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 encouraging safety data from the Phase 1 dose-escalation study for UGN-301 (zalifrelimab) intravesical solution, an investigational drug in development for the treatment of recurrent non-muscle invasive bladder cancer (NMIBC) (Press release, UroGen Pharma, APR 26, 2025, View Source [SID1234652194]).

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"The early safety profile and clinical activity results from this study are encouraging," said Jay Raman, M.D., Professor and Chair of Urology, and Professor of Surgery, Penn State Cancer Institute, PA. "This innovative approach of localized drug delivery combined with immune modulation merits additional investigation in the treatment of non-muscle invasive bladder cancer."

The multi-part clinical study included up to 30 patients per arm, aimed to assess safety and determine the recommended Phase 2 dose of UGN-301 as monotherapy and in combination with other agents. In the monotherapy arm, dose escalation continued to the maximum feasible dose. No dose-limiting toxicities and no treatment-emergent adverse events leading to treatment discontinuation were observed. This study also demonstrated that local delivery of UGN-301 formulated in our proprietary reverse thermal gel (RTGel) allowed sustained exposure of zalifrelimab in the bladder with limited systemic exposure, which mitigated the risk of systemic immune-related toxicities associated with CTLA-4 inhibition.

With respect to clinical activity observed in the trial, among evaluable patients who received UGN-301, 46% (6 of 13) of those with Ta/T1 disease and 33% (2 of 6) of those with carcinoma in situ (CIS) ± Ta/T1 disease were recurrence-free or had achieved a complete response at week 12. Notably, 60% (3 of 5) of patients with Ta/T1 disease treated with 300 mg continued to remain recurrence-free at the 15-month disease assessment, including one patient with high-grade T1 disease. In the 500 mg cohort, 25% (1 of 4) of patients with CIS disease and 33% (1 of 3) of patients with Ta/T1 disease remained disease-free at six months, both of whom are still active participants in the study.

These findings highlight the potential of UGN-301 as a targeted treatment for NMIBC with an acceptable safety profile. Presentation of data from the combination arms is planned for later this year.

"Our hypothesis is that UGN-301’s unique formulation could potentially offer the dual benefits of maximizing therapeutic activity while minimizing systemic side effects, a key challenge in cancer immunotherapy," said Mark Schoenberg, Chief Medical Officer, UroGen. "Although this requires additional clinical investigation, we are encouraged by the potential of UGN-301 as an investigational treatment for patients with recurrent NMIBC."

About Non-Muscle Invasive Bladder Cancer and High-Grade Disease

In the U.S., bladder cancer is the second most common urologic cancer in men. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a serious and potentially life-threatening form of bladder cancer that remains confined to the inner layers of the bladder wall but exhibits aggressive behavior and a higher risk of progression. In the U.S., HG-NMIBC accounts for approximately 30–40% of all newly diagnosed NMIBC cases. Patients with HG-NMIBC face a significantly elevated risk of recurrence and progression to muscle-invasive disease, necessitating close surveillance and aggressive treatment. The standard of care includes complete transurethral resection of bladder tumor, often followed by intravesical therapy such as Bacillus Calmette-Guérin (BCG). However, BCG has a treatment failure rate of approximately 40-50%, leaving patients with limited treatment options short of radical cystectomy. Given the high recurrence and progression rates, HG-NMIBC presents a substantial clinical and quality-of-life burden. Upon recurrence, which occurs in approximately 70% of patients, the patients undergo another round of BCG therapy with a response rate of approximately 30%.

About UGN-301

UGN-301 is an anti-CTLA-4 monoclonal antibody (zalifrelimab), originally licensed from Agenus Inc. in 2019. It is formulated with RTGel, our proprietary reverse-thermal hydrogel, for intravesical administration into the bladder. Intravesical administration of UGN-301 is designed to increase drug concentrations in the bladder without significant systemic exposure, potentially diminishing the systemic toxicity associated with CTLA-4 blockade. UroGen is evaluating UGN-301 in a multi-arm Phase 1 study of UGN-301 as monotherapy and in combination with other agents. The safety of UGN-301 is being evaluated in the monotherapy arm of the study as combination therapy for HG-NMIBC.

