On December 10, 2025 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, together with Alliance Foundation Trials, LLC (AFT) and the Austrian Breast and Colorectal Cancer Study Group (ABCSG), reported initial translational research results from the international randomized Phase III PALLAS study.

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Presented today at the San Antonio Breast Cancer Symposium (SABCS), these first data, generated from a U.S. biomarker cohort of 420 patients, show that molecular residual disease (MRD) status, measured by the Signatera Genome test after surgery (and adjuvant chemotherapy +/- radiation if administered), is a highly prognostic biomarker for distant recurrence risk in stage II–III, HR+/HER2- breast cancer. The findings support Natera’s strategy to integrate MRD testing into routine post‑surgical risk assessment, enabling a more personalized approach to managing early-stage HR+ breast cancer. Data from a parallel ex-US cohort will be presented in conjunction with a treatment subgroup analysis at a later date.

In PALLAS, patients with stage II–III HR+/HER2- breast cancer were randomized to receive two years of palbociclib, a CDK4/6 inhibitor, in combination with endocrine therapy. Signatera MRD assessments were performed after surgery at three key postoperative timepoints: on the first day of protocol-directed experimental therapy (baseline), on-treatment at approximately 6 months (C6D1), and at the end of the 2-year interventional treatment period (EOT). Key findings from this initial analysis include:

Signatera correctly identified patients with low risk of recurrence.

At baseline, approximately 92% of patients were MRD-negative and had excellent outcomes, with 5-year distant recurrence-free interval (DRFI) of 93%. Measured starting at EOT, MRD-negative patients had a 5-year DRFI of 95%. This underscored that MRD-negativity after surgery and adjuvant endocrine therapy is associated with an exceptionally low risk of distant recurrence.
MRD-positive patients had very poor outcomes with current therapy.

Baseline MRD positivity was observed in roughly 8% of this stage II–III HR+/HER2- population. These patients had 5-year DRFI of 28%, corresponding to a markedly elevated hazard of distant recurrence compared with MRD-negative patients (hazard ratio [HR] ~15). At the end of protocol-directed therapy, MRD-positive patients had a 5-year DRFI of 32%, with hazard ratios exceeding 20 versus MRD-negative patients.
There was strong prognostic value across all postoperative timepoints tested in the analysis.

Signatera ctDNA status at baseline, C6D1 and EOT was consistently and strongly associated with distant recurrence risk, even when accounting for clinical and pathologic features. Across these timepoints, MRD-positive patients had hazard ratios well into the double digits (13.4-21.5) compared with MRD-negative patients, demonstrating much larger risk separation than is typically seen with individual clinicopathologic factors alone.
"ctDNA has emerged as one of the most promising biomarkers in early-stage breast cancer, and the TransPALLAS collaboration gives us a uniquely powerful opportunity to study ctDNA in the adjuvant setting," said Heather Parsons, M.D., MPH, first author, Trans-PALLAS member, and associate professor of the clinical research division and program head of the breast oncology program at Fred Hutch Cancer Center. "We are excited to share these findings with the breast oncology community and advance a better understanding of recurrence risk for patients with HR+/HER2- disease."

"The results from this preplanned analysis of the PALLAS trial support Natera’s vision for individualizing the management of early-stage HR+/HER2- breast cancer," said Minetta Liu, M.D., chief medical officer of oncology and early cancer detection at Natera. "Implementation of longitudinal post-surgical ctDNA testing with Signatera advances us beyond a one‑size‑fits‑all management approach based solely on initial tumor characteristics. Instead, we can start to imagine treatment algorithms where ctDNA-negative patients are spared unnecessary treatment with related toxicity, and ctDNA-positive patients are prioritized for more intensive or novel therapies. It’s a fundamental shift toward truly MRD‑informed care."

About the PALLAS Trial

PALbociclib CoLlaborative Adjuvant Study (PALLAS) (NCT02513394) is a randomized (1:1), prospective, international, multicenter, open-label Phase 3 study comparing the combination of palbociclib in combination with endocrine therapy (ET) versus ET alone for adults with HR+, HER2- Stage II and Stage III EBC, including those at moderate to high risk of recurrence. MRD detection via ctDNA testing was a predefined biomarker analysis to identify patients at highest risk of recurrence. The previously reported trial which did not include MRD analysis, co-sponsored by the ABCSG and the AFT as part of a clinical research collaboration with Pfizer, Breast International Group (BIG), German Breast Group (GBG), National Surgical Adjuvant Breast and Bowel Project (NSABP), and PrECOG, LLC (PrECOG), did not meet its primary endpoint, showing no benefit of palbociclib plus endocrine therapy in the adjuvant setting in patients with histologically confirmed HR+/HER2- invasive EBC. Palbociclib is not approved in EBC.

