On February 14, 2025 Remegen reported that Professor Xinan Sheng from Peking University Cancer Hospital delivered the latest efficacy and safety data from the phase II clinical trial (NCT05297552, Study ID: RC48-C017) of Disitamab Vedotin (DV) in combination Toripalimab as the neoadjuvant therapy for HER2-expressing muscle-invasive bladder cancer (MIBC) in an oral presentation at the ongoing 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) held in San Francisco, USA (Press release, RemeGen, FEB 14, 2025, View Source [SID1234650296]). This marks the first public disclosure of results from a prospective clinical study investigating an ADC drug in combination with an immunotherapy as a perioperative therapy for MIBC. The pathological complete response (pCR) rate reached an impressive 63.6%, which is a breakthrough improvement compared with traditional neoadjuvant chemotherapies (36%-42%). ASCO (Free ASCO Whitepaper) GU is one of the top urologic oncology conferences that leading experts worldwide in this field attend.

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The NCT05297552 study explored the synergy between the targeted therapy and immunotherapy in the perioperative setting for MIBC. Specifically, it assessed the safety and efficacy of the novel combination therapy featuring DV, a HER2-targeting ADC drug initially developed by RemeGen Co., Ltd. (RemeGen), and Toripalimab, a PD-1 inhibitor. In May 2024, based on the NCT05297552 study, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) granted breakthrough therapy designation to DV. The preliminary results of this study were presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting and led to widespread attention and discussion among experts worldwide. The updated data at ASCO (Free ASCO Whitepaper) GU further validated the clinical benefits of this therapeutic approach.

In the NCT05297552 study, 47 eligible patients (10.6% with HER2 IHC 1+, 57.4% with IHC 2+, and 31.9% with IHC 3+) received the investigational neoadjuvant therapy, among whom 33 patients underwent radical cystectomy and pelvic lymph node dissection (RC + PLND). As of the data cut-off date on December 3, 2024, the study demonstrated promising efficacy and manageable safety profiles:

The pathological complete response (pCR) rate reached an impressive 63.6% (95% CI: 45.1% – 79.6%), nearly doubling that observed with traditional neoadjuvant chemotherapies (36%-42%). The pathological response rate was 75.8% (95% CI: 57.7% – 88.9%). The study showed that for patients with baseline clinical stage of T2N0, the postoperative pCR rate reached 85.7%. A pCR rate of 55.6% was also achieved in patients with other pathological subtypes of urothelial carcinoma at baseline. Patients benefited significantly regardless of PD-L1 positive/negative and regardless of HER2 expression status (IHC 1+/2+/3+), among whom the pCR rate stood at 84.6% for HER2 IHC 3+ patients.
The 12-month event-free survival (EFS) rate of all patients who underwent radical cystectomy was 92.5%, and the 18-month EFS rate was 85.9%.

The therapy exhibited a manageable safety profile. The incidence of grade 3 or higher treatment-emergent adverse events (TEAEs) was only 27.7%, notably lower than the traditional chemotherapy regimen (40%-50%), suggesting a favorable tolerability.

RemeGen is advancing research on targeted and personalized therapies for bladder cancer through indication expansion and therapy innovation of DV, aiming to provide more potent treatment options for patients worldwide. Currently, studies are in-progress to explore the feasibility of expanding DV-based regimens from later-line to front-line treatment for locally advanced or metastatic urothelial cancer. There are also plans to broaden the research of DV as a neoadjuvant therapy for MIBC to the entire perioperative period and investigate the synergy between DV and chemotherapy or other immunotherapies in treating urothelial cancer.

On February 14, 2025 Astrazeneca reported results from a post-hoc exploratory subgroup analysis from the NIAGARA Phase III trial showed that Imfinzi (durvalumab), administered perioperatively in combination with neoadjuvant chemotherapy, demonstrated improvements in event-free survival (EFS) and overall survival (OS) versus neoadjuvant chemotherapy with radical cystectomy alone in patients with or without a pathologic complete response (pCR) in muscle-invasive bladder cancer (MIBC) (Press release, AstraZeneca, FEB 14, 2025, View Source [SID1234650295]). Patients were treated with four cycles of Imfinzi in combination with neoadjuvant chemotherapy before radical cystectomy (surgery to remove the bladder) followed by eight cycles of Imfinzi monotherapy.