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 25, 2025 AbbVie (NYSE:ABBV) reported financial results for the first quarter ended March 31, 2025 (Press release, AbbVie, APR 25, 2025, View Source [SID1234652133]).

"AbbVie’s first-quarter results were well ahead of our expectations and reflect an excellent start to the year," said Robert A. Michael, chief executive officer, AbbVie. "The fundamentals of our business are strong and we continue to bolster our outlook with pipeline advancements and strategic investments. Based on the progress we are making, AbbVie is well positioned for the long term."

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First-Quarter Results

•Worldwide net revenues were $13.343 billion, an increase of 8.4 percent on a reported basis, or 9.8 percent on an operational basis.

•Global net revenues from the immunology portfolio were $6.264 billion, an increase of 16.6 percent on a reported basis, or 18.1 percent on an operational basis.
◦Global Skyrizi net revenues were $3.425 billion, an increase of 70.5 percent on a reported basis, or 72.0 percent on an operational basis.
◦Global Rinvoq net revenues were $1.718 billion, an increase of 57.2 percent on a reported basis, or 59.7 percent on an operational basis.
◦Global Humira net revenues were $1.121 billion, a decrease of 50.6 percent on a reported basis, or 49.5 percent on an operational basis.

•Global net revenues from the neuroscience portfolio were $2.282 billion, an increase of 16.1 percent on a reported basis, or 17.0 percent on an operational basis.
◦Global Vraylar net revenues were $765 million, an increase of 10.3 percent.
◦Global Botox Therapeutic net revenues were $866 million, an increase of 15.8 percent on a reported basis, or 17.0 percent on an operational basis.
◦Global Ubrelvy net revenues were $240 million, an increase of 17.8 percent on a reported basis, or 18.0 percent on an operational basis.
◦Global Qulipta net revenues were $193 million, an increase of 47.6 percent on a reported basis, or 48.3 percent on an operational basis.

•Global net revenues from the oncology portfolio were $1.633 billion, an increase of 5.8 percent on a reported basis, or 7.5 percent on an operational basis.
◦Global Imbruvica net revenues were $738 million, a decrease of 11.9 percent.
◦Global Venclexta net revenues were $665 million, an increase of 8.3 percent on a reported basis, or 12.3 percent on an operational basis.
◦Global Elahere net revenues were $179 million.

•Global net revenues from the aesthetics portfolio were $1.102 billion, a decrease of 11.7 percent on a reported basis, or 10.2 percent on an operational basis.
◦Global Botox Cosmetic net revenues were $556 million, a decrease of 12.3 percent on a reported basis, or 10.7 percent on an operational basis.
◦Global Juvederm net revenues were $231 million, a decrease of 22.2 percent on a reported basis, or 20.0 percent on an operational basis.

•On a GAAP basis, gross margin in the first quarter was 70.0 percent. The adjusted gross margin was 84.1 percent.

•On a GAAP basis, selling, general and administrative (SG&A) expense was 24.7 percent of net revenues. The adjusted SG&A expense was 24.6 percent of net revenues.

•On a GAAP basis, research and development (R&D) expense was 15.5 percent of net revenues. The adjusted R&D expense was 15.4 percent of net revenues.

•Acquired IPR&D and milestones expense was 1.9 percent of net revenues.

•On a GAAP basis, operating margin in the first quarter was 28.0 percent. The adjusted operating margin was 42.3 percent.

•Net interest expense was $627 million.

•On a GAAP basis, the tax rate in the quarter was 22.4 percent. The adjusted tax rate was 14.2 percent.

•Diluted EPS in the first quarter was $0.72 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $2.46. These results include an unfavorable impact of $0.13 per share related to acquired IPR&D and milestones expense.

Recent Events

•AbbVie announced that its board of directors unanimously elected chief executive officer (CEO) Robert A. Michael to assume the additional position of chairman of the board of directors, effective July 1, 2025. He will succeed Richard A. Gonzalez, who formerly served as AbbVie’s CEO and has been chairman since the Company’s formation in 2013.

