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ENHERTU® Approved in China as the First and Only HER2 Directed ADC for the Second-Line Treatment of Patients with HER2 Positive Metastatic Gastric Cancer

On January 22, 2026 Daiichi Sankyo reported that ENHERTU (trastuzumab deruxtecan) has been approved in China for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received one prior trastuzumab based regimen. ENHERTU previously received conditional approval for third-line or later treatment based on laterline phase 2 data.

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

More than one third of the global cases of gastric cancer occur in China, with about 65% of patients presenting with advanced disease at the time of diagnosis.1,2,3 Approximately 359,000 cases of gastric cancer and 260,000 deaths were reported in China in 2022.1 About one in five gastric cancers are considered HER2 positive. 4,5 Prior to the results of DESTINY-Gastric04, no other HER2 directed medicine has demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial.

The approval of ENHERTU by China’s National Medical Products Administration (NMPA) is based on results from the DESTINY-Gastric04 phase 3 trial presented as a late-breaking oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO25) Annual Meeting and simultaneously published in The New England Journal of Medicine. The China Center for Drug Evaluation (CDE) granted Breakthrough Therapy Designation for ENHERTU for the second-line gastric cancer indication in 2020 due to efficacy data from early trials and the unmet clinical need. ENHERTU also was granted Priority Review by the CDE in this setting, enabling approval in China in approximately six months.

In DESTINY-Gastric04, ENHERTU demonstrated a 30% reduction in risk of death compared to ramucirumab plus paclitaxel in patients with second-line HER2 positive unresectable and/or metastatic gastric or GEJ adenocarcinoma (hazard ratio [HR]: 0.70; confidence interval [CI]: 0.55-0.90; p=0.0044). Median overall survival (OS) was 14.7 months with ENHERTU (n=246; 95% CI: 12.1-16.6) compared to 11.4 months with ramucirumab plus paclitaxel (n=248; 95% CI: 9.9-15.5).

In the secondary endpoint analysis of progression-free survival (PFS), ENHERTU demonstrated a 26% reduction in the risk of disease progression or death versus ramucirumab plus paclitaxel (HR: 0.74; 95% CI: 0.59-0.92; p=0.0074) as assessed by investigator. Median PFS was 6.7 months (95% CI: 5.6-7.1) with ENHERTU versus 5.6 months (95% CI: 4.9-5.8) with ramucirumab plus paclitaxel. A confirmed objective response rate (ORR) of 44.3% (95% CI: 37.8-50.9) was seen in patients treated with ENHERTU with seven complete responses (CR) and 97 partial responses (PR) versus a confirmed ORR of 29.1% (95% CI: 23.4- 35.3) with three CRs and 66 PRs in the ramucirumab plus paclitaxel arm (p=0.0006). Median duration of response (DOR) was 7.4 months (95% CI: 5.7-10.1) in the ENHERTU arm and 5.3 months (95% CI: 4.1- 5.7) in the ramucirumab plus paclitaxel arm.

"Most patients with gastric cancer are diagnosed with advanced disease, which has a low survival rate and is particularly challenging to treat," said Lin Shen, MD, Director of the Department of Gastrointestinal Oncology, Peking University Cancer Hospital and lead investigator of the DESTINY-Gastric04 trial in China. "This approval is an important milestone for the clinical community in China, addressing a critical gap in second-line targeted therapy for HER2 positive gastric cancer. This development is driving a paradigm shift from chemotherapy towards precision therapy in the second-line setting for patients with HER2 positive gastric cancer. At the same time, it provides clinicians with a powerful new option capable of significantly extending patient survival. We will be able to bring this innovative treatment to earlier lines of therapy, benefit a broader patient population, improve long-term outcomes and achieve longer survival."

"This sixth approval for ENHERTU in China in less than three years fully demonstrates the potential of this innovative medicine to make significant contributions in clinical practice," said Michio Hayashi, China President, Daiichi Sankyo. "DESTINY-Gastric04 is the first randomized phase 3 trial ever to show a survival benefit in the second-line HER2 positive metastatic gastric cancer setting and also confirmed the results of the DESTINY-Gastric01 and DESTINY-Gastric06 trials."

"ENHERTU is already established in China in the third-line or later treatment setting for patients with HER2 positive metastatic gastric cancer and this approval brings this important medicine to an earlier line of therapy," said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. "This latest approval in China underscores our commitment to bringing ENHERTU to patients in earlier treatment settings to improve outcomes and expand the number of people who may benefit."

The safety profile of ENHERTU in DESTINY-Gastric04 was consistent with previous clinical trials with no new safety concerns identified. The most common grade 3 or grade 4 adverse reactions from a pooled safety population receiving at least one dose of ENHERTU 6.4 mg/kg (n=1,133) across multiple tumor types in clinical studies were nausea (64.3%), fatigue (57.3%), anemia (47.9%), decreased appetite (46.8%), neutropenia (45.9%), vomiting (34.7%), diarrhea (33.0%), thrombocytopenia (32.9%), leukopenia (31.2%), alopecia (29.0%), constipation (28.2%) and increased transaminases (26.4%). Grade 5 adverse reactions occurred in 2.2% of patients, including interstitial lung disease (ILD; 1.6%). Discontinuation of treatment due to an adverse reaction occurred in 13.2% of patients. The most frequent adverse reaction associated with permanent discontinuation was ILD (9.8%).

