On April 26, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported an updated 18-month DOR of 80.6% (95% CI: 74.0, 85.7), by Kaplan-Meier estimate, from the Phase 3 ENVISION trial of UGN-102 (mitomycin) for intravesical solution, an investigational treatment for recurrent LG-IR-NMIBC (Press release, UroGen Pharma, APR 26, 2025, View Source [SID1234652195]). These data were featured today in an Oral Presentation Session (Abstract ID: PD12) at the AUA 2025 Annual Meeting in Las Vegas, Nevada.

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"This new update from the pivotal ENVISION trial of UGN-102 demonstrated a compelling probability of remaining in complete response of 80.6% at 18 months in patients who achieved a complete response (CR) at three months (79.6%)," said Sandip Prasad M.D., M.Phil., Director of Genitourinary Surgical Oncology, Vice Chair of Urology at Morristown Medical Center/Atlantic Health System, NJ, and Principal Investigator of the ENVISION trial. "Low-grade bladder cancer is a persistent cancer that frequently recurs and comes with its own risks. There is a significant unmet need in finding treatment options for patients with recurrent low-grade bladder cancer."

The existing standard of care for LG-IR-NMIBC is an invasive surgical procedure requiring anesthesia called transurethral resection of bladder tumor (TURBT). Repeated TURBT procedures can impact patients’ physical health and quality of life and are even associated with an increased risk in mortality. Due to high recurrence rates, LG-IR-NMIBC patients, who are typically elderly with comorbidities, will likely need multiple TURBTs under general anesthesia over the course of their lifetime. An estimated 59,000 patients with LG-IR-NMIBC recur annually and face the burden and risks of repeat surgeries that often provide limited value.

Mark Schoenberg, M.D., Chief Medical Officer of UroGen, stated, "The duration of response data from the ENVISION trial further underscores UGN-102’s potential to positively impact the treatment landscape for patients with recurrent LG-IR-NMIBC. Many of these patients are elderly and face the burden of repeated surgeries under general anesthesia, highlighting the urgent need for innovative treatment options. If approved, we believe UGN-102’s potential to deliver durable complete responses, reduce recurrence rates, and extend treatment-free intervals would represent a significant advancement in the management of recurrent LG-IR-NMIBC."

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. Median follow-up time at 18 months was 18.7 months after the three-month CR.

UroGen completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment for LG-IR-NMIBC ahead of schedule, and the FDA accepted the NDA for UGN-102 with a Prescription Drug User Free Act (PDUFA) goal date of June 13, 2025.

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 recurrent 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 submission of the rolling NDA for UGN-102 in August 2024, 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)

LG-IR-NMIBC affects around 82,000 people in the U.S. every year and of those, an estimated 59,000 are recurrent. 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 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 pivotal 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 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).

On April 26, 2025 Pfizer Inc. (NYSE: PFE) reported results from the pivotal Phase 3 CREST trial of sasanlimab, an investigational anti-PD-1 monoclonal antibody (mAb), in combination with standard of care (SOC) Bacillus Calmette-Guérin (BCG) as induction therapy with or without maintenance in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC) (Press release, Pfizer, APR 26, 2025, View Source [SID1234652209]). The trial met its primary endpoint of event-free survival (EFS) by investigator assessment, demonstrating a clinically meaningful and statistically significant improvement with sasanlimab in combination with BCG (induction and maintenance) as compared to BCG alone (induction and maintenance): Hazard Ratio (HR) of 0.68; 95% Confidence Interval (CI), 0.49-0.94; 2-sided p=0.019; median EFS not yet reached. These findings show a 32% reduction in risk of disease-related events, including high-grade disease recurrence or progression, with the sasanlimab combination regimen as compared with SOC treatment alone. Pre-specified subgroup analyses for patients harboring higher risk disease showed consistent benefit with EFS HR of 0.63 (0.41, 0.96) for T1 disease, and EFS HR 0.53 (0.29, 0.98) for those with CIS disease.