•AbbVie announced that the European Commission (EC) granted marketing authorization to Rinvoq (upadacitinib) for the treatment of giant cell arteritis (GCA) in adult patients. The approval was supported by data from the pivotal Phase 3 SELECT-GCA trial which demonstrated that Rinvoq achieved the primary endpoint of sustained remission and key secondary endpoints, including reduction in disease flares, lower cumulative steroid exposure and complete remission. This authorization marks the eighth approved indication for Rinvoq in the European Union (EU).

•At the Society of Gynecologic Oncology (SGO) Annual Meeting, AbbVie announced final data analysis from the Phase 3 MIRASOL trial evaluating the efficacy and safety of Elahere (mirvetuximab soravtansine-gynx) in women with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer (PROC) compared to chemotherapy. At 30.5 months median follow-up, treatment with Elahere continued to show significant improvements in progression-free survival (PFS) and overall survival (OS) compared to investigator’s choice (IC) chemotherapy.

•AbbVie and Xilio Therapeutics, a clinical-stage biotechnology company, announced a collaboration and option-to-license agreement that will combine AbbVie’s oncology expertise with Xilio’s proprietary tumor-activation technology to develop novel immunotherapies, including masked T-cell engagers, for people living with cancer.

•AbbVie announced that it submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for approval of trenibotulinumtoxinE (BoNT/E) for the treatment of moderate to severe glabellar lines. TrenibotulinumtoxinE is a first-in-class botulinum neurotoxin serotype E characterized by a rapid onset of action as early as 8 hours after administration and short duration of effect of 2-3 weeks. If approved, trenibotulinumtoxinE will be the first neurotoxin of its kind available to patients.

•Allergan Aesthetics announced that the Allergan Medical Institute (AMI) will open three new state-of-the-art training centers in the U.S., expanding access to high-quality, tailored training for licensed aesthetics providers. The first training center is scheduled to open in Irvine, CA, with additional locations to follow in Atlanta, GA and Austin, TX.

•AbbVie and Gubra announced a license agreement to develop GUB014295 (ABBV-295), a potential best-in-class, long-acting amylin analog for the treatment of obesity. This partnership marks AbbVie’s entrance into the obesity field and under the terms of the agreement, AbbVie will lead development and commercialization of GUB014295 globally. Prior to the close of the agreement, Gubra announced positive interim results from Part A of a Phase 1 multiple ascending dose (MAD) study, which showed that GUB014295 was well tolerated with body weight loss that was sustained in a manner consistent with data from a previously announced single ascending dose (SAD) study.

•AbbVie announced that the FDA approved Emblaveo (aztreonam and avibactam), as the first monobactam/β-lactamase inhibitor combination antibiotic therapy to treat complicated intra-abdominal infections, including those caused by Gram-negative bacteria. The approval of Emblaveo was supported by prior findings regarding the efficacy and safety of aztreonam for the treatment of complicated intra-abdominal infections as well as clinical trial results from the Phase 3 REVISIT study, which evaluated the efficacy, safety, and tolerability of Emblaveo for the treatment of serious infections due to Gram-negative bacteria.

Full-Year 2025 Outlook

AbbVie is raising its adjusted diluted EPS guidance for the full year 2025 from $11.99 – $12.19 to $12.09 – $12.29, which includes an unfavorable impact of $0.13 per share related to acquired IPR&D and milestones expense incurred year-to-date through the first quarter 2025. The company’s 2025 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred beyond the first quarter of 2025, as both cannot be reliably forecasted. This guidance does not reflect the acquired IPR&D and milestones impact related to AbbVie and Gubra’s licensing agreement to develop GUB014295, as that transaction closed after the first quarter of 2025. Additionally, this guidance is based on the existing trade environment and does not reflect any trade policy shifts, including pharmaceutical sector tariffs, that could impact AbbVie’s business.

On April 25, 2025 Veracyte, Inc. (Nasdaq: VCYT), a leading genomic diagnostics company, reported the launch of its Decipher Prostate Metastatic Genomic Classifier for use in patients whose prostate cancer has spread beyond the primary tumor (Press release, Veracyte, APR 25, 2025, View Source [SID1234652150]). The Decipher Prostate test, already widely used for patients with localized disease, is now the only gene expression test available and covered by Medicare to inform treatment decisions for patients across the full continuum of prostate cancer risk.