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These new data were presented today at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in San Francisco, California (abstract #659).

In NIAGARA, treatment with the Imfinzi perioperative regimen improved EFS and OS versus the comparator arm both in patients who achieved pCR and those who did not. This regimen reduced the risk of disease progression, recurrence, not undergoing surgery, or death by 42% in patients who achieved pCR and by 23% in those who did not; and reduced the risk of death by 28% in patients who achieved pCR and by 16% in those who did not (see data table below for details).

The Imfinzi perioperative regimen also improved metastasis-free survival (MFS) and disease-specific survival (DSS), two secondary endpoints, versus the comparator arm in the intent-to-treat (ITT) population. This regimen reduced the risk of developing distant metastases or death by 33% and the risk of death specifically due to bladder cancer by 31% versus the comparator arm (see data table below for details).

Matthew ND. Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, and NIAGARA Investigator and Steering Committee member, said: "These NIAGARA data confirm the compelling efficacy of the durvalumab perioperative regimen in muscle-invasive bladder cancer, and importantly, show this regimen improved outcomes regardless of whether patients achieved a pathologic complete response. This insight, together with the data showing the durvalumab perioperative regimen extended the time patients live before distant metastases develop, is favourable news for patients with muscle-invasive bladder cancer who are in need of better treatment options."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "NIAGARA was the first Phase III trial of a perioperative immunotherapy regimen in muscle-invasive bladder cancer to show statistically significant and clinically meaningful improvements in event-free and overall survival. The 33 per cent reduction in the risk of distant metastases, which are associated with a poorer prognosis, further reinforces the potential of perioperative Imfinzi to become a new standard of care in this setting."

These new data build on findings presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in The New England Journal of Medicine which showed NIAGARA met the primary endpoint of EFS and the key secondary endpoint of OS. In the ITT population, patients treated with the Imfinzi perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm, as well as a 25% reduction in the risk of death. There was also a 10% improvement in the pCR rate versus the comparator arm.

Summary of exploratory post-hoc analysis: NIAGARA

Patients with pCR

Patients without pCR

ITT population

Imfinzi-based regimen

(n=199)

Neoadjuvant chemotherapy (n=146)

Imfinzi-based regimen

(n=334)

Neoadjuvant chemotherapy (n=384)

Imfinzi-based regimen

(n=533)

Neoadjuvant chemotherapy (n=530)

pCRi

pCR rate (%)

–

–

–

–

37.3

27.5

p-valueii

–

–

0.0005

EFSi

EFS rate, 24 months (%)

92.1

85.8

53.3

49.5

67.8

59.8

HR (95% CI)

0.58

(0.33-1.00)

0.77

(0.63-0.95)

0.68

(0.56-0.82)

OSi

OS rate, 24 months (%)

95.5

91.1

74.1

68.9

82.2

75.2

HR (95% CI)

0.72

(0.37-1.43)

0.84

(0.66-1.07)

0.75

(0.59-0.93)

i Data cut-off: 29 April 2024

ii Nominal p-value

Summary of additional secondary endpoint outcomes (ITT): NIAGARA

Imfinzi-based regimen

(n=533)

Neoadjuvant chemotherapy

(n=530)

MFSi

MFS rate, 24 months (%)

75.1

65.1

Number of MFS events (%)

152

(28.5)

201

(37.9)

Median MFS (95% CI) (in months)

NRii

(NRii-NRii)

NRii

(48.0-NRii)

HR (95% CI)

0.67

(0.54-0.83)

DSSi

DSS rate, 24 months (%)

89.2

82.2

Number of deaths due to bladder cancer (%)

85

(15.9)

114

(21.5)

Median DSS (95% CI) (in months)

NRii

(NRii-NRii)

NRii

(NRii-NRii)

HR (95% CI)

0.69

(0.52-0.91)

i Data cut-off: 29 April 2024

ii NR, not reached

Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events (imAEs) were consistent with the known profile of Imfinzi, manageable and mostly low-grade.

