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Iterion Therapeutics Reports First Clinical Validation of Tegavivint as a Targeted Therapy for Wnt-Driven Advanced HCC in Oral Presentation at 2026 ASCO Annual Meeting

On June 1, 2026 Iterion Therapeutics, a clinical-stage biopharmaceutical company dedicated to advancing the treatment of Wnt-driven cancers, reported positive initial data from the dose-escalation portion of its ongoing Phase 1/2 study evaluating tegavivint in patients with advanced HCC. The data will be shared in a rapid oral presentation titled "Tegavivint, a downstream Wnt/b-catenin inhibitor: Dose-finding results from a phase 1/2 trial in advanced hepatocellular carcinoma (aHCC)," at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and will be featured by David Hsieh, M.D., Associate Professor at UT Southwestern Medical Center.

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Tegavivint is a first-in-class, clinical-stage downstream Wnt/β-catenin inhibitor designed to disrupt the TBL1:β-catenin transcriptional activation complex, promote nuclear β-catenin degradation, and block oncogenic transcription in Wnt-driven tumors.

"These data provide important clinical validation of tegavivint’s mechanism as a downstream inhibitor of Wnt/β-catenin signaling and support its development as a targeted therapy in HCC and other Wnt-driven cancers," said Rahul Aras, Ph.D., President and CEO of Iterion Therapeutics. "We are particularly encouraged by the depth and durability of monotherapy responses observed in heavily pretreated patients, and by the concentration of clinical benefit in a molecularly selected population of patients with Wnt-pathway activating mutations".

Key Findings from the Study

A total of 40 patients were enrolled. Patients had received a median of two prior lines of systemic therapy, and 29 patients (73%) had tumors with WPAMs, including alterations in AXIN1, CTNNB1, CREBBP, and APC, as assessed by ctDNA testing.

Tegavivint was generally well tolerated across dose levels. Treatment-related adverse events (TRAEs) occurred in 27 of 40 patients (68%) and were mostly Grade 1 or 2, with fatigue, hyperbilirubinemia, anemia, decreased appetite, and myalgia as the most common TRAEs. Grade 3 anemia at the 8 mg/kg dose level was dose-limiting but reversible, supporting a recommended dose range of 3 to 6.5 mg/kg.

Clinical activity among efficacy-evaluable patients treated with tegavivint at the recommended dose range was observed primarily in patients with WPAM+ tumors:

Tegavivint produced tumor shrinkage in approximately 40% of evaluable patients with WPAM+ tumors and achieved a 72% disease control rate (DCR); no tumor shrinkage was observed in patients without WPAMs.
In second- and third-line patients with WPAM+ tumors, tegavivint achieved a 22% overall response rate (ORR), an 89% DCR and a median progression-free survival (mPFS) of 8 months.
Paired tumor assessments showed reductions in active b-catenin protein levels following tegavivint treatment. Dose-proportional decreases in alpha-fetoprotein (AFP) and reductions in WPAM ctDNA variant allele frequency were also observed.
"Patients with advanced HCC whose tumors harbor Wnt/β-catenin pathway mutations represent a large, genetically defined population with significant unmet need and no approved targeted therapy targeting this biology," said David Hsieh, M.D., Associate Professor at UT Southwestern Medical Center and presenting author of the study. "The clinical activity observed with tegavivint is encouraging and supports further development of this investigational therapy as a potential novel treatment option for biomarker-selected patients."

About Tegavivint

Tegavivint is a potent and selective first-in-class small molecule designed to inhibit the downstream Wnt/b-catenin signaling pathway by binding to TBL1. By disrupting the nuclear TBL1:b-catenin complex, tegavivint is designed to promote degradation of nuclear b-catenin and inhibit expression of genes that drive tumor growth, survival and resistance to therapy in multiple cancer types, while sparing cytoplasmic and membrane-bound b-catenin pools that are necessary for normal cellular function.

(Press release, Iterion Therapeutics, JUN 1, 2026, View Source [SID1234666331])

Cancer Vaccine Sustains 49 Percent Melanoma Reduction After 5 Years

On June 1, 2026 NYU Langone Health reported the combination of a vaccine and a drug, which both harness the immune system to attack cancer cells, has proven successful in cutting the risk of skin cancer recurrence and death by 49 percent, a new study shows. This reduction was calculated five years after patients had their tumors surgically removed and remains unchanged.