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Veracyte has begun making the Decipher Prostate Metastatic test available to select clinical sites through an early access program and will begin taking orders for the test more broadly in June 2025.

Prostate cancer is the second-leading cause of cancer deaths among men in the United States and the rate of men diagnosed with advanced disease has been growing in recent years.1 Veracyte estimates that approximately 10% (or about 30,000) of all prostate cancers diagnosed annually in the United States are metastatic.2

"A number of treatment options are now available to increase survival for patients whose prostate cancer has metastasized," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "Until now, however, clinicians had limited ways to determine which of these patients will likely benefit from these therapies and which will not and may thus avoid their toxic side effects. We believe the Decipher Prostate Metastatic test will provide an important new tool to help clinicians make more-informed treatment recommendations for their patients with metastatic prostate cancer."

The Decipher Prostate test’s clinical validity and clinical utility for use in patients with metastatic prostate cancer have been demonstrated in multiple, prospective, Phase 3 clinical studies.3-6 These studies have shown that such patients with high Decipher scores are likely to have more-aggressive tumor biology compared to those with lower scores, informing the absolute benefit from treatment intensification. These findings build upon extensive data already established for the Decipher Prostate test’s use in patients with localized prostate cancer, where it is the only gene expression test to achieve "Level I" evidence status in the most recent NCCN Guidelines* for prostate cancer.

"Our expansion into metastatic prostate cancer underscores the power of the Veracyte Diagnostics Platform to uncover novel insights that can enable us to further help patients," said Philip Febbo, M.D., Veracyte’s chief scientific officer and chief medical officer.

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 across the full spectrum of prostate cancer. The test is performed on biopsy or surgically resected samples and conveys the aggressiveness of the cancer. For patients with localized or regional prostate cancer, the Decipher score indicates a patient’s risk of metastasis, helping to determine treatment timing and intensity. For patients with metastatic prostate cancer, the Decipher score indicates the likelihood of cancer progression and survival benefit with treatment intensification. Armed with this information, physicians can better personalize their patients’ care. The Decipher Prostate test’s performance and clinical utility has been demonstrated in over 85 studies involving more than 200,000 patients. It is the only gene expression test to achieve "Level I" evidence status and inclusion in the risk-stratification table in the most recent NCCN Guidelines* for prostate cancer.

On April 25, 2025 Researchers with City of Hope, one of the largest and most advanced cancer research and treatment organizations in the U.S. with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report, reported that it will present more than 74 chaired, plenary, educational, minisymposium, poster and other sessions on innovative clinical trial results, breakthrough diagnostic techniques and advances in treatment options at the AACR (Free AACR Whitepaper) Annual Meeting, which started April 25 and ends April 30 in Chicago (Press release, City of Hope, APR 25, 2025, View Source [SID1234652167]).

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In addition to City of Hope’s innovative research being presented throughout the meeting, David W. Craig, Ph.D., professor and founding chair of the Department of Integrative Translational Sciences within Beckman Research Institute of City of Hope, is chairing the final plenary session of the conference, "Opportunities in Predictive Oncology," on Wednesday from 8 to 10 a.m. CT. He will also present an educational session on using a biological analysis approach called multiomics to investigate the unique genetic makeup of different cell populations in solid tumors on Friday from 4:46 to 5:06 p.m. CT.

On Saturday from 10:00 to 11:30 a.m. CT, Michael A. Caligiuri, M.D., former president of City of Hope National Medical Center and professor in the Department of Hematology & Hematopoietic Cell Transplantation, will chair a session on advances in the application of natural killer (NK) cells and present on "Innate immune lymphocytes, including NK cells." He will also chair "Academic Entrepreneurship: Getting Your Discovery to Patients, Part 1—Liftoff" on Saturday from 8:00 to 9:30 a.m. CT, which will help define the steps required for translating research from the bench to the bedside.

As part of a session on advances in diagnostics and therapeutics, Hope Rugo, M.D., who recently joined City of Hope as director of its Women’s Cancers Program, will talk about new findings in managing toxicities from antibody-drug conjugates on Monday from 1:25 to 1:45 p.m. CT. Dr. Rugo will also serve as a discussant at the Clinical Trials Plenary Session on Biologics and T-cell Engagers on Tuesday from 10:15 a.m. to 12:15 p.m. CT.