(Press release, Natera, DEC 10, 2025, View Source [SID1234661362])

On December 10, 2025 Prelude Corporation (PreludeDx), a leader in precision diagnostics for early-stage breast cancer, reported results from the first independent validation of AidaBreast, a novel multi-omic biosignature developed to predict a woman’s 10-year risk of locoregional recurrence (LRR) and her individualized benefit from adjuvant radiation therapy (RT) following breast-conserving surgery.

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The findings will be presented at the San Antonio Breast Cancer Symposium (SABCS) 2025 by Dr. Bruce Mann, Director of Research at Breast Cancer Trials, Head of Breast Surgical Research at Royal Melbourne Hospital, Professor of Surgery at The University of Melbourne, and Principal Investigator of the study, together with Troy Bremer, PhD, Chief Scientific Officer of PreludeDx.

The validation study, conducted at Royal Melbourne Hospital (RMH) in Australia, evaluated more than 400 women with early-stage HR+ / HER2- invasive breast cancer who underwent breast-conserving surgery and endocrine therapy, with or without radiation therapy. The results confirmed and strengthened PreludeDx’s initial validation:

AidaBreast stratifies women into Low Risk and Elevated Risk groups based on underlying tumor biology.
Within the Elevated Risk group, the test identifies which women are likely to experience significant therapeutic benefit from RT, and which show minimal benefit from RT, despite elevated recurrence risk.
Women in the Low Risk group demonstrated very low 10-year recurrence rates whether or not they received radiation therapy.
"This independent blinded validation confirms the prior results, demonstrating that AidaBreast is prognostic for LRR risk and predictive for RT benefit. The results demonstrated that the test identified patients who are good candidates for the omission of RT and patients who would significantly benefit from radiation therapy," said Dr. Bruce Mann, Principal Investigator of the study. "AidaBreast provides information that cannot be determined from clinicopathology alone and offers a major advance in early-stage invasive breast cancer treatment."

AidaBreast: The First and Only Test Providing Both Prognostic and Predictive Insight for Radiation Therapy

AidaBreast uses multi-omic technology by analyzing RNA and protein expression together with spatial biology, providing a more complete assessment of a patient’s tumor biology.

"AidaBreast provides a new level of clarity for women with early-stage invasive breast cancer," said Dan Forche, President and CEO of PreludeDx. "For the first time, patients and physicians have a tool for Stage I and IIa breast cancer that supports shared treatment decisions, helping women make more confident and informed choices on radiation therapy."

AidaBreast: The Next Generation of Insight for Early-Stage Breast Cancer

AidaBreast assessment of RT benefit is the first in a comprehensive approach for early-stage invasive breast cancer. Future plans include evaluation of endocrine therapy and chemotherapy benefit, enabling a unified, integrated decision-support tool.

"This is the first and only commercially available test developed specifically for RT in Stage I and IIa breast cancer", said Dr. Troy Bremer, CSO. "Prior tests were focused on metastatic risk and chemotherapy benefit. AidaBreast incorporates both RNA and functional proteins that drive tumor biology, giving patients and clinicians the first tool for assessing both recurrence risk and predicting radiation therapy benefit."

Extending the Proven Impact of DCISionRT

AidaBreast builds on PreludeDx’s leadership established with DCISionRT, the widely adopted test that transformed radiation therapy decision-making for women diagnosed with ductal carcinoma in situ (DCIS).

"With AidaBreast, we are bringing the same level of precision and biological insight to early-stage invasive breast cancer," added Forche. "Our goal is to ensure women have the clearest possible understanding of their treatment options so they can make the best decision for their health and quality of life."

