SID1234663138])