Perioperative Imfinzi in combination with neoadjuvant chemotherapy was granted Priority Review in the US in December 2024 for the treatment of patients with MIBC. Regulatory applications are also currently under review in the European Union (EU), Japan and several other countries based on the NIAGARA trial.

Notes

Muscle-invasive bladder cancer
Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year.1 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.2 Approximately one in four patients with bladder cancer has evidence of the tumour invading the muscle wall of the bladder (without distant metastases), known as MIBC.3-4

In MIBC, a curative-intent setting, approximately 117,000 patients are treated with the current standard of care, which includes neoadjuvant chemotherapy and radical cystectomy.5-6 However, even after cystectomy, approximately 50% of patients experience disease recurrence and have a poor prognosis.6 Treatment options that prevent disease recurrence after surgery are critically needed in this curative-intent setting.

NIAGARA
NIAGARA is a randomised, open-label, multi-centre, global Phase III trial evaluating perioperative Imfinzi as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomised to receive Imfinzi plus neoadjuvant chemotherapy prior to cystectomy followed by Imfinzi, or neoadjuvant chemotherapy alone prior to cystectomy with no further treatment after surgery. NIAGARA is the largest global Phase III trial in this setting.

The trial is being conducted at 192 centres across 22 countries including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS and pCR, the latter defined as the proportion of patients with no detectable cancer cells (T0N0M0) at the time of cystectomy. Key secondary endpoints are OS and safety.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.

In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

Imfinzi is also approved in combination with chemotherapy (carboplatin and paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) in the US. In the EU, Imfinzi plus chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer, and Imfinzi plus chemotherapy followed by Imfinzi alone is approved for patients with dMMR disease. In Japan, Imfinzi plus chemotherapy followed by Imfinzi monotherapy has also been approved as 1st-line treatment in primary advanced or recurrent endometrial cancer, and Imfinzi plus chemotherapy followed by Imfinzi and Lynparza has been approved for patients with pMMR disease.

Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours.

On February 14, 2025 Citius Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR), a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products reported business and financial results for the fiscal first quarter ended December 31, 2024 (Press release, Citius Pharmaceuticals, FEB 14, 2025, View Source [SID1234650293]).

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Fiscal First Quarter 2025 Business Highlights and Subsequent Developments

- Substantially advanced operational readiness for commercial launch of LYMPHIR in the first half of 2025;

- Secured a new permanent J-code, J9161, (Injection, denileukin diftitox-cxdl, for intravenous use, 1 microgram) for LYMPHIR, assigned by the Centers for Medicare & Medicaid Services (CMS), with an expected effective date of April 1, 2025;

- Announced promising preliminary results from an ongoing investigator-initiated Phase I clinical trial of a combined regimen of checkpoint inhibitor pembrolizumab and LYMPHIR (denileukin diftitox-cxdl) in patients with recurrent solid tumors. Presented data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting;

- Supported expansion of the University of Minnesota’s investigator-initiated Phase I clinical trial to evaluate the safety and efficacy of denileukin diftitox administration prior to Chimeric Antigen Receptor (CAR-T) therapies for the treatment of B-cell lymphomas with the dosing of the first patient at City of Hope cancer center;

- Engaged with the U.S. Food and Drug Administration (FDA) to clarify development paths for pipeline assets Mino-Lok and Halo-Lido;

- Advanced strategic and financing initiatives to help secure the capital needed to drive the full potential of our clinical and commercial programs.

o Citius Oncology (Nasdaq: CTOR), our majority-owned subsidiary, engaged Jefferies as exclusive financial advisor to assist in evaluating strategic alternatives aimed at maximizing shareholder value;

o Completed registered direct offerings of common stock and warrants in November 2024 and January 2025, and sold shares of common stock through the Company’s "at-the-market" facility in January 2025 for combined gross proceeds of $6.5 million;

o Effective November 25, 2024, the Company executed a reverse stock split of its common stock, at a ratio of 1-for-25; and,

- On December 18, 2024, the Company received notification that it had regained compliance with the $1.00 per share requirement for continued inclusion on the Nasdaq Stock Market.