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the study tested the vaccine, called intismeran, in combination with mainstay immunotherapy pembrolizumab (Keytruda) in 107 patients who had been randomly chosen after melanoma surgery to determine whether the combination therapy prevented their cancer from recurring. Intismeran is a personalized immunotherapy strategy that is developed with information from a patient’s individual tumor. These results were compared with those from a randomly selected group of 50 melanoma patients who had only received pembrolizumab postoperatively, a current standard of care.

Results of the phase 2b trial, known formally as KEYNOTE-942, are being presented at the 2026 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) on June 1 in Chicago, and simultaneously published in the society’s Journal of Clinical Oncology.

After five years of follow-up, 68.8 percent of patients who took the combination therapy remained cancer free while 49.1 percent of the patients in the pembrolizumab-alone group had no signs of cancer This means that adding intismeran to pembrolizumab reduced the risk for recurrence or death by 49 percent. The combination therapy also reduced the risk of distant metastasis — the spread of cancer to another part of the body — by 59 percent. Overall survival, meaning no death from cancer or any other cause, was 92.2 percent for the vaccine with immunotherapy group, while for the immunotherapy-alone group it was 71.3 percent.

"Our study offers strong evidence to melanoma patients that intismeran vaccine therapy, when used in combination with immunotherapy, can demonstrably reduce their risk of having their cancer return and improve clinical outcomes," said study senior investigator Janice Mehnert, MD, a professor in the Department of Medicine at NYU Grossman School of Medicine.

"Our findings also serve as encouragement to cancer researchers globally that mRNA vaccines like intismeran could work well in combination with immunotherapy for other cancers whose high rates of mutations have proven difficult to target," said Dr. Mehnert, who also serves as director of the melanoma medical oncology program and associate director of clinical research at Perlmutter Cancer Center.

The study results highlight the role of T cells, which are capable of attacking viruses as well as cancers. To spare normal cells, the immune system uses checkpoint molecules on T cell surfaces to "turn off" their attack against viruses when they clear the infection. The body may recognize tumors as abnormal, but cancer cells hijack checkpoints to turn off and evade immune responses. Immunotherapies like pembrolizumab seek to block checkpoints, specifically the PD-1 protein receptor, making cancer cells more "visible" and vulnerable again to immune cells.

Immunotherapies, such as PD-1 inhibitors like pembrolizumab, have become the mainstay for treating melanoma, although they do not work for all patients because melanoma cells, known for their ability to evade the immune system, can become resistant to immunotherapy. For this reason, researchers have looked at adding vaccines.

The vaccine intismeran is based on messenger RNA, a chemical cousin of DNA that provides cells with instructions for making proteins. Intismeran and other mRNA cancer vaccines are meant to teach the immune system to recognize cancer cells as different from normal cells. In designing a vaccine against melanoma, researchers attempted to trigger an immune response to specific abnormal proteins, called neoantigens, made by cancer cells.

Because the study volunteers all had their tumors removed, researchers were able to analyze their cells for 34 neoantigens that were specific to each melanoma and create a personalized vaccine for each patient. As a result, T cells specific to the neoantigen proteins encoded by the mRNA were produced. Those T cells could then attack any melanoma cells trying to grow or spread.

Dr. Mehnert said that a phase 3, multicenter trial is already underway to determine if intismeran helps as a firstline therapy in combination with pembrolizumab for melanoma. Already, the vaccine is being tested to see if it also works to prevent recurrence of lung and other cancers.

For the KEYNOTE-942 trial, patients were enrolled at cancer centers in Australia and the United States from 2019 to 2021. All were men and women who had had surgery to remove their melanoma tumors. Seven patients in each treatment group died during follow-up, most from cancer. Side effects were considered manageable and included fatigue, pain at injection sites, and chills.

Cancer of the skin is the most common form of cancer in the United States, with an estimated 112,000 new cases in 2026 (about 65,400 in men and 46,600 in women). Melanoma deaths have declined sharpy in the past decade, largely due to advances in treatment.

Funding support for this study was provided by Moderna Inc. in Cambridge, Massachusetts, the manufacturer of intismeran, and Merck & Co. in Rahway, New Jersey, the manufacturer of pembrolizumab.

