On October 18, 2025 Alphamab Oncology (Stock Code: 9966.HK) reported that the first interim analysis results of a phase III clinical trial of anbenitamab injection (KN026), independently developed by the Company and co-developed with JMT-Bio Technology Co., Ltd., a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. (stock code: 1093.HK), in combination with chemotherapy as second-line or above treatment of HER2-positive gastric cancer (GC) (including gastroesophageal junction cancer (GEJ)) (Study ID: KN026-001, also known as KC-WISE), have been presented at the 2025 European Society for Medical Oncology Congress (ESMO Congress 2025) Late-Breaking Abstract (LBA) Oral Presentation Session.

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LBA Oral Presentation Session is a highly anticipated global highlight of the ESMO (Free ESMO Whitepaper) Congress. The research presented in this category is both highly topical and of significant clinical value. Their findings often herald potential impacts on current clinical practice and can even guide the future direction of entire therapeutic fields.

Title：KN026 in combination with chemotherapy for previously treated HER2-positive gastric or gastroesophageal carcinomas (GC/GEJC): Interim analysis of KC-WISE

Number: LBA 78

Speaker: Jianming Xu, Chinese PLA General Hospital

Date：Friday, 17 October 2025

METHODS

Enrolled patients in study KN026-001 (KC-WISE) with HER2-positive GC/GEJ who had disease progression after trastuzumab-based therapy were randomized to receive either anbenitamab (KN026) in combination with chemotherapy (the "Anbenitamab Group") or chemotherapy with placebo (the "Control Group"). The patients were stratified based on (i) type of chemotherapy, (ii) HER2 expression level, and (iii) number of prior lines of treatments.

RESULTS

At baseline, patient characteristics were generally well balanced between the two groups. The median age was approximately 64 in the Anbenitamab Group and 61 in the Control Group. In both groups, over 80% of patients had an ECOG PS of 1, and nearly all patients were diagnosed with stage IVB disease at enrollment. All patients had previously received chemotherapy, most commonly taxanes (over 70%), with the remainder receiving irinotecan-based regimens.

As of April 3, 2025, the median follow-up duration was 9.7 months (95% CI, 7.2 to 11.9 months) in the Anbenitamab Group and 9.8 months (95% CI, 7.4 to 12.9 months) in the Control Group.

Efficacy as assessed by the Independent Review Committee (IRC):

● The median treatment-related adverse event (PFS) for the Anbenitamab Group was 7.1 months, compared with 2.7 months in the Control Group. The hazard ratio (HR) is 0.25 (P value is 5.44 × 10⁻¹²), corresponding to a 75% reduction in the risk of disease progression or death.

● The median overall survival (OS) for the Anbenitamab Group was 19.6 months (not mature), compared with 11.5 months in the Control Group. The HR is 0.29, representing a 71% reduction in the risk of death, and P value is 1.56 × 10⁻6, which is well below the prespecified extremely stringent alpha threshold of 0.00001.

● The objective response rate (ORR) was 55.8% in the Anbenitamab Group versus 10.8% in the Control Group, while the disease control rate (DCR) was 80.0% and 41.9%, respectively. The median duration of response (DoR) was 8.2 months and 2.9 months, respectively.

Safety:

● The median treatment duration was 6.5 cycles in the Anbenitamab Group and 3.0 cycles in the Control Group.

● The incidence of Grade 3 treatment-emergent adverse events (TEAEs) or above was 60.6% in the Anbenitamab Group and 51.6% in the Control Group, while the incidence of serious adverse events (SAEs) was 31.9% and 33.3%, respectively.

● The most frequently observed Grade 3 treatment-related adverse events (TRAEs) or above in the Anbenitamab Group included neutropenia (29.8%), leukopenia (21.3%), anemia (18.1%), diarrhea (8.5%) and asthenia (8.5%), while the most frequently observed Grade 3 TRAEs or above in the Control Group included leukopenia (24.7%), neutropenia (21.5%), anemia (10.8%), diarrhea (7.5%) and thrombocytopenia (5.4%). The incidence of cardiotoxicity in both groups were both 3.2%, indicating fewer cardiac concerns.

CONCLUSIONS

The interim analysis demonstrated that anbenitamab achieved superior efficacy in second-line or third-line HER2-positive gastric cancer patients who had been previously treated with trastuzumab. The study met both its primary endpoints of PFS and OS with statistically significant and clinically meaningful improvements, indicating its potential to change clinical practice guidelines for the treatment of second-line or above gastric cancer. Compared with the recently published DESTINY-Gastric04 results of DS-8201 in second-line gastric cancer, anbenitamab demonstrates potential advantages in both efficacy and safety.

Prompted by these encouraging results of anbenitamab, we are preparing to expand clinical development into first-line and perioperative gastric cancer through new registrational trials, aiming to extend benefits to more patients. Meanwhile, JSKN003, an ADC built upon KN026, has demonstrated high-security profile and distinctive advantages. With multiple registrational studies currently advancing as planned, we anticipate even more outstanding performance from JSKN003 in the future.