Highlights of City of Hope research presented at the AACR (Free AACR Whitepaper) conference include:

Phase 3 clinical trial shows promising results for novel immunotherapy

Cancer of the nasopharynx, or the upper part of the throat that plays a crucial role in breathing and swallowing, is relatively rare. However, in certain regions like China and North Africa, the disease is much more common. To combat recurrent or metastatic nasopharyngeal carcinoma, a new immunotherapy drug has been tested in combination with standard chemotherapy.

Data from a phase 3 clinical trial of the medication called penpulimab resulted in the Food and Drug Administration (FDA) approving its use this past week in combination with cisplatin or carboplatin and gemcitabine for the first-line treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma. The FDA also approved penpulimab as a single agent for similar patients with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.

Medical oncologist Aditya Shreenivas, M.D., M.S. will present the supporting data from "Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304)" during a clinical trials minisymposium session on Sunday from 3:50 to 4:00 p.m. CT.

Penpulimab is an anti-PD-1 inhibitor, a type of treatment that helps the immune system recognize and attack cancer. Building on previous studies that have shown that the combination of PD-1 inhibitors with chemotherapy exhibits promising efficacy as a first-line treatment for Asian patients, phase 3 of the trial included 291 patients from both Asian and non-Asian countries.

Patients received either a combination of penpulimab and standard chemotherapy or a placebo plus chemotherapy. The study’s findings showed that patients who had penpulimab added to their treatment plan had their cancer controlled for 9.63 months on average, compared to just 7.00 months for those who did not. This represents a 55% reduction in the risk of disease progression. The researchers also found that the combination of penpulimab with chemotherapy had a manageable safety profile with tolerable side effects.

"What makes penpulimab unique is that it is an anti-PD-1 antibody with a modified structure designed to potentially improve efficacy while reducing immune-related side effects," said Dr. Shreenivas, who led at the study at City of Hope, one of 46 trial sites worldwide. "This research supports use of penpulimab plus chemotherapy as a new first-line treatment option for patients with recurrent or metastatic nasopharyngeal carcinoma."

He also says that since penpulimab has already been approved in China for some other cancers, like relapsed or refractory classic Hodgkin’s lymphoma and metastatic squamous non-small-cell lung cancer, this study might lead to expanded approvals for penpulimab in additional countries.

According to Dr. Shreenivas, future findings from the clinical trial could include explorations of how to identify which patients benefit most from this treatment, as the researchers analyzed various subgroups including those with liver metastases, different protein expression levels, and different DNA levels of Epstein-Barr virus, which is considered a strong risk factor for nasopharyngeal carcinoma.

The clinical trial was sponsored by Akeso, a Chinese biopharmaceutical company that developed penpulimab.

Researchers use innovative technologies to learn more about treatment responses on ovarian, prostate and breast cancer patients

Ovarian cancer

Not all patients with aggressive, high-grade serous ovarian cancer — the most common type of the disease — respond the same way to immunotherapy. To elucidate differences that might help tailor immunotherapy strategies for individual patients, a group of researchers from City of Hope and USC led by Jing Qian, a doctoral student in the lab of John D. Carpten, Ph.D., City of Hope’s chief scientific officer, Irell & Manella Cancer Center Director’s Distinguished Chair and Morgan & Helen Chu Director’s Chair of the Beckman Research Institute, sought to characterize the cancer and immune cells within the tumor environments of patients with different responses to treatment.

By using spatial transcriptomic technologies to map interactions between cancer and immune cells, the team was able to reveal differing immune cell behavior and composition in tumors with varied responses to immunotherapy. Spatial transcriptomic methods can provide valuable insights into gene expression within tissue and the technology is an area of rapid development in medical research.

"In the future, this approach could help identify patients who are more likely to benefit from immunotherapy and uncover new targets to improve treatment for those who don’t respond," said Qian. "Ultimately, it pushes the field closer to precision immuno-oncology in high-grade serous ovarian cancer."