Besides Dr. Mehnert, researchers involved in this study were lead investigator Adnan Khattak, MD, PhD, at Hollywood Private Hospital and Edith Cowan University, in Perth, Australia; co-investigators Matteo Carlino, MD, PhD, and Georgina Long, MD, PhD, at the University of Sydney in Australia; Tarek Meniawy, PhD, at Saint John of God Hospital Subiaco Hospital in Subiaco, Australia; George Ansstas, MD, at Washington University in St. Louis; Matthew Taylor, MD, at the Providence Cancer Institute in Portland, Oregon; Kevin Kim, MD, at the California Pacific Medical Center Research Institute in San Francisco; Meredith McKean, MD, at the Sarah Cannon Research Institute in Nashville; Ryan Sullivan, MD, at the Mass. General Brigham Cancer Institute and Harvard University in Boston; Mark Faries, MD, at the Angeles Clinic and Research Institute, a Cedars-Sinai affiliate in Los Angeles; Thuy Tran, MD, PhD, at the Smilow Cancer Center at Yale New Haven Hospital in Connecticut; Lance Cowey, MD, at Texas Oncology PA in Dallas; Andrew Pecora, MD, at Hackensack University Medical Center in New Jersey; Theresa Medina, MD, at the University of Colorado Cancer Center in Aurora; Victoria Atkinson, MD, at Princess Alexandra Hospital in Brisbane; Clemens Krepler, PhD, and Lthomas Jemielita, PhD, at Merck; and Huzhang Mao, MD, Jacky Chow, PhD, and Laureen Ojalvo, MD, PhD, at Moderna.

(Press release, NYU Langone Health, JUN 1, 2026, View Source [SID1234666330])

Sonire Therapeutics Completes Enrollment in SUNRISE-I Randomized Controlled Trial of Ultrasound-Guided HIFU Therapy for Pancreatic Cancer

On June 1, 2026 Sonire Therapeutics, a U.S.-based clinical-stage medical device company, reported the completion of patient enrollment in SUNRISE-I, a randomized controlled trial evaluating the safety and efficacy of its proprietary High-Intensity Focused Ultrasound (HIFU) therapy system for the treatment of pancreatic cancer.

This multi-center study was conducted across seven leading clinical sites in Japan with a total of 90 patients with overall survival (OS) as the primary endpoint. The study represents one of the few randomized controlled trials (RCTs) conducted in the HIFU space for pancreatic cancer treatment, one of the most intractable cancers in the world today.

"Patients facing pancreatic cancer need treatment options that are less invasive, more accessible, and easier to integrate into real-world clinical practice," said Tohru Satoh, President and CEO of Sonire Therapeutics. "SUNRISE-I reflects our efforts to develop treatment approaches that reduce the burden on patients and address some of the limitations of existing treatment options. We believe the future of oncology will be shaped by therapies that are better suited to the needs of both patients and healthcare providers."

Sonire’s HIFU therapy system leverages real-time ultrasound guidance to deliver precise, non-invasive tumor ablation, allowing physicians to monitor treatment as it is administered without the need for general anesthesia. The approach is designed to reduce the procedural burden while expanding access to treatment in outpatient settings.

SUNRISE-I forms the basis of Sonire’s ongoing U.S.-based clinical development program, including SUNRISE-II, which is currently evaluating the company’s HIFU system in the United States. Together, these studies form a global clinical strategy aimed at advancing minimally invasive treatment options for pancreatic cancer.

Atsushi Sofuni, MD, Professor of Gastroenterology at Tokyo Medical University and physician who treated the first patient in the SUNRISE-I study, said, "Pancreatic cancer remains one of the most difficult cancers to treat, with a significant unmet medical need. HIFU therapy represents an innovative approach that is distinct from existing treatments. We hope the SUNRISE-I study will contribute to expanding future treatment options for patients with pancreatic cancer."

"The completion of enrollment in SUNRISE-I is a step forward for the broader field exploring ultrasound-based approaches for pancreatic cancer treatment and highlights the growing clinical interest in advancing new therapeutic options for patients," said Pejman Ghanouni, MD, PhD, Principal Investigator of Sonire Therapeutics’ U.S.-based SUNRISE-II study. Ghanouni is also a Professor of Radiology at Stanford Medicine.

By generating the clinical evidence from randomized, multi-center clinical trial with overall survival as a primary endpoint, Sonire aims to strengthen the body of data supporting the safety and efficacy of its HIFU platform and advance toward future regulatory submissions and global commercialization.

(Press release, SONIRE Therapeutics, JUN 1, 2026, View Source [SID1234666329])

Promising Phase 1 Data for Servier’s Emiltatug Ledadotin (Emi-Le) in Adenoid Cystic Carcinoma (ACC) Presented at ASCO 2026

On June 1, 2026 Servier reported promising new Phase 1 clinical data for Emi-Le, an investigational antibody drug conjugate (ADC) directed against B7-H4, during an oral session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2026 Annual Meeting in Chicago, Illinois.