About Anbenitamab (KN026)

Anbenitamab (KN026) is an anti-HER2 bispecific antibody independently developed by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology called CRIB (Charge Repulsion Induced Bispecific). KN026 can simultaneously bind two non-overlapping epitopes of HER2, resulting in HER2 signal blockade.

Results from multiple clinical studies showed that KN026 has promising efficacy for the treatment of HER2-positive solid tumors, both in the first-line and in patients previously treated with trastuzumab. Currently, several pivotal trials of KN026 for second-line or above HER2-positive GC/gastroesophageal junction cancer (GEJ), first-line HER2-positive BC, neoadjuvant treatment of HER2-positive BC are being conducted. KN026 for the treatment of patients with HER2-positive GC who have failed first-line standard treatment was granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA). KN026 for the treatment of HER2-positive or low expressing GC was granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA). In September 2025, the first New Drug Application (NDA) for anbenitamab injection has been accepted by the NMPA for use in combination with chemotherapy in patients with HER2-positive locally advanced, recurrent, or metastatic GC/GEJ who have failed at least one prior systemic therapy (which must include trastuzumab in combination with chemotherapy).

In August 2021, the Company entered an agreement with JMT-Bio Technology Co., Ltd. ("JMT-Bio"), a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. ("CSPC") (stock code: 1093.HK), for the development and commercialization of KN026 in Mainland China. JMT-Bio was granted exclusive license rights of KN026 for the development and commercialization in the indications of BC an GC/GEJ in Mainland China (excluding Hong Kong, Macau and Taiwan).

(Press release, Alphamab, OCT 18, 2025, View Source [SID1234656997])

On October 18, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive results from the Phase III evERA Breast Cancer study. Data showed giredestrant in combination with everolimus significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 44% and 62% in the intention-to-treat (ITT) and ESR1-mutated populations, respectively, compared with standard-of-care endocrine therapy plus everolimus. The evERA study is evaluating the investigational giredestrant combination in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. This is the first positive head-to-head Phase III trial investigating a selective estrogen receptor degrader-containing regimen versus a standard-of-care combination. The results are being presented in an oral session at the European Society for Medical Oncology Congress 2025. Data will be shared with health authorities, with the aim of bringing this potential treatment option to people as soon as possible.

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"A particularly high unmet need remains for people who become resistant to endocrine therapies and CDK inhibitors. These study results support the potential for the giredestrant combination to become a new standard-of-care for all patients in this setting," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development.

"Resistance to standard-of-care therapies is common in the post-CDK inhibitor setting, and the results from evERA validate using a combination to address this challenge," said Erica L. Mayer, M.D., Medical Oncologist at Dana-Farber Cancer Institute. "The clinically meaningful benefit observed with the giredestrant and everolimus all-oral combination is impressive and speaks to its potential to improve outcomes for patients in need of new treatment options."

The giredestrant combination demonstrated a statistically significant and clinically meaningful improvement in PFS compared with standard-of-care endocrine therapy plus everolimus. In the ITT population, the median PFS was 8.77 months compared with 5.49 months in the giredestrant and comparator arm, respectively (stratified hazard ratio [HR]=0.56; 95% CI: 0.44-0.71, p-value= <0.0001). In the ESR1-mutated population, the median PFS was 9.99 months compared with 5.45 months in the giredestrant and comparator arm, respectively (HR=0.38; 95% CI: 0.27-0.54, p-value= <0.0001). The PFS benefit was consistent across pre-specified subgroups in both populations. Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed in the ITT (HR=0.69, 95% CI: 0.47-1.00, p-value=0.0473) and ESR1-mutated populations (HR=0.62, 95% CI: 0.38-1.02, p-value=0.0566). Follow-up for OS will continue to next analysis. Giredestrant in combination with everolimus also demonstrated improvements in key secondary endpoints (objective response rate and duration of response) compared with the comparator arm across both patient populations.

Adverse events for the giredestrant-based combination were manageable and consistent with the known safety profiles of the individual medicines. No new safety signals were observed, including no photopsia.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes. All-oral combination therapies, such as giredestrant plus everolimus, could address this by targeting two different signaling pathways while helping to minimize the impact of treatment on people’s lives without the need for injections.

Our extensive giredestrant clinical development program spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.

About the evERA Breast Cancer study

evERA Breast Cancer [NCT05306340] is a Phase III, randomized, open-label, multicenter study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.

The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomization to the time when the disease progresses or a patient dies from any cause. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.

About estrogen receptor (ER)-positive breast cancer

Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year. Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. A defining feature of ER-positive breast cancer is that its tumor cells have receptors that attach to estrogen, which can contribute to tumor growth.

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity. Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy. There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

About giredestrant

Giredestrant is an investigational oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist.

Giredestrant is designed to block estrogen from binding to the estrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.