Next, the team plans to use cell models and additional patient cohorts to explore whether targeting specific immune cell types can improve responses to immunotherapy in ovarian cancer.

Qian will present "Spatial transcriptomics reveals differences in the tumor and immune microenvironment of high-grade serous ovarian cancers with differing responses to immune checkpoint inhibitors" as a late breaking poster session on Sunday from 2:00 to 5:00 p.m. CT.

Prostate cancer

Recent studies suggest that a complex interplay between ethnicity and disease biology could influence how metastatic hormone sensitive prostate cancer (mHSPC) behaves in different patients. To investigate differences in tumor tissue from patients of Hispanic background compared to those not of Hispanic background, a team of City of Hope researchers led by Tanya Barauskas Dorff, M.D., professor in the Department of Medical Oncology & Therapeutics Research, borrowed pre-treatment prostate biopsy specimens from an existing clinical trial.

Using digital spatial profiling, a technology used to study gene and protein expression in tissues, the researchers were able to interrogate the tumor microenvironment from different patients with mHSPC with greater granularity and depth. They found a difference in expression of certain proteins like Foxp3, PARP and STING, all of which are targets of certain cancer medications, between Hispanic and non-Hispanic patients.

"This type of exploration in tissue samples from patients of diverse backgrounds may help uncover factors that could account for differences in treatment response," said Dr. Dorff. "As we complete the testing on additional tissue samples, we hope to compare results against treatment outcomes, to see a clearer signal emerge identifying candidate proteins for future validation."

She said the team hopes to increase the variety of samples being tested and compare their findings to clinical outcomes from the trial, which should become available early 2026.

Peter Zang, M.D., a hematology & oncology fellow and first author on "Digital spatial profiling with GeoMx to identify differential protein expression in Non-Hispanic/Latino and Hispanic/Latino Patients with metastatic hormone sensitive prostate cancer," will present the team’s poster abstract on Tuesday from 2:00 to 5:00 p.m. CT.

Breast cancer

A poster presentation by Sydney Grant, a postdoctoral fellow, and Aritro Nath, Ph.D., assistant professor in the Department of Medical Oncology & Therapeutics Research, on Tuesday from 9:00 a.m. to 12:00 p.m. CT, "Integrating multimodal data with survival-based variational autoencoders to predict recurrence-free survival in breast cancer," will highlight a powerful new AI-based approach the team developed to predict recurrence-free survival in breast cancer patients.

By enhancing existing generative AI models to process a broader range of real-world patient data, which extend far beyond traditional biomarkers currently used in the clinic, Grant and Nath established an approach that enables more accurate and personalized predictions about cancer patient outcomes.

"This work could lead to new clinical tests used at the time of diagnosis to guide treatment decisions and bring us closer to truly personalized care," said Dr. Nath. "For example, these tools would help doctors identify which patients need more aggressive therapy and which patients could avoid overtreatment and unnecessary side effects."

The team is now working to extend their models to predict which types of treatment or drug classes will work best for individual patients, with the goal of guiding therapy selection in the clinic using AI.

New technology identifies unique genetic changes in early-onset colorectal cancer among Hispanic and Latino patients

Colorectal cancer is the second leading cause of cancer-related deaths and cases among younger patients are rising, particularly among Hispanic and Latino populations. A new study from the lab of Enrique Velazquez Villarreal, M.D., Ph.D., M.P.H., M.S., assistant professor in the Department of Integrative Translational Sciences, has found that early-onset colorectal cancer in Hispanic and Latino patients has unique genetic changes that help explain how the cancer grows and spreads.

"This is the first study to look closely at the genetics of colorectal cancer in Hispanic and Latino patients from the Los Angeles area, a group that’s often left out of cancer research," said postdoctoral fellow Francisco (Paco) Carranza, who is first author on the study. "By understanding how colorectal cancer affects different populations, especially those who are often overlooked, we can help create better and more targeted treatments."

To find genetic changes, the research team used DNA and RNA sequencing plus a powerful new technology called 10x Genomics Visium that let them see which genes are turned on or off in specific parts of a tumor. This helped them better understand how cancer cells interact with the immune system and how the disease behaves in this patient population.