Emi-Le is an advanced engineered ADC that is directed against B7-H4, an immune checkpoint protein that is highly expressed in ACC along with several other cancers. As part of an ongoing Phase 1 trial, a dose escalation and backfill cohort enrolled adult patients with advanced or metastatic solid tumors (n=180), including those with ACC (n=48) defined by an aggressive clinicopathologic phenotype and/or molecular features consistent with poor prognosis.

"Emi-Le represents a novel, targeted therapeutic approach for patients who suffer from recurrent, advanced or metastatic ACC. The recent FDA Breakthrough Designation further validates the critical unmet need for a targeted systemic therapy to address the challenging effects of this disease for affected individuals," said Elly Barry, MD, Chief Medical Officer, Day One Biopharmaceuticals, now part of Servier Group. "These encouraging data at ASCO (Free ASCO Whitepaper) indicate strong promise to support a population distinctly in need of effective therapies and will help inform the pivotal Phase 2 study we will undertake in a larger set of participants."

The analysis presented at ASCO (Free ASCO Whitepaper) found:

Emi-Le was well-tolerated demonstrating a distinct and potentially differentiated emerging safety profile:
Most treatment-related adverse events (TRAEs) were transient laboratory-based and/or low-grade. The most common TRAEs were transient AST increase (56%) generally asymptomatic and reversible proteinuria (54%), predominantly low-grade fatigue (42%) and nausea (33%).
The only Grade 3 TRAEs in ≥10% of pts were transient AST increase (20%) and proteinuria (23%). No Grade 4 or 5 TRAEs reported.
TRAEs leading to treatment discontinuation occurred in 3.9% of patients and no treatment-related deaths were reported.
Promising signals of efficacy among 45 evaluable participants with ACC.
Objective response rate (ORR) was 35.6%, including one complete response.
Disease control rate was 82.2%.
Further, a post-hoc analysis was conducted in a more clearly defined aggressive ACC subtype reflecting clinical features used in practice by clinicians and pathologists, including solid histology or high-grade transformation. This analysis (n=32 evaluable participants) reported promising signals:
Consistent tumor shrinkage, with an ORR of 46.9%, DCR of 81.3% and median PFS of 7.8 months.
"These data provide important insights into the use of a targeted ADC for the difficult-to-treat rare cancer ACC, most notably demonstrating favorable tolerability and a potentially differentiated safety profile," said Glenn J. Hanna, M.D., study investigator and Director, Center for Cancer Therapeutic Innovation at Dana Farber Cancer Institute. "The encouraging anti-tumor activity observed to date supports continued investigation of this program, particularly given the poor prognosis for patients with ACC and the lack of approved or preferred systemic therapies in the advanced or metastatic setting. If confirmed in further studies, this profile could potentially represent a paradigm shift in treatment."

(Press release, Servier, JUN 1, 2026, View Source [SID1234666328])

IDEAYA Biosciences and Servier Provide Complete Data from Phase 2/3 Registrational OptimUM-02 Trial of the Darovasertib Combination in First Line HLA*A2:01 Negative Metastatic Uveal Melanoma in a Late-Breaking Oral Presentation at ASCO

On June 1, 2026 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, and Servier, an independent international pharmaceutical group governed by a foundation, reported complete data from the primary analysis of their registrational Phase 2/3 OptimUM-02 trial of darovasertib in combination with crizotinib (darovasertib combination) in first line (1L) HLA*A2:01 negative metastatic uveal melanoma (mUM) at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, Illinois. The data were provided in a late-breaking oral presentation by Dr. Marlana Orloff, M.D., Professor of Medical Oncology at Thomas Jefferson University Hospital and lead investigator on the trial. A copy of the presentation will be available on IDEAYA’s corporate website.

"The data from OptimUM-02 represent an exciting step forward in the treatment landscape for metastatic uveal melanoma, particularly for patients with HLA*A2:01 negative disease who have no approved treatment options," said Dr. Orloff. "The darovasertib combination drove consistent, robust and clinically meaningful improvements in response rate and progression free survival relative to checkpoint inhibitors that are commonly used today and supports its potential as a new therapeutic standard for patients with this devastating disease."

