Patient deaths prompt partial hold for Daiichi-Merck’s global phase 3 ADC program

On December 18, 2025 Daiichi Sankyo and Merck & Co. reported that phase 3 program for their investigational antibody-drug conjugate has been hit with a hold after an unexpected number of deaths were reported in the global trial.

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"Due to a higher than anticipated incidence of grade 5 interstitial lung disease (ILD) events identified in the IDeate-Lung02 phase 3 trial, Daiichi Sankyo initiated a voluntary pause in recruitment and enrollment," a spokesperson for the partners told Fierce Biotech. The companies did not answer questions regarding how many deaths have occurred.

"Following the initial pause, the FDA has placed the trial on a partial clinical hold," the spokesperson explained.

The unexpected deaths come as the pharma partners said they were aiming for an accelerated approval of the investigational B7-H3-directed ADC—known as ifinatamab deruxtecan or I-DXd—for pretreated small cell lung cancer (SCLC) based on a phase 2 readout. In 2023, Merck paid out $5.5 billion in upfront and near-term payments to gain access to a clutch of Daiichi’s ADCs.

Under the hold, Daiichi will work with the FDA and an independent data monitoring committee to review safety data and "determine any necessary further actions," the spokesperson told Fierce.

"Of note, it does not impact other studies in the I-DXd clinical development program," the spokesperson added.

Patients currently enrolled in IDeate-Lung02 will be able to continue treatment, but no new participants will be recruited during this time, according to the spokesperson.

"We are evaluating the potential impact of the partial clinical hold on study data readout timing, currently projected for fiscal year 2027," the spokesperson said.

The deaths and consequential hold have not been announced publicly by either Merck or Daiichi, but instead were first reported by oncology-focused publication ApexOnco. The temporary halts began in several European countries—such as France, Germany and Italy—at the end of September, according to the European clinical trial registry.

(Press release, FierceBiotech, DEC 18, 2025, https://www.fiercebiotech.com/biotech/patient-deaths-prompt-partial-hold-daiichi-mercks-global-phase-3-adc-program [SID1234661552])

Abdera Therapeutics to Present at the 44th Annual J.P. Morgan Healthcare Conference on Tuesday, January 13

On December 18, 2025 Abdera Therapeutics Inc., a clinical-stage biopharmaceutical company leveraging its advanced antibody engineering ROVEr platform to design and develop tunable precision radiopharmaceuticals for cancer, reported that Lori Lyons-Williams, president and chief executive officer, will present at the 44th Annual J.P. Morgan Healthcare Conference on Tuesday, January 13, 2026 at 10:00 a.m. PT.

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Ms. Lyons will provide an overview of the company and its pipeline of first-in-class radiotherapeutics, including ABD-147 targeting delta-like ligand 3 (DLL3) that is currently being evaluated in a Phase 1 clinical trial for the treatment of small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), and ABD-320, targeting 5T4 with pan-cancer potential, which is on-track to enter clinical development in 2026.

(Press release, Abdera Therapeutics, DEC 18, 2025, View Source [SID1234661551])

DATROWAY® Type II Variation Application Validated in the EU as First-Line Treatment for Patients with Metastatic Triple Negative Breast Cancer Who are Not Candidates for Immunotherapy

On December 18, 2025 Daichii Sankyo reported that European Medicines Agency (EMA) has validated the Type II Variation marketing authorization application for DATROWAY (datopotamab deruxtecan) as monotherapy for the first-line treatment of adult patients with unresectable or metastatic triple negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.

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DATROWAY is a specifically engineered TROP2 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 validation confirms the completion of the application and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. The application is based on data from the TROPION-Breast02 phase 3 trial presented in a late-breaking proffered paper session at the 2025 European Society for Medical Oncology (#ESMO25) Congress. In the trial, DATROWAY demonstrated statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) compared to investigator’s choice of chemotherapy as first-line treatment for patients with metastatic TNBC for whom immunotherapy was not an option.

"DATROWAY has shown the potential to replace traditional chemotherapy and improve survival for patients with metastatic triple negative breast cancer, the most aggressive type of breast cancer with one of the worst prognoses," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "This EMA validation represents the potential for a second indication for DATROWAY in breast cancer and another step forward in the approval process in Europe."

"Approximately seven of every ten patients with metastatic triple negative breast cancer are unable to receive immunotherapy due to the biology of their tumors or other factors. Chemotherapy remains the first-line standard of care for these patients," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. "With this validation of our application for DATROWAY, based on the pivotal TROPION-Breast02 results, we have taken a meaningful step towards bringing these patients in Europe an alternative to traditional chemotherapy for the first time."

Additional regulatory submissions for DATROWAY in this indication are underway globally.

About TROPION-Breast02
TROPION-Breast02 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of DATROWAY versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumors did not express PD-L1 as well as patients with PD-L1 expressing tumors who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrollment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as stable brain metastases.

The dual primary endpoints of TROPION-Breast02 are PFS as assessed by blinded independent central review and OS. Secondary endpoints include PFS as assessed by investigator, objective response rate, duration of response, disease control rate, pharmacokinetics and safety.

TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

About Triple Negative Breast Cancer
TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 345,000 diagnoses globally each year.1,2 In Europe, TNBC represents 24% of all breast cancer cases, with an estimated 83,000 diagnoses each year.3 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women.4,5,6 Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses, with median OS of just 12 to 18 months and only about 14% of patients living five years following diagnosis.4,7,8

While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three.4 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat.4 For patients with metastatic disease with PD-L1 expressing tumors, the addition of immunotherapy to chemotherapy has improved outcomes in the first-line setting.9,10 However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy remains the first-line standard of care.11,12

TROP2 is a protein broadly expressed in several solid tumors, including TNBC.13 TROP2 is associated with increased tumor progression and poor survival in patients with breast cancer.14, 15

About DATROWAY
DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

DATROWAY (6 mg/kg) is approved in more than 35 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial.

DATROWAY (6 mg/kg) is approved in Russia and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy, based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the DATROWAY Clinical Development Program
A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including NSCLC, TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer, five phase 3 trials in breast cancer and one phase 3 trial in urothelial cancer evaluating DATROWAY as a monotherapy and in combination with other cancer treatments in various settings.

(Press release, Daiichi Sankyo, DEC 18, 2025, View Source [SID1234661550])

Natera Announces Publication of Signatera™ Analysis from Randomized, Phase III CALGB (Alliance)/SWOG 80702 Study in Colorectal Cancer

On December 18, 2025 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, reported the publication of findings from the randomized, phase III CALGB (Alliance)/SWOG 80702 study in JAMA Oncology. This publication builds on the initial presentation of results at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Gastrointestinal Cancers Symposium (ASCO GI) earlier this year.

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CALGB (Alliance)/SWOG 80702 assessed the predictive value of postoperative personalized circulating tumor DNA (ctDNA) in patients with stage III colorectal cancer (CRC). The pre-specified post-hoc analysis included 940 patients with available post-surgical plasma samples, who were randomized to receive FOLFOX +/- celecoxib, a non-steroidal anti-inflammatory drug (NSAID). Key findings included:

Adding celecoxib to conventional chemotherapy in Signatera-positive patients, after surgery reduced the risk of cancer recurrence and death by ~40%. Celecoxib improved disease-free survival (DFS) (adjusted HR=0.61, 95% CI 0.42-0.89; 3-year 41.0% vs. 22.6%) and overall survival (OS) (adjusted HR=0.62, 95% CI 0.40-0.96; 5-year: 61.6% vs. 39.9%) compared to placebo in Signatera-positive patients.
Celecoxib benefit in Signatera-positive patients was independent of demographic, pathologic or molecular factors, including PIK3CA status, further defining a patient population who may benefit from the addition to adjuvant treatment. Celecoxib improved DFS of Signatera-positive patients for both PIK3CA wild-type (adjusted HR=0.64, 95% CI 0.42-0.98) and PIK3CA altered (adjusted HR=0.19, 95% CI 0.06-0.58) tumors. No benefit was observed in Signatera-negative patients (PIK3CA wild-type adjusted HR=0.80, 95% CI 0.55-1.18; PIK3CA altered HR=0.85, 95% CI 0.33-2.24).
New analysis showed statistical significance in the interaction between MRD status and treatment randomization. In 66% of patients with plasma and DNA samples that would pass minimum QC criteria for Signatera analysis in the CLIA lab, analysis showed an even stronger benefit for adjuvant celecoxib than in the overall cohort (adjusted HR=0.49); and it showed significance in the statistical interaction test comparing the effect of celecoxib vs. placebo between patients who were Signatera positive vs. negative. In Natera’s standard lab practice, 99% of plasma and DNA samples meet QC criteria.
"For patients with detectable ctDNA after surgery, adding celecoxib to standard chemotherapy improved both DFS and OS," said Jonathan Nowak, M.D., Ph.D., Brigham and Women’s Hospital, and corresponding author of the publication. "In addition to highlighting Signatera’s predictive abilities in this setting, the publication also underscores its value as a prognostic marker for disease recurrence and survival."

"This publication marks another important milestone in colorectal cancer research, highlighting Signatera as a critical tool in disease management," said Adham Jurdi, M.D., senior medical director of GI oncology at Natera. "It further demonstrates Signatera’s predictive utility in identifying, with great precision, patients with MRD who will likely benefit from celecoxib in addition to chemotherapy, regardless of their PIK3CA status."

(Press release, Natera, DEC 18, 2025, View Source [SID1234661549])

Incyte to Present at Upcoming Investor Conference

On December 18, 2025 Incyte (Nasdaq:INCY) reported that it will present at the 44th Annual J. P. Morgan Healthcare Conference on Monday, January 12, 2026 at 8:15 am (PST).

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The presentation will be webcast live and can be accessed at Investor.Incyte.com and will be available for replay for 30 days.

(Press release, Incyte, DEC 18, 2025, View Source [SID1234661548])