Giredestrant has an extensive clinical development program and is being investigated in five company-sponsored Phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)
Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)
Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)
Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)
Giredestrant plus dual HER2 blockade versus dual HER2 blockade in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)

(Press release, Genentech, OCT 18, 2025, View Source [SID1234656757])

On October 17, 2025 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, reported new data from its botensilimab (BOT), a multifunctional, Fc-enhanced CTLA-4 antibody and balstilimab (BAL), a PD-1 inhibitor, combination demonstrating durable survival across multiple cancer types in late-stage patients who have limited treatment options. The results, featured in an oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 in Berlin, Germany presented by Dr. Michael Gordon of HonorHealth Research Institute, include emerging two-year survival plateaus indicating a strong clinical signal that BOT/BAL’s benefit may be agnostic to tumor type.

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"With longer follow up, we’re finding that approximately 40% of patients with very limited survival expectation are alive at two years," said Michael S. Gordon, MD, HonorHealth Research Institute. "These results are in patients with cancers that historically have been resistant to earlier immunotherapy approaches or have progressed following prior immunotherapy treatment, and they support advancing randomized trials like the phase 3 BATTMAN trial to create an immunotherapy option for patients who have historically had none."

Highlights from the Oral Presentation (Abstract #1517MO):

New data from expansion cohorts of 411 patients (339 evaluable for efficacy) enrolled in the Phase 1b C-800-01 study evaluating BOT/BAL in patients with advanced, refractory disease across more than 5 cancer types.

61% of patients enrolled received three or more prior lines of therapy
Objective response rates (ORR): 17% across both BOT 1 mg/kg and 2 mg/kg doses
Signals of benefit across tumor types, including those historically unresponsive to immunotherapy, had prior treatment with checkpoint inhibitors, and/or with active liver metastases.
2-year median overall survival (OS): 39%
Median OS (mOS): 17.2 months
Combination was well tolerated with most immune‑related side effects were reversible and gastrointestinal in nature; no treatment‑related deaths occurred
Immune activation correlated with improved survival
These findings build on previously reported 2-year overall survival of 42% and median OS of 20.9 months with BOT/BAL in refractory MSS mCRC with non-liver metastasesi and complement emerging data in the neoadjuvant setting, where BOT/BAL has also shown activity across multiple tumor typesii, further underscoring the platform potential of Agenus’ next-generation Fc-enhanced CTLA-4.

In a further validation of its clinical impact, the French National Authority for Health (HAS) recently authorized BOT in combination with BAL under France’s Compassionate Access (AAC) early access program. This marks the first government-funded access pathway in France, for patients with refractory microsatellite‑stable (MSS) metastatic colorectal cancer (mCRC) who have exhausted all available treatment options.

"BOT/BAL’s immune activation profile is truly differentiated," said Steven J. O’Day, MD, Chief Medical Officer, Agenus. "We are seeing consistent signals that this combination can convert ‘cold,’ IO‑resistant tumors into responsive ones, not only in late-line settings but potentially in earlier lines where immunotherapy may deliver even greater benefit."

Broader Presence at ESMO (Free ESMO Whitepaper) 2025

In addition to the pan-tumor dataset, three additional posters will be presented highlighting clinical activity across hard-to-treat cancers:

Cervical cancer: Results from the global Phase 2 RaPiDs trial (Abstract #2952)
MSS mCRC: A Phase 1 trial of BOT/BAL + regorafenib (Abstract #6197)
Non-melanoma skin cancer: Data from the AGENONMELA study (Abstract #7273)
These presentations further support the breadth and versatility of Agenus’ immunotherapy pipeline across diverse cancer types and clinical settings.

(Press release, Agenus, OCT 17, 2025, View Source [SID1234656742])

On October 17, 2025 Parabilis Medicines, a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported at the ESMO (Free ESMO Whitepaper) Congress 2025 the first-ever clinical data showing that its investigational FOG-001 therapy has successfully drugged β-catenin:TCF – a key cancer-driving node in the Wnt/β-catenin pathway, until now considered "undruggable."

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In the ongoing Phase 1/2 trial of FOG-001 in patients with a range of Wnt/β-catenin-driven tumors, as of mid-August 2025, 12 patients with desmoid tumors had been dosed across three dose levels. Of the 10 patients who had at least one post-baseline scan, tumor reductions were observed at all dose levels with a 100% disease-control rate (DCR). Of the five patients with more than one post-baseline scan, an objective response rate (ORR) of 80% (4/5) was observed, per RECIST 1.1. Responses were seen in both gamma secretase-naive and –treated patients, and FOG-001 demonstrated clinically meaningful anti-tumor activity alongside acceptable safety and tolerability profiles.

FOG-001 achieves its effect by blocking the interaction between β-catenin and the T-cell factor (TCF) family of transcription factors, the key driver of tumorigenesis in Wnt pathway-activated cancer cells. The data support further development of FOG-001 in patients with desmoid tumors, and suggest that FOG-001, unlike other available therapies for this disease, directly addresses the underlying mechanism of disease through inhibition of β-catenin.

"For decades, scientists had said that the Wnt/β-catenin:TCF interaction couldn’t be drugged, but our data prove otherwise," said Mathai Mammen, M.D., Ph.D., Chairman, CEO and President of Parabilis Medicines. "FOG-001 shows what bold science can achieve — taking on one of cancer’s most important drivers and opening the door to an entirely new class of therapies. This milestone validates the power of Parabilis’s distinctive Helicon peptides and marks an important step forward in our mission to create extraordinary medicines for patients."