About DCISionRT

DCISionRT is the only risk assessment test for patients with ductal carcinoma in situ (DCIS) that predicts radiation therapy benefit. Patients with DCIS have cancerous cells lining the milk ducts of the breast, but they have not spread into surrounding breast tissue. In the US, over 60,000 women are newly diagnosed with DCIS each year. DCISionRT, developed by PreludeDx on technology licensed from the University of California San Francisco, and built on research that began with funding from the National Cancer Institute, enables physicians to better understand the biology of DCIS. The test provides a Decision Score that identifies a woman’s risk as low, elevated, or residual risk. Unlike other risk assessment tools, the DCISionRT test combines protein expression from seven biomarkers and four clinicopathologic factors, using a non-linear algorithm to account for multiple interactions between individual factors to better interpret complex biological information. DCISionRT’s intelligent reporting provides a woman’s recurrence risk after breast conserving surgery alone and with the addition of radiation therapy. In turn, this new information may help patients and their physicians to make more informed, personalized treatment decisions.

(Press release, PreludeDx, DEC 10, 2025, View Source [SID1234661361])

On December 10, 2025 Indivumed reported its partnership with the world-renowned Wilmot Cancer Institute at the University of Rochester Medical Center (URMC). Leveraging Indivumed’s proven approach to standardized tissue and clinical data collection for patient-centric cancer R&D, this collaboration aims to accelerate the development of novel cancer therapeutics for patients with high medical need.

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An integral resource for patient-centric cancer R&D

Indivumed’s innovative platform builds on carefully collected and curated surgical tissue samples and comprehensive clinical data to drive patient-centric cancer research and drug development. URMC’s invaluable role includes the collection and processing of high-quality biosamples and clinical patient data, adhering to Indivumed’s rigorous standard operating procedures (SOPs). A key advantage is minimizing ischemia time to under ten minutes, ensuring sample integrity and quality.

Priority of the joint research efforts is the creation of well-characterized, patient-derived tumor models (PDTMs) from the very same samples. These cell models, including classical cell cultures, spheroids, and organoids, combined with data insights subsequently serve to advance and de-risk the process of identification, validation, ligand screening, and development of pharmaceutical molecular cancer targets.

Hartmut "Hucky" Land, PhD, Deputy Director of the Wilmot Cancer Institute, is looking forward to the collaboration: "We have worked with Indivumed successfully in the past and our familiarity with their tissue and multi-omics data approach will provide an excellent foundation. The new project will create greater opportunities to identify new therapeutics and biomarkers, uncover insights on the right target-patient match for clinical decision-making, and thus help advance cancer care."

Focusing on advanced stages of specific entities

The collaboration initially focuses on advanced stages of solid cancers with a high medical need, such as colorectal (CRC), pancreatic (PDAC), lung, and breast cancer, with the potential to expand to other cancer types in the future. Insights gained through this partnership will advance Indivumed’s ongoing research initiatives and asset development, while offering participating clinicians valuable guidance to inform therapeutic decision-making.

"We are thrilled to deepen our collaboration with URMC, significantly enhancing our ability to identify novel cancer therapeutics in a truly patient-centered approach," says Hartmut Juhl, CEO and founder of Indivumed. "We will develop primary tumor models for the testing of novel compounds against targets which have been identified by our unique AI-powered data analytical capabilities to bring novel therapeutics to patients as fast and precisely as possible."

With this agreement, the University of Rochester Medical Center joins the Indivumed Global Clinical Network, which already includes a sizeable number of renowned hospitals and leading oncology institutes in North America, Europe and Asia. The collaboration builds on the success of previous collaborations with joint research efforts between the two parties, including a recent publication on the discovery of an alternative way to classify distinct types of colon cancer.

(Press release, Indivumed Therapeutics, DEC 10, 2025, View Source [SID1234661360])

On December 10, 2025 IceCure Medical Ltd. (NASDAQ: ICCM) ("IceCure", "IceCure Medical" or the "Company"), developer of minimally-invasive cryoablation technology that destroys tumors by freezing as an option to surgical tumor removal, reported that four abstracts featuring data from independent studies conducted by ProSense users were accepted and presented at the Radiological Society of North America’s ("RSNA") Annual Meeting, which took place from November 30 to December 4, 2025 in Chicago, Illinois.

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The RSNA’s Annual Meeting, the world’s largest radiology conference with around 50,000 attendees from 160 countries, is a prestigious global platform for presenting clinical data. The acceptance of four abstracts this year, each showcasing results achieved with IceCure’s technology, represents another significant international recognition of the effectiveness and growing adoption of ProSense by the medical community for the treatment of breast cancer.