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EFS was a composite endpoint defined as the time from randomization to the earliest of recurrence of high-grade disease, progression of disease, persistence of carcinoma in situ (CIS), or death due to any cause. The probability of being event-free at 36 months was 82.1% (95% CI, 77.4-85.9) with sasanlimab in combination with BCG (induction and maintenance), and 74.8% (95% CI, 69.7-79.2) with BCG alone (induction and maintenance). Results from the CREST trial are being presented today in a plenary oral presentation at the 2025 American Urological Association (AUA) Annual Meeting.

"New bladder cancer treatment options that help reduce rates of disease recurrence or progression are long overdue. Up to 50% of patients with high-risk non-muscle invasive bladder cancer may experience failure of BCG intravesical immunotherapy, yet it has been the standard of care after tumor resection for decades," said Neal Shore, M.D., FACS, Medical Director for START Carolina Research Center, and lead investigator for the CREST trial. "These Phase 3 results show that combining sasanlimab with BCG induction and maintenance therapy earlier in the course of the disease significantly prolonged event-free survival, highlighting the value and potential of sasanlimab in combination with BCG to redefine the treatment paradigm and reduce the burden for patients."

As the ninth most common cancer worldwide, bladder cancer accounts for up to 220,000 deaths annually.1,2 NMIBC, in particular, represents approximately 75% of all bladder cancer cases.3 In the U.S., it is estimated that about 38,000 people have high-risk NMIBC.4 While BCG treatment has been shown to reduce the risk of tumor recurrence, approximately 40-50% of patients with high-risk NMIBC receiving BCG will eventually have disease recurrence or progression despite therapy.5-7

"Today’s pivotal Phase 3 CREST results offer a much-needed therapeutic breakthrough and spotlight sasanlimab as the first immunotherapy combination with BCG to significantly improve outcomes for patients with BCG-naïve, high-risk NMIBC in over three decades," said Megan O’Meara, M.D., Interim Chief Development Officer, Pfizer Oncology. "The CREST findings are especially impactful for these patients with early-stage cancer who may benefit the most from innovative treatment regimens, including a subcutaneous immune checkpoint inhibitor, that delay disease recurrence or progression. These results underscore our long-standing commitment to patients with bladder cancer across all stages of the disease. We look forward to working with global regulatory authorities to potentially bring sasanlimab as an important new treatment option to patients with high-risk NMIBC."

Sasanlimab in combination with BCG (induction only) did not result in prolongation of EFS when compared to BCG alone (induction and maintenance), a key secondary endpoint: HR of 1.16; 95% CI, 0.87-1.55; 2-sided p=0.312, underscoring the need for BCG maintenance not only as a component of SOC treatment but also in combination with sasanlimab. Early interim analysis for the key secondary overall survival (OS) endpoint suggested no difference between treatment arms, with a median follow-up of 40.9 months. The study continues for survival follow-up until the final analysis. Complete response (CR) and duration of CR were additional secondary endpoints for patients with CIS at randomization. The CR rate achieved at any time was 89.8% with sasanlimab in combination with BCG (induction and maintenance) and 85.2% with BCG alone (induction and maintenance). Notably, for those patients with CIS at randomization who achieved a CR, the probability of remaining in CR at 36 months was 91.7% with sasanlimab in combination with BCG (induction and maintenance) compared to 67.7% with BCG alone (induction and maintenance).

The overall safety profile of sasanlimab in combination with BCG was generally consistent with the known profile of BCG and data reported from clinical trials with sasanlimab. The profile of sasanlimab was also generally consistent with the reported safety profile of PD-1 inhibitors. Pfizer has shared these data with global health authorities to support potential regulatory filings.

About CREST

The CREST trial is a Phase 3, multinational, randomized, open-label, three parallel-arm study of sasanlimab, an anti-PD-1 mAb, in combination with BCG (BCG induction with or without BCG maintenance) versus BCG (induction and maintenance) in participants with BCG-naïve, high-risk NMIBC. Patients were randomized to receive sasanlimab 300 mg by subcutaneous (SC) injection every four weeks up to cycle 25 (cycle = four weeks), in combination with BCG once weekly for six consecutive weeks (induction period) followed (Arm A; n=352) or not (Arm B; n=352) by maintenance with BCG, or BCG induction and maintenance up to cycle 25 (Arm C; n=351). The primary endpoint is EFS as assessed by the investigator, between Arm A and C, defined as a composite endpoint that combines time from randomization to the earliest of recurrence of high-grade disease, progression of disease, persistence of CIS, or death. Key secondary endpoints include EFS as assessed by the investigator between Arm B and Arm C, between Arms A/B and Arm C. In patients with CIS, CR and duration of CR were secondary endpoints. For more information on the CREST trial (NCT04165317), go to www.clinicaltrials.gov.