The Wnt/β-catenin pathway was first identified over 30 years ago as a fundamental driver of cancer and is implicated in millions of cases each year, across both common cancers — including gastrointestinal cancers like colorectal, hepatocellular, and gastric cancers — as well as many rare cancers such as desmoid tumors and adamantinomatous craniopharyngioma (ACP). Attempts to target the β-catenin:TCF interaction, the key downstream node within the Wnt pathway, have repeatedly failed until now with FOG-001.

Parabilis’s Helicon platform has overcome limitations of traditional small molecule therapeutics by designing stabilized α-helical peptides that gently penetrate cells and bind tightly to proteins with relatively flat binding surfaces. With FOG-001, Parabilis has achieved what decades of cancer research could not: directly drugging the "undruggable" β-catenin:TCF interaction.

Beyond ESMO (Free ESMO Whitepaper), additional clinical data on FOG-001 across a range of Wnt/β-catenin-driven tumors will be presented at several additional upcoming scientific meetings, including the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference on Molecular Targets (October 22-26, Boston, MA), the Connective Tissue Oncology Society (CTOS) 2025 Annual Meeting (November 12-15, Boca Raton, FL), and the Society for Neuro-Oncology (SNO) 2025 Annual Meeting (November 19-23, Honolulu, HI). The company will also share new preclinical data on its allosteric active androgen receptor (ARON) and ERG degrader discovery programs for the treatment of prostate cancer at AACR (Free AACR Whitepaper)-NCI-EORTC and the Prostate Cancer Foundation (PCF) Scientific Retreat (October 23-25, Carlsbad, CA).

Details of the presentations are as follows:

ESMO mini oral information:

Presentation Title: "A Phase 1/2 trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor: Safety and preliminary antitumor activity in patients with desmoid tumors"
Date and Time: Friday, October 17, 2025, 4:00 – 5:30 p.m. CEST
Session: Mini oral session: Sarcoma
Location: Essen Auditorium, Hall 7.2A

AACR-NCI-EORTC oral and poster information:

Title: "A Phase 1/2 trial of FOG-001, a first-in-class direct β-catenin inhibitor, preliminary safety and efficacy in patients with solid tumors bearing Wnt pathway-activating mutations (WPAM+)"
Oral Presentation
Date and Time: Friday, October 24, 2025, 10:00 – 11:40 a.m. EDT
Session: Plenary Session 4: Clinical Trials Plenary Session
Location: Level 3, Ballroom AB
Poster Presentation
Date and Time: Friday, October 24, 2025, 12:30 – 4:00 p.m. EDT
Session: Poster Session B
Location: Level 2, Exhibit Hall D

Poster Title: "Distinct aspects of β-catenin biology drive multiple biologically rational FOG-001 combinations for MSS colorectal cancer"
Date and Time: Saturday, October 25, 2025, 12:30 – 4:00 p.m. EDT
Session: Poster Session C
Location: Level 2, Exhibit Hall D

Poster Title: "Degradation of the ETS transcription factor ERG by stabilized helical peptide (Helicon) degraders enable pharmacological validation in ERG-fusion prostate cancer models"
Date and Time: Friday, October 24, 2025, 12:30 – 4:00 p.m. EDT
Session: Poster Session B
Location: Level 2, Exhibit Hall D

Poster Title: "Discovery of Helicon peptides for the selective degradation of the agonist-bound conformation of androgen receptor (ARON) in prostate cancer"
Date and Time: Friday, October 24, 2025, 12:30 – 4:00 p.m. EDT
Session: Poster Session B
Location: Level 2, Exhibit Hall D

PCF presentation and poster information:

Poster Title: "Discovery of Helicon peptides for the selective degradation of the agonist-bound conformation of androgen receptor (ARON) in prostate cancer"
Date and Time: Thursday, October 23, 2025, 7:30 – 10:30 PM PDT
Location: Costa De La Luna Ballroom

Presentation Title: "Discovery and Optimization of ERG Bifunctional, Stapled Peptide Degraders using Generative AI–Driven Multi-Property Modeling"
Date and Time: Saturday, October 25, 2025, 12:45 – 1:00 PM PDT
Location: Costa Del Sol Ballroom

CTOS poster information:

Poster Title: "A Phase 1/2 trial of FOG-001, a first-in-class direct β-catenin inhibitor: Safety and preliminary antitumor activity in patients with desmoid tumors (DT)"
Date and Time: Thursday, November 13, 2025, 5:30 – 6:30 p.m. EST
Session: Poster Reception: Soft Tissue Tumors

SNO mini oral information:

Presentation Title: "A Phase 1/2 trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor: Safety and preliminary antitumor activity in adamantinomatous craniopharyngioma (ACP) patients"
Abstract Number: CTNI-10
Date and Time: Friday, November 21, 2025, 11:30 – 12:30 p.m. HST
Session: Rapid Orals
Location: Hawaii Convention Center, Kamehameha Exhibit Hall II & III

About the Phase 1/2 trial of FOG-001
FOG-001 is being evaluated in a first-in-human Phase 1/2 multicenter, open-label study (NCT05919264) assessing its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity. The trial includes dose-escalation and dose-expansion phases and is testing FOG-001 both as a monotherapy and in combination with other anticancer agents in patients with advanced or metastatic solid tumors likely or known to harbor a Wnt pathway–activating mutation (WPAM).

