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DESTINY-Ovarian01 Phase 3 Trial of ENHERTU® Initiated as FirstLine Maintenance Therapy in Patients with HER2 Expressing Advanced Ovarian Cancer

On December 9, 2025 Daiichi Sankyo reported that the first patient has been dosed in the randomization phase of the DESTINY-Ovarian01 phase 3 trial evaluating ENHERTU (trastuzumab deruxtecan) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab.

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DESTINY-Ovarian01 is being conducted in collaboration with the European Network of Gynecological Oncological Trial Groups (ENGOT), with the Spanish cooperative group (GEICO) as the lead ENGOT group, The GOG Foundation, Inc. (GOG-F) and Asia-Pacific Gynecologic Oncology Trials Group (APGOT).

ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

The prognosis for patients with ovarian cancer is poor with an estimated five-year survival rate of 31.8% for those with advanced disease.1 Approximately 70% to 80% of patients with advanced ovarian cancer (Stage 3 or 4) will experience disease recurrence following standard treatment with surgery and platinum-based chemotherapy regimens.2 Maintenance therapy may be given to delay relapse and current recommended treatment strategies include bevacizumab or PARP inhibitor monotherapy or bevacizumab/PARP inhibitor combination treatment, depending on the biomarker status of the tumor. 3 There currently are no HER2 directed medicines approved as maintenance therapy despite HER2 expression being present in up to 55% of ovarian cancers.

"Results from the ovarian cancer cohort of DESTINY-PanTumor02 demonstrated clinically meaningful and durable responses in previously treated patients with HER2 expressing advanced ovarian cancer, supporting the development of ENHERTU in earlier lines of therapy," said Abderrahmane Laadem, MD, Head, Late- 2 Stage Oncology Clinical Development, Daiichi Sankyo. "Given the important role first-line maintenance therapy can play in disease control, we have initiated this first phase 3 trial in ovarian cancer to evaluate whether ENHERTU combined with bevacizumab could become a new maintenance strategy for patients with HER2 expressing advanced high-grade epithelial ovarian cancer."

About DESTINY-Ovarian01

DESTINY-Ovarian01 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) in combination with bevacizumab versus bevacizumab monotherapy as first-line maintenance therapy in patients with HER2 expressing (IHC 3+/2+/1+) advanced high-grade epithelial ovarian cancer following treatment with first-line platinum-based chemotherapy in combination with bevacizumab. The randomized period of the trial was preceded by a non-randomized safety run-in phase to evaluate the safety of ENHERTU in combination with bevacizumab.

The primary endpoint is progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the HER2 IHC 3+/2+ population. The key secondary endpoint is overall survival (OS) in the HER2 IHC 3+/2+ population. Additional secondary endpoints include PFS as assessed by BICR and OS in the HER2 IHC 3+/2+/1+ population as well as PFS as assessed by investigator in both the HER2 IHC 3+/2+ and HER2 IHC 3+/2+/1+ populations.

DESTINY-Ovarian01 will enroll approximately 580 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov

About Ovarian Cancer

Ovarian cancer is the third most common gynecologic cancer and the seventh most common cancer among women worldwide. 7 More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.8 The prognosis for ovarian cancer is poor with an estimated five-year survival rate of 31.8% for those with advanced disease.1 Epithelial ovarian cancer accounts for approximately 90% of ovarian cancer cases and the majority are diagnosed at an advanced stage (Stage 3 or 4).

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors.10 HER2 expression (IHC 3+/2+/1+) is present in up to 55% of ovarian cancers and is associated with advanced stages, higher frequency of recurrence, shorter survival time and lower response to platinum-based chemotherapy.