About Sasanlimab

Sasanlimab is a humanized immunoglobulin G4 (IgG4) mAb that binds to human PD-1 to block its interaction with PD-1 and PD-L1/PD-L2. PD-1 is a protein expressed on T cells, dendritic cells, natural killer cells, macrophages, and B cells, that functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands and may play an important role in tumor evasion from host immunity. It can be administered through a once every four weeks SC injection by prefilled syringe (2mL).

In early-stage clinical studies, sasanlimab administered at 300 mg SC every four weeks showed clinical efficacy in advanced solid tumors and advanced urothelial cancer. In addition to NMIBC, sasanlimab is being evaluated in several ongoing clinical trials in combination with Pfizer’s antibody drug conjugate (ADC) portfolio.

On April 26, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported updated results from its ongoing Phase 2 open-label ADVANCED-2 trial assessing intravesical TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with carcinoma in situ, or CIS (± Ta/T1), who are Bacillus Calmette-Guérin (BCG)-Unresponsive or BCG-Naïve (Press release, Protara Therapeutics, APR 26, 2025, View Source [SID1234652191]). The results will be featured today during an interactive poster session at the American Urological Association 2025 Annual Meeting in Las Vegas.

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"For patients with high-risk NMIBC, there are few effective and durable therapies available other than radical cystectomy, which we know is quite difficult for patients to tolerate," said Tom Jayram, M.D., Director of the Advanced Therapeutics Center at Urology Associates, and ADVANCED-2 study investigator. "TARA-002 has shown impressive efficacy, safety profile, and 12-month durability in its Phase 2 trial. In the clinic, we have seen TARA-002 become easily integrated into workflow without major hurdles for the patients or staff. This combination of clinical activity and ease of use makes me optimistic about TARA-002 having a meaningful impact in clinical practice."

Interim Results

BCG-Unresponsive Cohort

The BCG-Unresponsive dataset includes a total of five patients, all of whom were six- and nine-month evaluable, and three of whom were evaluable at 12 months as of an April 16, 2025 data cutoff.

The complete response (CR) rate at any time in BCG-Unresponsive patients was 100% (5/5).
The CR rate in BCG-Unresponsive patients was 100% (5/5) at six months, 80% (4/5) at nine months, and 67% (2/3) at 12 months.
BCG-Naïve Cohort

The BCG-Naïve dataset includes a total of 21 patients, including 16 evaluable at six months, eight at nine months, and seven at 12 months as of an April 16, 2025 data cutoff.

The CR rate at any time in BCG-Naïve patients was 76% (16/21).
The CR rate in BCG-Naïve patients was 63% (10/16) at six months, 63% (5/8) at nine months, and 43% (3/7) at 12 months.
Safety

The majority of adverse events were Grade 1 and transient with no Grade 3 or greater treatment-related adverse events (TRAEs) as assessed by study investigators. No patients discontinued treatment due to TRAEs. The most common adverse events were in line with typical responses to bacterial immunopotentiation, such as flu-like symptoms. The most common urinary symptoms reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation, and urinary tract infection. Most bladder irritations resolved shortly after administration or within a few hours to a few days.

"The durable results shared today continue to support our conviction that TARA-002 has the potential to make a meaningful difference in the lives of patients with NMIBC," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "Notably, we are particularly pleased with the competitive 12-month CR rates observed in the registrational BCG-Unresponsive cohort as well as the BCG-Naïve cohort. We look forward to continuing to advance this important trial as we work toward our mission of bringing transformative therapies to patients."

The Company continues to expect to present an interim update with results from approximately 25 six-month evaluable BCG-Unresponsive patients by the end of 2025.