About FOG-001
FOG-001 is an investigational first-in-class competitive inhibitor of β-catenin interactions with the T-cell factor (TCF) family of transcription factors and is currently in clinical development. By directly targeting the β-catenin:TCF protein-protein interaction, FOG-001 is intended to block the Wnt signaling pathway irrespective of the various APC and β-catenin mutations that typically drive disease.

FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the key downstream node, disrupting the interaction between β-catenin and the TCF transcription factors, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis.

FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.

(Press release, Parabilis Medicines, OCT 17, 2025, View Source [SID1234656758])

On October 17, 2025 Daiichi Sankyo reported initial results from one sub-study of the TROPION-PanTumor03 phase 2 trial showed that DATROWAY (datopotamab deruxtecan) plus rilvegostomig showed promising tumor responses and disease control as first-line and second-line combination therapy in patients with locally advanced or metastatic urothelial cancer. These results were presented today as a mini oral session (3072MO) at the 2025 European Society for Medical Oncology (#ESMO25) Congress.

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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). Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody.

In a sub-study of patients with locally advanced or metastatic urothelial cancer, DATROWAY plus rilvegostomig was evaluated in both the first-line and second-line treatment settings. As first-line treatment for patients not eligible for cisplatin (n=22), DATROWAY plus rilvegostomig demonstrated a confirmed objective response rate (ORR) of 68.2% (95% confidence interval [CI]: 45.1-86.1) and a disease control rate (DCR) of 95.5% (80% CI: 83.4-99.5). Median progression free survival (PFS) was not reached in the first-line setting and the PFS rate was 73.5% (95% CI: 46.5-88.4) at 12 months. As second-line treatment for patients who previously received platinum-based chemotherapy and no prior treatment with immunotherapy (n=18), DATROWAY plus rilvegostomig demonstrated a confirmed ORR of 38.9% (95% CI: 17.3-64.3) and a DCR of 83.3% (80% CI: 66.6-93.7). Median PFS was 12.5 months (95% CI: 4.2-NR) and the PFS rate was 60.0% (95% CI: 33.7–78.7) at 12 months. Median duration of response (DoR) was not yet reached in either setting.

"Despite recent advances in the treatment of metastatic urothelial cancer, there are limited treatment options in both the first-line and second-line settings and many patients still experience disease progression after first-line therapy," said Sun Young Rha, MD, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. "The response rates seen with TROPION-PanTumor03 across the first-line and second-line settings, including the disease control rate of 95.5% observed in the first-line setting, highlight the potential of datopotamab deruxtecan plus rilvegostomig and warrant further evaluation across lines of therapy."

The safety profile of DATROWAY plus rilvegostomig was consistent with the known safety profiles of each agent. Grade 3 or higher treatment-related adverse events (TRAEs) were observed in four of 22 patients (18.2%) receiving first-line treatment and in seven of 18 patients (38.9%) receiving second-line treatment. The most common grade 3 or higher TRAEs occurring in patients treated with DATROWAY plus rilvegostomig in the first-line (n=22) and second-line (n=18) settings, respectively, were increased amylase (13.6%, 16.7%), neutropenia (4.5%, 5.6%), stomatitis (0%, 5.6%), decreased appetite (0%, 5.6%) and anemia (0%, 5.6%). There was one (4.5%) interstitial lung disease (ILD) event adjudicated as drug-related in first-line and two (11.1%) in second-line setting with no grade 3 or higher ILD events observed.

Daiichi Sankyo has initiated the TROPION-Urothelial03 phase 2/3 trial evaluating DATROWAY plus platinum-based chemotherapy compared to gemcitabine and platinum-based chemotherapy in patients with metastatic urothelial carcinoma following progression during or after treatment with enfortumab vedotin in combination with pembrolizumab.

"The five-year survival rate for patients with metastatic urothelial cancer remains very low, underscoring the urgent need for new therapeutic options in this difficult-to-treat population," said Abderrahmane Laadem, MD, Head, Late-Stage Oncology Development, Daiichi Sankyo. "These results from TROPION-PanTumor03, coupled with results from TROPION-PanTumor01, support further clinical development of DATROWAY in urothelial cancer and we have initiated the TROPION-Urothelial03 phase 2/3 trial, our first pivotal trial outside of breast and lung cancer."

"These initial TROPION-PanTumor03 results offer further support for our strategy of combining the potency of DATROWAY with the dual PD-1 and TIGIT blockade of rilvegostomig to enhance patients’ immune responses and ultimately, improve outcomes," said Leora Horn, MD, MSC, FRCPC, Senior Vice President, Late Development Oncology, AstraZeneca. "We are encouraged by the responses observed in patients with metastatic urothelial cancer and hope to further evaluate this combination in the early-line setting."