Financial Highlights

- Cash and cash equivalents of $1.1 million as of December 31, 2024;

- R&D expenses were $2.1 million for the first quarter ended December 31, 2024, compared to $2.6 million for the first quarter ended December 31, 2023;

- G&A expenses were $5.4 million for the first quarter ended December 31, 2024, compared to $3.7 million for the first quarter ended December 31, 2023;

- Stock-based compensation expense was $2.5 million for the first quarter ended December 31, 2024, compared to $3.1 million for the first quarter ended December 31, 2023; and,

- Net loss was $10.3 million, or ($1.30) per share for the first quarter ended December 31, 2024, compared to a net loss of $9.2 million, or ($1.45) per share for the first quarter ended December 31, 2023.

"As we continue to advance our strategic priorities, we remain engaged in active discussions with potential partners who recognize the value of our pipeline and our commitment to developing innovative therapies for patients with high unmet medical needs. Securing the necessary financing to support our key programs remains a top priority, and we are evaluating multiple options to strengthen our financial position," stated Leonard Mazur, Chairman and CEO of Citius Pharmaceuticals.

"In parallel, we are making significant progress in our preparations for the anticipated launch of LYMPHIR in the first half of 2025, positioning us to bring this important therapy to patients while creating long-term value for our shareholders. We look forward to providing further updates as we execute on these critical initiatives," added Mazur.

FISCAL FIRST QUARTER 2025 Financial Results:

Liquidity

As of December 31, 2024, the Company had $1.1 million in cash and cash equivalents.

As of December 31, 2024, the Company had 7,727,243 common shares outstanding, as adjusted for the 1-for-25 reverse stock split of the Company’s common stock, effected on November 25, 2024.

During the quarter ended December 31, 2024, the Company received gross proceeds of $3 million from the issuance of equity. An additional $3.5 million in gross proceeds was received in January 2025 from the issuance of equity through the Company’s "at-the-market" facility and a registered direct offering of common stock and warrants. The Company expects to raise additional capital to support operations.

Research and Development (R&D) Expenses

R&D expenses were $2.1 million for the first quarter ended December 31, 2024, compared to $2.6 million for the first quarter ended December 31, 2023. The decrease in R&D expenses primarily reflects the completion of the Halo-Lido Phase 2 and Mino-Lok Phase 3 trials, offset by an increase in LYMPHIR-related expenses due to additional headcount and ongoing investigator-initiated trials.

We expect that research and development expenses will continue to decrease in fiscal 2025 because we have completed the Phase 3 trial for Mino-Lok and we remain focused on the commercialization of LYMPHIR through our majority-owned subsidiary, Citius Oncology, Inc.

General and Administrative (G&A) Expenses

G&A expenses were $5.4 million for the first quarter ended December 31, 2024, compared to $3.7 million for the first quarter ended December 31, 2023. The increase was primarily due to higher costs for pre-launch sales and marketing activities associated with LYMPHIR. General and administrative expenses consist primarily of compensation costs, professional fees for legal, regulatory, accounting, and corporate development services, and investor relations expenses.

Stock-based Compensation Expense

For the first quarter ended December 31, 2024, stock-based compensation expense was $2.5 million as compared to $3.1 million for the prior year. Stock-based compensation expense during the quarter ended December 31, 2024 is primarily related to the Citius Oncology Plan. The decrease compared to the prior year is due to lower costs associated with the Citius Pharma stock plans.

Net loss

Net loss was $10.3 million, or ($1.30) per share for the quarter ended December 31, 2024, compared to a net loss of $9.2 million, or ($1.45) per share for the quarter ended December 31, 2023, as adjusted for the reverse stock split. The increase in net loss was due to the increase in general and administrative expenses partially offset by lower research and development expense.