Conference Call and Webcast

Protara will host a conference call and webcast to discuss the data on Monday, April 28, 2025, at 8:30 am ET. The live call can be accessed by registering as a participant here. Upon registration, participants will receive conference call dial-in information. A live webcast of the event can be accessed by visiting the Events and Presentations section of the Company’s website: View Source The webcast will be archived for a limited time following the presentation.

About ADVANCED-2

ADVANCED-2 (NCT05951179) is a Phase 2 open-label trial assessing intravesical TARA-002 in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive (n≈100) and BCG-Naïve (n=31). The BCG-Unresponsive cohort has been designed to be registrational in alignment with the U.S. Food and Drug Administration’s 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment, Draft Guidance for Industry.

About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma IL-6, IL-10, IL-12. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

On April 25, 2025 Daiichi Sankyo reported Consolidated Financial Results for Year Ended March 31, 2025 (Fiscal 2024) (Filing, 3 mnth, MAR 31, Daiichi Sankyo, 2025, APR 25, 2025, View Source [SID1234654298]).

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On April 25, 2025 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported new preclinical proof-of-concept data for its novel HER3 antibody-drug conjugate (ADC), EO-1022 (Press release, Elevation Oncology, APR 25, 2025, View Source;utm_medium=rss&utm_campaign=elevation-oncology-presents-preclinical-proof-of-concept-data-for-eo-1022-at-the-american-association-for-cancer-research-aacr-annual-meeting-2025 [SID1234652142]). The data will be presented in a late-breaking poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, being held April 25-30 in Chicago, Illinois.

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"We designed EO-1022 with several notable features, including glycan site-specific conjugation and MMAE payloads, in order to address the significant need for a novel HER3 ADC that can potentially deliver improved efficacy and safety to patients with a range of solid tumors," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "Today, we are excited to share preclinical proof-of-concept data for EO-1022, which indicate enhanced stability and anti-tumor activity than benchmark HER3 ADCs in the models tested in vitro and in vivo. We believe these findings support the potential of EO-1022 in treating multiple HER3-expressing cancers and look forward to progressing this program toward the clinic."

EO-1022 is an ADC containing seribantumab, a fully human IgG2 anti-HER3 monoclonal antibody, which is site-specifically conjugated at glycan to the monomethyl auristatin E (MMAE) payload with a drug-to-antibody ratio (DAR) of 4. Elevation Oncology designed EO-1022 leveraging the site-specific ADC technology platform licensed from Synaffix B.V. Elevation Oncology is developing EO-1022 for the treatment of solid tumors that express HER3, including breast cancer and non-small cell lung cancer. Elevation Oncology expects to file an Investigational New Drug (IND) application for EO-1022 in 2026.

In a poster titled, "Preclinical discovery and characterization of EO-1022, a site-specific glycan-conjugated anti-HER3 vc-MMAE ADC for treating solid tumors," Elevation Oncology scientists will present in vitro and in vivo data that show:

EO-1022 is highly stable in human serum, with a homogenous DAR of 4 and minimal free payload compared to seribantumab-vcMMAE and patritumab-DXd, two benchmark HER3 ADCs, both of which use stochastic conjugation. These findings illustrate that a key feature of EO-1022 is minimal systemic exposure to free payload, potentially resulting in reduced payload-associated toxicity in patients and an improved safety profile.
EO-1022 exhibits potent in vitro cytotoxicity that is dependent on HER3 expression levels.
EO-1022 elicits anti-tumor activity in in vivo models of low, medium and high HER3 expression levels, including in a patient derived xenograft (PDX) model of low HER3-expressing EGFR-mutant lung cancer.
The poster presentation is now available in the "Publications" section of Elevation Oncology’s website: View Source

About EO-1022

Elevation Oncology is developing EO-1022, a potentially differentiated HER3 ADC for the treatment of HER3-expressing solid tumors, including breast cancer and non-small cell lung cancer. EO-1022 consists of seribantumab, a fully human IgG2 anti-HER3 antibody, site-specifically conjugated at glycan to the MMAE payload with a DAR of 4. It leverages seribantumab’s desirable internalization properties and advanced site-specific ADC technology which makes possible the use of the potent cytotoxic MMAE payload. Elevation Oncology expects to file an IND application in 2026.