In TROPION-PanTumor03, patients were enrolled across seven sub-studies that evaluated DATROWAY as monotherapy or in combination with other approved or investigational cancer medicines. In a sub-study evaluating patients with locally advanced or metastatic urothelial cancer (sub-study 6, cohort 6B [n=40]), patients received DATROWAY in combination with rilvegostomig in either the first-line setting (cisplatin ineligible patients with no prior systemic therapy, or progression more than 12 months after neoadjuvant or adjuvant therapy) or the second-line setting (previous platinum-based chemotherapy in the locally advanced or metastatic setting, or progression less than 12 months after platinum-based neoadjuvant or adjuvant therapy). Of the second-line patients who were not previously treated with immunotherapy (n=18), six had previous treatment in the adjuvant or neoadjuvant setting with progression within 12 months and 12 had been treated in the metastatic setting. Median duration of follow-up was 10.8 months and 9.7 months in the first-line and second-line setting, respectively.

Summary of Sub-study 6, Cohort 6B of TROPION-PanTumor03 Efficacy Results

Efficacy Measure

First-Line Subset (n=22)

Second-Line Subset (n=18)

Confirmed ORR,i,ii (%) (95% CI)

68.2% (45.1–86.1)

38.9% (17.3–64.3)

CR, n (%)

1 (4.5%)

0

PR, n (%)

14 (63.6%)

7 (38.9%)

SD, n (%)

6 (27.3%)

8 (44.4%)

PD, n (%)

1 (4.6%)iii

3 (16%)

DCR at 12 weeks,iv (%) (80% CI)

95.5% (83.4–99.5)

83.3% (66.6–93.7)

DoR, median ii (months) (95% CI)

NR (9.4 months–NR)

NR (6.9 months–NR)

PFS medianii (months) (95% CI)

NR (10.8 months–NR)

12.5 months (4.2 months–NR)

CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; NR, not reached; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease
iORR is CR+ PR
iiAs assessed by investigator
iiiPatient has no post-baseline assessment and died less than 13 weeks after first dose
ivProportion of patients who had achieved a CR or PR in the first 13 weeks or who had SD for at least 11 weeks after start of treatment as assessed by investigator

About TROPION-PanTumor03
TROPION-PanTumor03 is a global, multicenter, multi-cohort, open-label, phase 2 trial evaluating the efficacy and safety of DATROWAY as monotherapy and in combination with various approved or investigational cancer medicines across seven sub-studies in several metastatic solid cancers, including endometrial, gastric, prostate, ovarian, colorectal, urothelial and biliary tract cancer.

Cohort 6B is evaluating DATROWAY (6 mg/kg) plus rilvegostomig as first-line and second-line combination therapies in patients with locally advanced or metastatic urothelial cancer. The primary endpoint is ORR as assessed by investigator as well as safety and tolerability. Secondary endpoints include investigator-assessed DCR, DoR, PFS as assessed by investigator as well as pharmacokinetics.

TROPION-PanTumor03 will enroll approximately 580 patients across all sub-studies in Asia, Europe and North America. For more information visit ClinicalTrials.gov.

Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN).

About TROPION-Urothelial03
TROPION-Urothelial03 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of DATROWAY plus platinum-based chemotherapy (carboplatin or cisplatin) versus gemcitabine plus platinum-based chemotherapy in patients with locally advanced or metastatic urothelial carcinoma with disease progression during or after enfortumab vedotin plus pembrolizumab combination treatment. The phase 2 part of the trial will determine the recommended dose of DATROWAY (4 mg/kg or 6 mg/kg) in combination with carboplatin or cisplatin. The phase 3 part will evaluate the efficacy and safety of DATROWAY at the recommended dose plus carboplatin or cisplatin versus gemcitabine plus carboplatin or cisplatin.

The primary endpoint of the phase 2 part of TROPION-Urothelial03 is ORR assessed by investigator. Secondary endpoints include DoR, PFS, DCR, time to response (TTR), overall survival (OS) and safety.

The dual primary endpoints of the phase 3 part of TROPION-Urothelial03 are PFS assessed by blinded independent central review (BICR) and OS. Secondary endpoints include PFS by investigator, ORR, DoR, TTR, DCR, each assessed by BICR and by investigator, and safety.

TROPION-Urothelial03 will enroll approximately 630 patients at sites in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

About Urothelial (Bladder) Cancer
More than 610,000 bladder cancer cases were diagnosed globally in 2022.1 The most common type of bladder cancer is urothelial cancer, accounting for approximately 90% of cases.2 While the five-year survival rate for localized bladder cancer is more than 70%, survival decreases to approximately 9% in the metastatic setting.3,4

While targeted therapies have improved outcomes in the first-line metastatic setting, disease progression is common and treatment options in the second-line setting are limited.5

TROP2 is a protein broadly expressed in several solid tumors including urothelial cancer.6 TROP2 expression is positively correlated with disease severity in patients with urothelial cancer.7

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 is approved in more than 35 countries/regions 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 the 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 the 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, triple negative breast cancer and urothelial cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other cancer treatments in various settings.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and DATROWAY.