Approximately 70% to 80% of patients with advanced ovarian cancer (Stage 3 or 4) will experience disease recurrence following standard treatment with surgery and platinum-based chemotherapy regimens.2 Maintenance therapy may be given to delay relapse and current recommended treatment strategies include 3 bevacizumab or PARP inhibitor monotherapy or bevacizumab/PARP inhibitor combination treatment, depending on the biomarker status of the tumor. 3 As a majority of patients will experience disease progression on or after these therapies, new treatment strategies are needed. 12,13,14,15 Currently, there are no HER2 targeted medicines approved as first-line maintenance therapy for patients with HER2 expressing advanced epithelial ovarian cancer.

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization [ISH]+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4 mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH- ) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

ENHERTU (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (5.4 mg/kg) is approved in more than 10 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the ENHERTU Clinical Development Program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable cancers.

(Press release, Daiichi Sankyo, DEC 9, 2025, View Source [SID1234665025])

Termination of a Material Definitive Agreement.

On December 9, 2025, GlaxoSmithKline Intellectual Property (No. 4) Limited ("GSK") delivered written notice to IDEAYA Biosciences, Inc. (the "Company") of its election to terminate the Collaboration, Option and License Agreement, dated June 15, 2020 (as amended, the "Agreement"). This written notice constituted GSK’s formal written follow-up to its December 4 communication to the Company regarding the termination, as referenced in the Company’s Form 8-K filed on December 5, 2025. Pursuant to the terms of the Agreement, such termination will be effective ninety (90) days following the date of GSK’s notice, which is March 9, 2026. During the ninety-day transition period, GSK will transfer the Werner Helicase (IDE275) and Pol Theta (IDE705) clinical programs to the Company in accordance with the applicable provisions of the Agreement. The Company will evaluate its strategic options for these two programs in 2026, and the update does not change its expectation of cash runway into 2030.

The Agreement is filed as Exhibit 10.3 to the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 12, 2020, Exhibit 10.18 to the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 18, 2022 and Exhibit 10.3 to the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 10, 2022. For a summary of the material terms of the Agreement, please see Note 10, Significant Agreements, to Company’s financial statements for the Company’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission on February 18, 2025, which summary is incorporated by reference herein.

(Filing, 8-K, Ideaya Biosciences, DEC 9, 2025, View Source [SID1234661403])

BriaCell’s Phase 3 Patient Enrollment on Track for 1H2026 Topline Data Readout

On December 9, 2025 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company developing novel immunotherapies to transform cancer care, reported its Phase 3 clinical study has screened over 230 and enrolled over 160 patients. BriaCell anticipates reporting topline data as early as 1H2026.

Interim data will be analyzed once 144 patient events (deaths) occur. Positive results from this pivotal study could support full approval and marketing authorization of Bria-IMT in patients with metastatic breast cancer.

BriaCell’s pivotal Phase 3 clinical study is evaluating BriaCell’s lead clinical candidate, Bria-IMT, plus an immune check point inhibitor versus physician’s choice in a dvanced metastatic b reast c ancer (Bria-ABC).

"The pace of patient enrollment in our pivotal Phase 3 study has exceeded expectations underscoring the strong engagement of participating sites and the high level of interest from patients and investigators," stated Dr. William V. Williams, BriaCell’s President & CEO. "We look forward to collecting, analyzing and sharing the Phase 3 data with the U.S. FDA in the coming months as we continue working to bring hope to patients with metastatic breast cancer who face an urgent medical need."

About BriaCell’s Pivotal Phase 3 Clinical Study of Bria-IMT Combination Regimen in MBC patients

BriaCell’s pivotal Phase 3 study of Bria-IMT plus an immune check point inhibitor (CPI) in metastatic breast cancer is ongoing.

Interim data from BriaCell’s ongoing pivotal Phase 3 study of Bria-IMT plus an immune check point inhibitor in metastatic breast cancer will be analyzed once 144 patient events (deaths) occur. This interim analysis will assess overall survival (OS) as the primary endpoint, comparing patients treated with the Bria-IMT combination regimen to those receiving physician’s choice therapy. Positive results from this pivotal study could support full approval and marketing authorization of Bria-IMT in patients with metastatic breast cancer. The Bria-IMT combination regimen has been granted FDA Fast Track designation.