"This kind of research brings us closer to making sure all patients—no matter their background—have access to the best possible care and the same chance at successful outcomes," said Dr. Velazquez Villarreal, whose research is focused on addressing colorectal cancer health disparities in Hispanic and Latino communities.

Next, Carranza and his collaborators plan to move this research even closer to patient care by using an advanced version of the 10x Genomics Visium platform that allows researchers to look at tumors one cell at a time to give even more detailed information that could lead to better tailored therapies and help design new clinical trials.

Carranza will discuss the team’s work during a minisymposium session called "Multi-omics analysis of MYC gene and WNT signaling pathway alterations in early-onset colorectal cancer in Hispanic/Latino patients, enhanced with spatial transcriptomics approaches" on Monday from 2:35 to 2:50 p.m. CT.

AI tool developed at City of Hope makes precision medicine more accessible and inclusive

Dr. Velazquez Villarreal will also present a poster on his lab’s development of a new precision medicine AI tool that addresses key challenges in the integration of different data sets to promote better equity in cancer research.

The new tool, called the Precision Medicine Artificial Intelligence Agent (PM-AI), is a conversational AI system that can understand plain-language questions and automatically run complex data analyses. It combines clinical information, genetic data, and social factors like income or access to care to make it easier for scientists to study cancer in a more complete and inclusive way.

"By making it easier to analyze large and complex datasets, PM-AI can help researchers and doctors discover which treatments work best for different groups of people," said Dr. Velazquez Villarreal. This means patients could one day receive more personalized care based on their genetics, health history, and social conditions—leading to better outcomes for everyone, especially underserved communities."

He said the research team plans to keep expanding PM-AI’s capabilities by applying it to more types of cancer and integrating even more kinds of data. The goal is to support clinical decisions, help design new studies and ultimately make precision medicine more accessible for all patients.

The study, "PM-AI agent: A conversational artificial intelligence system for precision medicine and advancing health equity through integrative clinical, genomic and social determinants of health data analysis," is the first accepted by AACR (Free AACR Whitepaper) to use a cutting-edge technology known as an AI-driven conversational agent and will be presented during a poster session on Sunday from 2:00 to 5:00 p.m. CT.

Combination treatment found to overcome therapy resistance in ER+ breast cancer

In patients with estrogen receptor-positive (ER+) breast cancer — the most common type of the disease — 30-50% eventually develop resistance to primary endocrine therapy and progress to advance disease. While cell cycle inhibitor therapies help slow down metastatic ER+ breast cancer, patients often become resistant to these treatments, too.

Now, a new study by City of Hope researchers has revealed that ER+ breast cancers resistant to cell cycle inhibitors undergo dynamical rewiring of both apoptosis (or cell death) pathways and proliferative pathways, which regulate cell division and growth, to survive. To overcome this resistance, the team looked for add-on therapies that target growth factor receptors. Their goal was to find a combination that provides a blockade of proliferative pathways with sustained upregulation of apoptosis pathways to maintain treatment effectiveness.

Using leading-edge integration of short- and long-term biological experimentation cell models with mathematical and computational analysis, they discover a new proposed combination therapy of ribociclib (a cell cycle inhibitor) plus afatinib (a growth factor inhibitor) that can durably control breast cancer cell growth over time.

"Although cell growth-targeted drugs have improved outcomes for hormone-dependent breast cancer patients, resistance remains a major clinical challenge limiting their long-term benefit," said Andrea Bild, Ph.D., professor in the Department of Medical Oncology & Therapeutics Research and senior author of the study. "Our research presents a novel strategy to enhance the durability and effectiveness of current treatments."

Next, the research team aims to translate their findings for patient benefit in the clinic. To do so, Dr. Bild said they will expand their use of temporal computational and mathematical modeling to monitor molecular changes over time and identify dynamic biomarkers that can guide future treatment strategies.

Kimya Karimi, a doctoral student in Dr. Bild’s lab, will present the team’s study "Overcoming intrinsic mechanisms of cell cycle inhibitor resistance in estrogen receptor-positive (ER+) breast cancer" during a minisymposium on Tuesday from 3:05 to 3:20 p.m. CT.