"The broad range of independent studies conducted, peer reviewed, published and presented by ProSense users supports the widescale adoption of our cryoablation system and is highly encouraging for women who seek a non-surgical option," said Eyal Shamir, IceCure’s Chief Executive Officer. "At RSNA 2025, radiologists from across the U.S. and the globe gathered to learn about the latest technologies that can lead to better patient outcomes, and we are proud that ProSense was presented to these doctors. We continue to see growing interest in ProSense following the U.S. Food and Drug Administration’s ("FDA") recent marketing approval in low-risk breast cancer."

Independent studies presenting data on ProSense included the following:

1. Abstract Title: Ultrasound-guided Cryoablation for Breast Cancer in Non-Surgical Patients

Key Finding: PCA was successful in 100% of luminal cancers up to 2.5 cm

Researchers (Spain): Laura Abelairas Lopez, MD, Lucia Grana Lopez, MD, Laura Lopez, MD, Ignacio Fernandez Sobrado

Purpose: To present a single-center experience on the use of percutaneous cryoablation ("PCA") for the local control of breast cancer ("BC") in patients who elect not to undergo a surgery or were considered inoperable

Results: 73 women who were considered inoperable were treated under local anesthesia with PCA. 69 of them (median age 87 years, range 48-98 years) had at least one imaging examination performed 6 months after the procedure. Median tumor size was 23 mm, range 6-46 mm. The mean follow-up was 19.8 months (range 6-45 months). 60 patients were luminal BC, 3 were Her2 (+) and 8 were triple negative tumors. All luminal cancers received endocrine therapy. Complete tumoral necrosis was achieved in 56 tumors (81.2%). There was axillary progression in two triple negative BC. Recurrence in a different location was diagnosed in two patients. PCA was successful in 100% of luminal cancers up to 2.5 cm. No major complications were seen and the procedure was well tolerated.

Conclusions: Percutaneous cryoablation is a minimally invasive procedure, without significant complications. It could be a safe alternative to surgery for the management of early-stage breast cancer.

2. Abstract: Non-Surgical Treatment of Breast Cancer: A Comparison of Outcomes Between Cryoablation with Hormonal Therapy Versus Cryoablation Alone and Hormonal Therapy Alone in Patients Not Eligible for Surgery

Key Finding: Statistically significant difference between the Cryoablation-with-HT and the HT-only groups, expressing the added value of Cryoablation

Researchers (Italy): Federica Di Naro, MD, Sofia Elisabetta Baldi Giorgi, Francesca Pugliese, MD, Sofia Vidali, Tommaso Amadori, MD, Diego De Benedetto, Jacopo Nori Cucchiari

Purpose: To evaluate the most effective non-surgical treatment for breast cancer in surgery-ineligible patients, comparing ultrasound-guided Cryoablation combined with hormonal therapy (HT) versus Cryoablation alone and hormonal therapy alone

Results: 111 patients (mean age 81.2 years, ±11.3) not-suitable for surgery due to comorbidities and/or advanced age were enrolled, with a total of 125 biopsy-confirmed malignant breast lesions. Tumor size reduction was significantly different between the groups (P=0.0005), with greatest reduction in the Cryoablation-with-HT group (83.3%, mean reduction of 13.6 mm), followed by Cryoablation-only (61.7%, mean reduction of 8.2 mm), and HT-only (42.1%, mean reduction of 7.4 mm). Tumors with complete remission (CR, RECIST 1.1) were similar between the Cryoablation-with-HT and Cryoablation-only groups (74.4% and 78.3%, respectively), followed by the HT-only (36.1%). Pairwise comparisons revealed a significant difference between the Cryoablation-with-HT and the HT-only groups for Contrast-Enhanced Mammography ("CEM")-enhancement, size reduction (%), and CR, expressing the added value of Cryoablation (P=0.0041, P<0.0001 and P<0.0001, respectively).

Conclusions: Cryoablation with hormonal-therapy significantly reduces tumor size and residual disease more effectively than therapy alone, making it a promising option for patients not-eligible for surgery.