On February 14, 2025 Veracyte, Inc. (Nasdaq: VCYT), a leading cancer diagnostics company, reported that new data presented at the 2025 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) demonstrate the performance and clinical utility of its Decipher Prostate and Decipher Bladder tests to help guide treatment for patients with prostate and bladder cancer (Press release, Veracyte, FEB 14, 2025, View Source [SID1234650289]). Presented findings also show that the company’s Decipher GRID (Genomic Resource for Intelligent Discovery) research tool is enabling new data-based insights that in the future may help further advance personalized cancer care. The findings are from among 17 Decipher-focused abstracts being presented at the conference this week in San Francisco, as well as a new paper published in Annals of Oncology.

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"The breadth and depth of Decipher-focused data presented at the ASCO (Free ASCO Whitepaper) GU Symposium reinforce the widespread impact our Decipher tests are having on clinical care, as well as on research into the molecular underpinnings of prostate and bladder cancers," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "They also demonstrate Veracyte’s commitment to clinical rigor and evidence development. We are grateful for our ongoing collaborations with leading clinician-researchers, which are enabling us to continue driving innovation that can further help patients."

Key findings presented at the ASCO (Free ASCO Whitepaper) GU Symposium are:

Poster (Abstract #399): Decipher Score as a Predictor of Response to Treatment Intensification in the NRG Oncology-RTOG 0534 (SPPORT) Phase III Randomized Post-Prostatectomy Salvage Radiotherapy Trial. Presented by Alan Pollack, M.D., Ph.D., University of Miami Health System.

This study found that the Decipher Prostate Genomic Classifier may inform treatment-intensification strategies for patients undergoing salvage radiotherapy by identifying those who will benefit from pelvic nodal radiation. The findings are from a post-hoc analysis of the NRG Oncology/RTOG 0534 (SPPORT) Phase 3, randomized trial. Decipher Prostate test results were obtained for 709 patients who experienced biochemical recurrence following prostatectomy and were allocated to three treatment study arms: 1.) prostate bed radiation therapy alone (PBRT); 2.) PBRT and short-term androgen deprivation therapy (STADT); or 3.) PBRT, STADT and pelvic lymph node radiation therapy (PLNRT). They found that patients with high Decipher Prostate scores received greater benefit from the addition of PLNRT and STADT to PBRT, compared to those with low genomic test scores.

"The addition of pelvic node radiotherapy to PBRT and short-term ADT is becoming more frequently used for patients with high-risk prostate cancer undergoing salvage radiation," said Dr. Davicioni, an author on the study. "Accurately determining which patients are likely to benefit from this strategy, however, can be challenging but is especially important given its additional toxicity and potential side effects. Our findings show that Decipher Prostate test results can provide physicians with important information to help guide treatment decision-making with their patients."

Poster (Abstract #831): A non-coding RNA based classifier for favorable outcomes in clinically organ confined bladder cancer. Presented by Yair Lotan, M.D., UT Southwestern Medical Center.

In this study, researchers demonstrated that the Decipher Bladder Genomic Subtyping Classifier accurately identified patients whose bladder cancer was less aggressive, based on their cancer’s molecular subtype. The study involved 226 patients with high-grade, clinically organ-confined bladder cancer who subsequently underwent radical cystectomy without any neoadjuvant therapy. The researchers found that patients with the luminal favorable bladder cancer subtype, compared to those without it, had significantly lower likelihood of being upstaged to T3+ disease (OR 0.32, 95% CI 0.12-0.82; P= 0.02) or to any upstaging (OR 0.41, 95% CI 0.20-0.83; P=0.01). They also found that the luminal favorable subtype was significantly associated with better overall survival (HR 0.33, 95% CI 0.15-0.74; P=0.007).

"Accurate clinical staging in bladder cancer can be challenging, limiting clinicians’ ability to guide treatment decisions for their patients," said Dr. Lotan. "Our findings suggest that molecular subtyping information provided by the Decipher Bladder test can help physicians better identify which patients have less-aggressive bladder cancer and may not require treatment intensification."

Oral Presentation (Abstract #308): Gene signature predictor of dose-response to prostate radiation: validation of PORTOS in phase III trials. Presented by Shuang Zhao, M.D., University of Wisconsin-Madison.