About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.

The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.

The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.

Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.

DATROWAY U.S. Important Safety Information
Indications

DATROWAY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of:

adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy.
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (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.
Contraindications
None.

Warnings and Precautions
Interstitial Lung Disease/Pneumonitis
DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis.

Locally Advanced or Metastatic NSCLC
In the pooled safety population of 484 patients with NSCLC from TROPION-Lung01, TROPION-Lung05, and TROPION-PanTumor01, ILD/pneumonitis occurred in 7% of patients treated with DATROWAY, including 0.6% of patients with Grade 3 and 0.4% with Grade 4. There were 8 (1.7%) fatal cases. The median time to onset for ILD was 1.4 months (range: 0.2 months to 9 months). Eleven patients (2.3%) had DATROWAY withheld and 20 patients (4.1%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 79% (26/33) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 45% of patients.

Unresectable or Metastatic Breast Cancer
In the pooled safety population of 443 patients with breast cancer from TROPION-Breast01 and TROPION-PanTumor01, ILD/pneumonitis occurred in 3.6% of patients treated with DATROWAY, including 0.7% of patients with Grade 3. There was one fatal case (0.2%). The median time to onset for ILD was 2.8 months (range: 1.1 months to 10.8 months). Four patients (0.9%) had DATROWAY withheld and 7 patients (1.6%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 60% (9/15) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 40% of patients.

Patients were excluded from clinical studies for a history of ILD/pneumonitis requiring treatment with steroids or for ongoing ILD/pneumonitis.

Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if ≥Grade 2 ILD/pneumonitis is confirmed.

Ocular Adverse Reactions
DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision.

In the pooled safety population, ocular adverse reactions occurred in 36% of patients treated with DATROWAY. Twenty patients (2.2%) experienced Grade 3 ocular adverse reactions, which included keratitis, dry eye, and blurred vision, and one patient experienced a Grade 4 ocular adverse reaction of conjunctival hemorrhage. The most common (≥5%) ocular adverse reactions were dry eye (17%), keratitis (14%), and increased lacrimation (7%). The median time to onset for ocular adverse reactions was 2.3 months (range: 0.03 months to 23.2 months). Of the patients who experienced ocular adverse reactions, 39% had complete resolution, and 10% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to dosage interruption in 3.6% of patients, dosage reductions in 2.5% of patients, and permanent discontinuation of DATROWAY in 1% of patients.

Patients with clinically significant corneal disease were excluded from clinical studies.

Advise patients to use preservative-free lubricant eye drops several times daily for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional.

Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at treatment initiation, annually while on treatment, at end of treatment, and as clinically indicated.

Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, withhold, reduce the dose, or permanently discontinue DATROWAY based on severity.

Stomatitis
DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis.

In the pooled safety population, stomatitis occurred in 63% of patients treated with DATROWAY, including 8% of patients with Grade 3 events and one patient with a Grade 4 reaction. The median time to first onset of stomatitis was 0.5 months (range: 0.03 months to 18.6 months). Stomatitis led to dosage interruption in 6% of patients, dosage reductions in 11% of patients, and permanent discontinuation of DATROWAY in 0.5% of patients.

In patients who received DATROWAY in TROPION-Breast01, 39% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment.

Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY.

Monitor patients for signs and symptoms of stomatitis. If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue DATROWAY.

Embryo-Fetal Toxicity
Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells.

Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose.

Adverse Reactions
The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY in 927 patients as a single agent at 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. This included 137 patients with NSCLC in TROPION-Lung05, 297 patients with NSCLC in TROPION-Lung01, 360 patients with HR-positive, HER2-negative breast cancer in TROPION-Breast01, and 50 patients with NSCLC and 83 patients with breast cancer in TROPION-PanTumor01 (NCT03401385). Among 927 patients who received DATROWAY, 45% were exposed for 6 months or longer and 19% were exposed for greater than one year. In this pooled safety population, the most common (≥20%) adverse reactions were stomatitis (63%), nausea (52%), fatigue (45%), alopecia (38%), constipation (28%), decreased appetite (23%), rash (23%), vomiting (22%), and musculoskeletal pain (20%). In this pooled safety population, the most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (9%) and decreased hemoglobin (3.5%).

Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer
TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01

The safety of DATROWAY was evaluated in 125 patients with EGFR-mutated NSCLC who received DATROWAY 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity in TROPION-Lung05 and TROPION-Lung01 as well as TROPION-PanTumor01 (NCT03401385). Among these patients, the median duration of treatment was 6.1 months (range 0.7 months to 41.7 months).

The median age was 63 years (range: 36 to 81), 56% of patients were <65 years, 62% of patients were female; 66% were Asian, 26% were White, 0.8% were Black, 6% were other races; and 2.4% were of Hispanic ethnicity.

Serious adverse reactions occurred in 26% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were COVID-19 (4%), stomatitis (2.4%), and pneumonia (1.6%). Fatal adverse reactions occurred in 1.6% of patients who received DATROWAY, due to death not otherwise specified.

Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >1% of patients included ILD/pneumonitis (2.4%) and abnormal hepatic function (1.6%).

Dosage interruptions of DATROWAY due to an adverse reaction occurred in 43% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (13%), stomatitis (7%), fatigue (6%), pneumonia (4%), anemia (2.4%), amylase increased (2.4%), keratitis (2.4%), ILD/pneumonitis (1.6%), decreased appetite (1.6%), dyspnea (1.6%), rash (1.6%), and infusion-related reaction (1.6%).

Dose reductions of DATROWAY due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (14%), keratitis (1.6%), fatigue (1.6%), decreased weight (1.6%) and COVID-19 (1.6%).

The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis (71%), nausea (50%), alopecia (49%), fatigue (42%), decreased hemoglobin (34%), decreased lymphocytes (32%), constipation (31%), increased calcium (31%), increased AST (28%), decreased white blood cell count (27%), increased lactate dehydrogenase (23%), musculoskeletal pain (22%), decreased appetite (20%), increased ALT (20%), and rash (20%).

Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included dry skin, blurred vision, abdominal pain, conjunctivitis, dry mouth, ILD/pneumonitis, skin hyperpigmentation, increased lacrimation, and visual impairment.

Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer
TROPION-Breast01

The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast01. DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 6.7 months (range: 0.7 months to 16.1 months) for patients who received DATROWAY.

Serious adverse reactions occurred in 15% of patients who received DATROWAY. Serious adverse reactions in >0.5% of patients who received DATROWAY were urinary tract infection (1.9%), COVID-19 infection (1.7%), ILD/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of patients who received DATROWAY and were due to ILD/pneumonitis.

Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 3.1% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (1.7%) and fatigue (0.6%).

Dosage interruptions of DATROWAY due to an adverse reaction occurred in 22% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (3.3%), infusion-related reaction (1.4%), ILD/pneumonitis (1.9%), stomatitis (1.9%), fatigue (1.7%), keratitis (1.4%), acute kidney injury (1.1%), and pneumonia (1.1%).

Dose reductions of DATROWAY due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (13%), fatigue (3.1%), nausea (2.5%), and weight decrease (1.9%).

The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis (59%), nausea (56%), fatigue (44%), decreased leukocytes (41%), decreased calcium (39%), alopecia (38%), decreased lymphocytes (36%), decreased hemoglobin (35%), constipation (34%), decreased neutrophils (30%), dry eye (27%), vomiting (24%), increased ALT (24%), keratitis (24%), increased AST (23%), and increased alkaline phosphatase (23%).

Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions (including bronchospasm), ILD/pneumonitis, headache, pruritus, dry skin, dry mouth, conjunctivitis, blepharitis, meibomian gland dysfunction, blurred vision, increased lacrimation, photophobia, visual impairment, skin hyperpigmentation, and madarosis.

Use in Specific Populations

Pregnancy: Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells. There are no available data on the use of DATROWAY in pregnant women to inform a drug-associated risk. Advise patients of the potential risks to a fetus.
Lactation: There are no data regarding the presence of datopotamab deruxtecan-dlnk or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with DATROWAY and for 1 month after the last dose.
Females and Males of Reproductive Potential: Pregnancy Testing: Verify pregnancy status of females of reproductive potential prior to initiation of DATROWAY. Contraception: Females: Advise females of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Males: Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose. Infertility: Based on findings in animal toxicity studies, DATROWAY may impair male and female reproductive function and fertility. The effects on reproductive organs in animals were irreversible.
Pediatric Use: Safety and effectiveness of DATROWAY have not been established in pediatric patients.
Geriatric Use: Of the 125 patients with EGFR-mutated NSCLC in TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 treated with DATROWAY 6 mg/kg, 44% were ≥65 years of age and 10% were ≥75 years of age. No clinically meaningful differences in efficacy and safety were observed between patients ≥65 years of age versus younger patients. Of the 365 patients in TROPION-Breast01 treated with DATROWAY 6 mg/kg, 25% were ≥65 years of age and 5% were ≥75 years of age. Grade ≥3 and serious adverse reactions were more common in patients ≥65 years (42% and 25%, respectively) compared to patients <65 years (33% and 15%, respectively). In TROPION-Breast01, no other meaningful differences in safety or efficacy were observed between patients ≥65 years of age versus younger patients.
Renal Impairment: A higher incidence of ILD/pneumonitis has been observed in patients with mild and moderate renal impairment (creatinine clearance [CLcr] 30 to <90 mL/min). Monitor patients with renal impairment for increased adverse reactions, including respiratory reactions. No dosage adjustment is recommended in patients with mild to moderate renal impairment. The effect of severe renal impairment (CLcr <30 mL/min) on the pharmacokinetics of datopotamab deruxtecan-dlnk or DXd is unknown.
Hepatic Impairment: No dosage adjustment is recommended in patients with mild hepatic impairment (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST). Limited data are available in patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST). Monitor patients with moderate hepatic impairment for increased adverse reactions. The recommended dosage of DATROWAY has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).

(Press release, Daiichi Sankyo, OCT 17, 2025, View Source [SID1234656743])