OptimUM-02 is a global, registrational Phase 2/3 trial evaluating a total of 313 patients with 1L HLA*A2:01 negative mUM, randomized 2:1 to the darovasertib combination or an investigator’s choice of therapy (ICT) arm reflective of real-world clinical practice that included ipilimumab plus nivolumab (anti-CTLA-4/PD-1) or pembrolizumab (anti-PD-1). The primary endpoint to support accelerated approval is median progression-free survival (PFS) as assessed by blinded independent central review (BICR). Secondary endpoints include safety and investigator assessed PFS, overall response rate (ORR), disease control rate (DCR) and duration of response. Data presented at ASCO (Free ASCO Whitepaper) were as of a cutoff date of January 23, 2026 and included additional detail on baseline characteristics as well as safety, secondary endpoints and median PFS across patient subgroups.

Key Findings from OptimUM-02

Primary endpoint (Phase 2 portion): progression free survival by BICR
The trial met the primary endpoint, with patients treated with the darovasertib combination demonstrating a statistically significant improvement in median PFS of 6.9 months versus 3.1 months in the ICT arm by BICR (HR: 0.42; 95% CI: 0.30, 0.59; p-value: <0.0001).
Patients treated with the darovasertib combination also had a statistically significant improvement in median PFS of 6.7 months versus 2.7 months for ICT by investigator assessment (HR: 0.36; 95% CI: 0.26, 0.50, p-value: <0.0001).
Notably, the darovasertib combination reduced the risk of disease progression by 58% and 64% as assessed by BICR and investigator assessment, respectively.
Treatment with the darovasertib combination demonstrated a consistent and meaningful improvement in median PFS relative to the ICT arm across a broad range of patient subgroups, including age and gender, type of immune therapy used in ICT, LDH stratification, ECOG status and site of metastasis.
Secondary endpoints: ORR, DCR, duration of response
Patients treated with the darovasertib combination had an ORR of 37.1% (78/210) and 39.5% (83/210) as assessed by BICR and investigator, respectively, compared to 5.8% (6/103) and 1.9% (2/103) in the ICT arm (p-value: <0.0001).
The darovasertib combination led to a disease control rate of 73.3% (154/210) and 74.3% (156/210) by BICR and investigator assessment, respectively, compared to 31.1% (32/103) and 27.2% (28/103) in the ICT control arm.
The median duration of response was 6.8 months (95% CI: 5.5, 11.3) by BICR and 6.8 months (95% CI: 4.8, 9.7) by investigator assessment based on a median follow-up time of 7.4 months as of the cutoff date.
Overall survival (Primary endpoint of the Phase 3 portion)
As noted in the topline results, data on overall survival (OS) was still immature as of the cutoff date, however, there was an early trend in OS improvement in the darovasertib combination arm relative to the ICT arm.
IDEAYA will provide the next OS update as part of the pre-specified interim analysis. Overall survival data, when available, will be used to support a potential full approval in the United States and globally.
Safety
The darovasertib combination was generally well-tolerated with a manageable safety profile consistent with previous results and known side-effects of each agent alone.
Median relative dose intensities of darovasertib and crizotinib were 91.0% and 77.1%, respectively, compared to 100% for the ICT arm.
Grade 3/4 treatment-related adverse events (TRAEs) occurred in 40.6% (97/239) of patients in the darovasertib combination arm compared to 37.0% (37/100) of patients in the ICT control arm.
Treatment-related serious adverse events (TR-SAE) were 9.2% (22/239) and 25.0% (25/100) in the darovasertib combination and ICT arms, respectively.
Low discontinuation rate due to TRAEs for darovasertib (2.5%) and crizotinib (10.0%) relative to ICT (19.0%).
The most common Grade 3/4 TRAEs included diarrhea (10.0%), syncope (7.1%) and hypotension (3.8.%) in the darovasertib combination arm compared to elevated liver enzymes (ALT, 7.0% / AST, 7.0%), diarrhea (6.0%), hepatitis (5.0%) and colitis (4.0%) in the ICT control arm.
In April 2026, IDEAYA announced the U.S. Food and Drug Administration (FDA) has agreed to review their new drug application (NDA) for darovasertib in combination with crizotinib under the Oncology Center of Excellence Real-time Oncology Review (RTOR) program. This program allows applicants to pre-submit components of their NDA to allow the FDA to review clinical trial data before the complete filing is submitted and aims to provide a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. IDEAYA completed its first pre-submission in May and expects to complete the NDA filing in the second half of 2026.

(Press release, Ideaya Biosciences, JUN 1, 2026, View Source [SID1234666327])