This study’s oral presentation at the ASCO (Free ASCO Whitepaper) GU Symposium also corresponded with its publication in Annals of Oncology. The findings demonstrate that PORTOS (Post-Operative Radiation Therapy Outcomes Score), a genomic signature developed using Veracyte’s Decipher GRID research tool, predicts which patients with prostate cancer are likely to benefit from differing dosages of salvage and definitive radiation therapy. The findings are from post-hoc analyses of the SAKK 09/10 and NRG Oncology/RTOG 0126 Phase 3, randomized clinical trials.

Among the 226 patients evaluated from the SAKK 09/10 trial, those with higher PORTOS scores were significantly more likely to benefit from dose-increased (70 Gy vs. 64 Gy) salvage radiotherapy, compared to those with lower PORTOS scores. Additionally, among 215 patients undergoing definitive radiotherapy in the NRG Oncology/RTOG 0126 trial, those with higher PORTOS scores were more likely to benefit from dose escalation (79.2 Gy vs. 70.2 Gy), compared to those with lower PORTOS scores. An analysis using the whole-transcriptome-based Decipher GRID research tool’s database showed that there were no strong associations between the PORTOS signature and clinicopathologic variables such as race, PSA levels, clinical stage, grade group or NCCN risk status.

"Physicians are currently limited in their tools for determining which patients with prostate cancer will benefit from dose-escalated radiation therapy. Our findings, derived from two Phase 3, randomized trials, suggest that the research-based PORTOS signature has potential to be a useful clinical tool to help inform important radiation treatment decisions for patients following a prostate cancer diagnosis or who are experiencing biochemical recurrence," said Dr. Zhao, who also helped develop the PORTOS signature.

About Decipher Prostate

The Decipher Prostate Genomic Classifier is a 22-gene test, developed using RNA whole-transcriptome analysis and machine learning, that helps inform treatment decisions for patients with prostate cancer. The test is performed on biopsy or surgically resected samples and provides an accurate risk of developing metastasis with standard treatment. Armed with this information, physicians can better personalize their patients’ care and may recommend less-intensive options for those at lower risk or earlier, more-intensive treatment for those at higher risk of metastasis. The Decipher Prostate test has been validated in many dozens of published studies involving more than 100,000 patients. It is the only gene expression test to achieve "Level IB" evidence status and inclusion in the risk-stratification table in the most recent NCCN Guidelines* for prostate cancer. More information about the Decipher Prostate test can be found here.

About Decipher Bladder

The Decipher Bladder Genomic Subtyping Classifier is a 219-gene test, developed using RNA whole-transcriptome analysis and machine learning, that is designed for use in patients following bladder cancer diagnosis who face questions regarding treatment intensity. The test classifies bladder tumors into five molecular subtypes, each having distinct tumor biology and potential clinical implications. This information can help physicians and their patients better understand the degree of benefit that would likely be gained from neoadjuvant chemotherapy and/or the likelihood of harboring non-organ-confined disease at time of surgery, respectively. More information about the Decipher Bladder test can be found here.

About Decipher GRID

The Decipher GRID database includes more than 200,000 whole-transcriptome profiles from patients with urologic cancers and is used by Veracyte and its partners to contribute to continued research and help advance understanding of prostate and other urologic cancers. GRID-derived information is available on a Research Use Only basis. More information about Decipher GRID can be found here.

On February 14, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported results from the subgroup analyses of the pivotal ENVISION study evaluating the impact of tumor burden and focality on the response to UGN-102, an investigational drug in development for treatment of LG-IR-NMIBC (Press release, UroGen Pharma, FEB 14, 2025, View Source [SID1234650288]). Analyses of pre-specified subgroups showed comparable CR rates and DOR patterns across different levels of tumor burden (defined as the sum of the diameters of all visible tumors) and number of tumors at baseline in patients treated with UGN-102. The poster presentation titled, Impact of Tumor Burden or Focality in Recurrent Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer on Response to Treatment with UGN-102: A Substudy of the Phase 3 ENVISION Trial was presented today at ASCO (Free ASCO Whitepaper) GU 2025.