For additional information on BriaCell’s pivotal Phase 3 study, please visit ClinicalTrials.gov NCT06072612.

(Press release, BriaCell Therapeutics, DEC 9, 2025, View Source [SID1234661341])

Study Establishes Molecular Link Between Tumor Metabolism and Drug Engagement in Cancer Cells

On December 9, 2025 Promega reported a new study published in Nature Communications reveals technological advances that accelerate breakthroughs in precision medicine. Conducted as a collaboration between Promega, the Center for Advanced Study of Drug Action at the State University of New York at Stony Brook, and the Centre for Medicines Discovery at the University of Oxford, the work leverages bioluminescent NanoBRET Target Engagement (TE) technology developed by Promega to characterize inhibitors that selectively target cancer cells without harming noncancerous cells. Their results demonstrate a connection between drug efficacy and tumor metabolic state, offering a mechanistic bridge between cancer metabolism and precision oncology.

"To our knowledge, this is the first time anyone has characterized this type of uncompetitive inhibitor mechanism directly in live cells." -Ani Michaud, Sr Research Scientist at Promega

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"The methods in this study enable us to characterize inhibitors that bind much more tightly in tumor cells with specific mutations," says Ani Michaud, Sr Research Scientist at Promega and co-first author of the Nature Communications paper. "To our knowledge, this is the first time anyone has characterized this type of uncompetitive inhibitor mechanism directly in live cells."

PRMT5: Top Target for Drug Discovery

The published study focuses on a gene-regulating protein called PRMT5, which has long been considered a top target for drug discovery. In normal cells, PRMT5 interacts with a molecule called SAM. However, in the tumor cells of approximately 10-15% of cancers, a deletion of the MTAP gene leads to PRMT5 interacting with the molecule MTA instead, reducing its function. This difference creates a key vulnerability for targeting cancer cells with a mutation to MTAP while leaving normal cells unaffected.

The University of Oxford team designed and developed CBH-002, a cell-permeable BRET probe that binds to a genetically encoded PRMT5-NanoLuc biosensor to report drug target engagement in live cells.

Dr Elisabeth Mira Rothweiler, Postdoctoral Researcher, Centre for Medicines Discovery, University of Oxford and co-first author, says: "CBH-002 could measure various PRMT5 inhibitor types in live cells, prompting us to test its sensitivity to the cofactor SAM. When we discovered the probe’s ability to sense metabolite levels, it established its utility as a metabolic biosensor. Through collaboration with Promega, we demonstrated how MTA influences drug selectivity, revealing why certain inhibitors are so effective in MTAP-deleted cancers."

Dr Rothweiler’s research further enables a strategy for developing molecules that exploit the metabolic vulnerabilities specific to MTAP-deleted cancers, potentially offering highly targeted treatments with minimal effects on healthy tissue.

Uncompetitive Binding in Live Cells

While past studies have characterized this mechanism-of-action (MoA) in biochemical assays, this is the first to use NanoBRET TE technology to characterize uncompetitive, or cooperative, binding in live cells. Biochemical assays can reveal uncompetitive MoAs, but there is often a discrepancy between biochemical data and functional assays like selective cell killing. The NanoBRET TE assay used in this study bridges the two modalities, showing binding MoA in a cellular context that aligns with functional assay results.

Professor Kilian Huber, Associate Professor, Centre for Medicines Discovery, University of Oxford and co-senior author of the study, says, "The biosensor lets us examine, in living cells, how different PRMT5 inhibitors behave under the specific metabolic conditions that make some tumors uniquely vulnerable. This provides unprecedented insight into why certain inhibitors are much more effective in cancers lacking MTAP and paves the way for highly targeted cancer treatment in the future. It’s like turning on the lights inside the cell so we can finally see which key actually fits the lock."