3. Abstract Title: Correlation of Lesion Conspicuity in Contrast-Enhanced Mammography (CEM) with Tru-Cut Scar Biopsy Results in the Assessment of Ultrasound-Guided Cryoablation Outcome

Key Finding: Significant association between biopsy and lesion conspicuity on CEM

Researchers (Spain): Federica Di Naro, MD, Francesca Pugliese, MD, Sofia Elisabetta Baldi Giorgi, Giuliano Migliaro, MD, Giulia Bicchierai, Chiara Bellini, MD, Jacopo Nori Cucchiari

Purpose: To evaluate the role of lesion conspicuity at 12-month CEM follow-up as a predictor of cryoablation outcome

Results: 79 patients (mean age 85.7 years old, ±6.0) with biopsy-proven malignant breast lesions ≤35 mm, underwent ultrasound-guided cryoablation. Among the 79 patients, 48 (60.8%) underwent both CEM and Biopsy at 12 months. Among them, 35 (61.4%) lesions showed no enhancement. Among the 22 (38.6%) lesions showing enhancement, 6 had low LC, 11 moderate LC, and 5 high LC. A significant fair agreement (Cohen’s Kappa coefficient = 0.32 [95% CI: 0.11-0.52]) between CEM and biopsy was shown. Fisher’s exact test P-value was 0.0003 reflecting a significant association between biopsy and conspicuity. Lesions with absent or low LC correlated with negative histology (B2), while lesions with residual malignant histology (B5) were associated with moderate-high LC. In assessing cryoablation efficacy, CEM demonstrated negative predictive value (NPV) of 100%, Sensitivity of 100%, Specificity of 68.6% and positive predictive value (PPV) of 27.3%.

Conclusions: Lower lesion conspicuity on CEM indicates higher cryoablation success, useful for follow-up.

4. Abstract Title: Imaging Findings After Cryoablation of Breast Cancer: Tips and Tricks to Know That the Procedure was Successful Without Biopsy

Researchers (Spain): Laura Abelairas Lopez, MD, Lucia Grana Lopez, MD, Laura Lopez, MD, Ignacio Fernandez Sobrado

Teaching Points: Described the findings on mammography, ultrasound, and CEM after PCA of breast BC, as well as the signs of residual tumor or recurrence.

About ProSense

The ProSense Cryoablation System is the first and only medical device to receive FDA marketing authorization for the local treatment of low-risk breast cancer with adjuvant endocrine therapy for women aged 70 and above, including patients who are not suitable for surgical alternatives for breast cancer treatment. A full list of benefits and risks can be found on the Company’s website.

ProSense is a minimally invasive cryosurgical tool that provides the option to destroy tumors by freezing them. The system uniquely harnesses the power of liquid nitrogen to create large lethal zones for maximum efficacy in tumor destruction in benign and cancerous lesions, including in the breast, kidney, lung, and liver.

ProSense enhances patient and provider value by accelerating recovery, reducing pain, surgical risks, and complications. With its easy, transportable design and liquid nitrogen utilization, ProSense opens the door to fast and convenient office-based procedures for breast tumors.

(Press release, IceCure Medical, DEC 10, 2025, View Source [SID1234661359])

On December 10, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, reported the submission of an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for IDE574, a potential first-in-class KAT6/7 dual inhibitor with high selectivity over related KAT5/8 enzymes. The company is targeting to begin a Phase 1 dose escalation trial of monotherapy IDE574 in the first quarter of 2026.

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"IDE574 is a promising potential first-in-class molecule that potently inhibits two tumor-promoting epigenetic modulators, KAT6 and KAT7, while sparing other structurally similar KAT family members. Preclinical studies demonstrate KAT6 and KAT7 collaboratively control lineage-specific tumorigenic transcription factor activity essential for tumor cell proliferation and survival. Dual KAT6/7 inhibition by IDE574 disrupts tumor lineage identity and delivers robust anti-tumor activity in patient-derived lung and breast cancer xenograft models dependent upon lineage-specific transcription factor activity," said Michael White, Ph.D., Chief Scientific Officer of IDEAYA Biosciences.

IDE574 is an equipotent, highly selective, small molecule dual inhibitor of the lysine acetyltransferase (KAT) 6 and 7, both of which have been shown to support cancer cell survival. IND-enabling studies support the potential clinical evaluation of IDE574 monotherapy in patients with hormone receptor-positive breast cancer, lung adenocarcinoma as well as additional opportunities associated with lineage addiction. IDEAYA is targeting to share data from its preclinical work with IDE574 at a medical conference in the first half of 2026.

(Press release, Ideaya Biosciences, DEC 10, 2025, View Source [SID1234661358])