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"In this subgroup analysis on tumor burden and focality from the ENVISION study, the overall CR rate was consistent, and a majority of patients maintained their response 12 months after achieving CR at three months," said Sandip M. Prasad, M.D., Director of Urology at Morristown Medical Center and lead author of the study. "These results provide evidence of UGN-102’s potential to become an effective and durable treatment option for patients with recurrent LG-IR-NMIBC, regardless of tumor size or focality."

The ENVISION study included 240 patients with recurrent LG-IR-NMIBC who received at least one dose of UGN-102 and 95% (228 patients) received all six weekly intravesical instillations of UGN-102. In this pre-specified analysis CR rates were 82.8% for patients with a tumor burden ≤3 cm (n=149/180) compared to 73.2% for those with a tumor burden >3 cm (n=30/41). Of the patients with CR at three months, 15.4% vs 20.0% experienced recurrence of low-grade disease, progression (either in stage or grade), or death (unrelated to treatment) by 15 months. In the 191 patients with multiple vs single tumors who achieved a CR, the three-month CR was 79.3% vs 82.9%, with recurrence rates of 18.5% vs 11.8%.

"We are encouraged by these results, which highlight the potential of UGN-102 to provide durable responses in patients with recurrent LG-IR-NMIBC," said Mark Schoenberg, M.D., Chief Medical Officer of UroGen. "These pre-specified subgroup analyses further strengthen the growing body of evidence supporting UGN-102 as a treatment option for patients dealing with the challenges of disease recurrence and the need for repeated surgeries."

The ENVISION trial’s primary efficacy and safety results, previously presented, showed that UGN-102 delivered a 79.6% CR rate at three months, with an unprecedented 82.3% probability of remaining in response 12 months later by Kaplan-Meier estimates.

These findings further support UGN-102’s potential to alter the treatment landscape for patients with LG-IR-NMIBC, a condition where recurrence and progression remain significant clinical challenges.

UroGen initiated the submission of a rolling new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment for LG-IR-NMIBC in January 2024 and completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 with a Prescription Drug User Fee Act (PDUFA) goal date of June 13, 2025.

The most common treatment-emergent adverse events (TEAEs) in the ENVISION trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. The TEAEs were typically mild-to-moderate in severity and either resolved or were resolving. The ENVISION trial demonstrated a similar safety profile to that observed in other studies of UGN-102.

Study limitations include the small sample size of the comparator groups and the single arm design.

The analysis in another presentation titled, Treatment of Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer with UGN-102: Results of the Phase 3 ATLAS and ENVISION Studies highlights that in both studies, the CR rate in patients initially treated with UGN-102 was robust, with the majority of patients remaining event-free at 12 months after a three-month CR. A new analysis from the ATLAS trial highlights 54% decreased risk of recurrence, progression or death with UGN-102 compared to TURBT. The hazard ratio for DOR in ATLAS was 0.46 with a 95% confidence interval (0.24, 0.86) favoring the UGN-102 arm. Median DOR was not estimable in any arm due to low recurrence rates; the most common adverse event with UGN-102 in both studies was dysuria, occurring in 22.5% in ENVISION and 30.4% in ATLAS.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting by a trained healthcare professional. UroGen completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 and assigned a PDUFA goal date of June 13, 2025.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

In the U.S., bladder cancer is the second most common urologic cancer in men. LG-IR-NMIBC represents approximately 23,000 newly diagnosed bladder cancer patients each year and an estimated 59,000 recurrences annually among patients diagnosed in previous years. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. Guideline recommendations for the management of NMIBC include trans-urethral resection of bladder tumor (TURBT) as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures.

About ENVISION

The Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as a chemoablative therapy in patients with LG-IR-NMIBC. The Phase 3 ENVISION trial completed target enrollment with approximately 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the CR rate at the three-month assessment after the first instillation, and the key secondary endpoint evaluated durability over time in patients who achieved a CR at the three-month assessment. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550).