"Selectivity is one of the most critical challenges in cancer therapy, as most treatments also damage healthy cells, leading to dose-limiting toxicities and reduced therapeutic effectiveness," says Peter Tonge, distinguished professor of chemistry and director of the Center for Advanced Study of Drug Action at the State University of New York at Stony Brook and visiting professor at the University of Rochester. "A new class of tumor-specific drugs addresses this by acting uncompetitively with a metabolite that accumulates only in cancer cells, limiting activity to tumor tissue. We have now developed the first technology to quantify the activity of these drugs directly in live cells, providing a foundation for optimizing and advancing next-generation precision oncology therapeutics."

Collaboration Between Academia and Industry

This study was the result of collaboration between Promega, the Center for Advanced Study of Drug Action at the State University of New York at Stony Brook, and the Centre for Medicines Discovery at the University of Oxford, with additional contributions from researchers at Boston University and the Structural Genomics Consortium at the University of Toronto.

"This work underscores the value of research collaborations between academia and industry," says Matt Robers, Associate Director of R&D at Promega and co-senior author of the study. "By combining our complementary expertise in chemical biology and assay design, we were able to dissect how cooperativity can drive cancer cell selectivity. These findings have real potential to guide the development of future precision medicines."

Read the paper "A BRET biosensor for measuring uncompetitive engagement of PRMT5 complexes in cells" in Nature Communications here: View Source

(Press release, Promega, DEC 9, 2025, View Source [SID1234661337])

Natera Highlights New Findings in Lymphoma at the ASH Annual Meeting

On December 9, 2025 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, reported the results from two oral presentations that were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Real-world Signatera Analysis: Oral Presentation on December 6

A real-world analysis of personalized circulating tumor DNA (ctDNA) detection in lymphoma evaluated 144 patients across 14 lymphoma subtypes, including aggressive and indolent lymphomas and patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy. Signatera was used clinically to assess baseline ctDNA detection, track molecular clearance during first-line (1L) therapy, and evaluate end-of-treatment (EOT) ctDNA status and post-CAR-T response. Key findings included:

Across 14 subtypes of lymphoma, 94% of patients had detectable ctDNA in a pre-treatment sample.
ctDNA clearance during treatment was highly predictive of CAR-T response (p = 0.0028).
Rapid ctDNA clearance after one cycle of chemotherapy was more predictive of positive outcomes vs. delayed clearance after two cycles of therapy (HR: 20.95 vs. 7.45).
Signatera status at the end of 1L therapy was highly prognostic of event-free survival (HR: 49.77, p<0.0001), outperforming standard of care PET-CT response assessment across lymphoma subtypes.
HOVON Study: Oral Presentation on December 7

The HOVON study was conducted by Foresight Diagnostics, a subsidiary of Natera, in collaboration with Amsterdam University Medical Centers, the Hemato-Oncology Foundation for Adults in the Netherlands (HOVON) and the Netherlands Comprehensive Cancer Organization (IKNL). The study evaluated longitudinal molecular residual disease (MRD) surveillance in 166 patients with diffuse large B-cell lymphoma. The study provided one of the most detailed evaluations to date of ctDNA-MRD dynamics over a two-year surveillance period using the CLARITY ctDNA assay. Key findings included:

The CLARITY ctDNA assay showed early molecular response was associated with improved clinical outcomes, demonstrating its utility as an early risk-stratification marker.
Following any negative ctDNA test during surveillance, the probability of remaining relapse-free was 99% at 6 months and 97% at 12 months.
Early on-treatment molecular response could serve as a dynamic marker for therapy de-escalation or escalation trials, enabling adaptive trial designs.
"These presentations highlight the value of ctDNA in assessing treatment response and long-term risk across lymphoma subtypes, including diffuse large B-cell lymphoma," said Minetta Liu, M.D., chief medical officer of oncology and early cancer detection at Natera. "The findings reinforce how the detection of disease at the molecular level can support more personalized treatment and surveillance strategies for patients with cancer."

(Press release, Natera, DEC 9, 2025, View Source [SID1234661336])