ENHERTU also is being evaluated as a potential first-line treatment for HER2 positive metastatic gastric cancer through two ongoing phase 3 trials – DESTINY-Gastric05 and ARTEMIDE-Gastric01.

About DESTINY-Gastric04

DESTINY-Gastric04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg) versus ramucirumab and paclitaxel in patients with HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen.

The primary endpoint is OS. Secondary endpoints include investigator-assessed PFS, ORR, DOR, disease control rate and safety.

In March 2025, an Independent Data Monitoring Committee recommended unblinding DESTINY-Gastric04 based on the superior efficacy of ENHERTU seen at a planned interim analysis.

DESTINY-Gastric04 enrolled 494 patients in Asia, Europe and South America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Gastric Cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancerrelated death, with a five-year global survival rate of 5% to 10% for advanced or metastatic disease.2,7 Approximately one million cases of gastric cancer were diagnosed in 2022.

Incidence rates for gastric cancer are markedly higher in eastern Asia, particularly in China where more than one third of all global cases occur. 1,2 Gastric cancer is the fifth most common cancer in China with about 359,000 new cases diagnosed in 2022.1 Additionally, it is the third leading cause of cancer-related death in China, with approximately 260,000 deaths reported in 2022.1 Approximately 65% of patients in China present with advanced disease at the time of diagnosis.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer.8 Approximately one in five gastric cancers are considered HER2 positive. 4,5 Recommended first-line treatment in China for HER2 positive advanced or metastatic gastric cancer is combination chemotherapy and trastuzumab, an anti-HER2 medicine, with or without pembrolizumab. 9 For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, subsequent anti-HER2 treatment options are limited.

Prior to the results of the DESTINY-Gastric04 trial of ENHERTU, no other HER2 directed medicine had demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial.

About ENHERTU

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

ENHERTU (5.4 mg/kg) in combination with pertuzumab is approved in the U.S. as a first-line treatment for adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test, based on the results from the DESTINY-Breast09 trial.

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

ENHERTU (5.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

ENHERTU (5.4 mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 80 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric04 trials.

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

About the ENHERTU Clinical Development Program

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

(Press release, Daiichi Sankyo, JAN 22, 2026, View Source [SID1234665023])

Guardant Health Receives FDA Approval for Guardant360® CDx as Companion Diagnostic for BRAFTOVI® (encorafenib) Combination in Patients with BRAF V600E-Mutant Metastatic Colorectal Cancer

On January 22, 2026 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that the U.S. Food and Drug Administration (FDA) has approved Guardant360 CDx as a companion diagnostic to identify patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC) who may benefit from treatment with BRAFTOVI (encorafenib) in combination with cetuximab and chemotherapy in accordance with the approved product labeling.

The accelerated approval was supported by data from Pfizer’s Phase 3 BREAKWATER trial, which evaluated encorafenib-based regimens in previously untreated patients with BRAF-mutated metastatic colorectal cancer mCRC. The study showed that treatment with encorafenib and cetuximab plus mFOLFOX6 chemotherapy significantly improved objective response rate, progression-free and overall survival compared with standard care, underscoring the importance of early genomic testing to guide targeted therapy.

Guardant360 CDx expands access to non-invasive genomic testing for this high-risk patient population. Using a simple blood draw to detect BRAF V600E and other clinically relevant genetic alterations, the test helps clinicians quickly identify patients eligible for FDA-approved treatments, enabling timely treatment decisions when tumor tissue is unavailable, insufficient, or when rapid initiation of therapy is clinically necessary.

"This latest approval highlights the growing impact of liquid biopsy across advanced cancer care and underscores the utility of Guardant360 CDx in enabling precision therapy selection for patients with diverse, hard-to-treat tumors including aggressive colorectal cancer," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "With multiple FDA-cleared companion diagnostic claims across lung and breast cancer, and now colorectal cancer, and the ability to comprehensively profile tumor genomics from a simple blood draw, Guardant360 CDx is helping clinicians match patients to the right targeted therapies faster and more effectively."

Key highlights of the BREAKWATER trial include:

Demonstrated significant improvement in overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) for patients treated with encorafenib plus cetuximab with mFOLFOX6 chemotherapy.
Guardant360 CDx enabled rapid ctDNA analysis for treatment selection and resistance monitoring.
The study supports the importance of early, comprehensive genomic profiling to improve outcomes in mCRC.
Colorectal cancer remains the second-leading cause of cancer-related deaths in the U.S., with BRAF V600E mutations present in approximately 8 to 10 percent of mCRC cases.1 The mutation is a molecularly distinct and aggressive subtype of mCRC with poor prognosis and limited treatment options. Early identification of this mutation is critical to guiding patients to more effective, targeted therapies. Guardant360 CDx offers a convenient and accessible method for detecting this actionable biomarker, especially when tissue samples are unavailable or inadequate for testing.

This latest FDA approval for Guardant 360 CDx marks the 25th companion diagnostic indication across multiple tumor types and builds on the platform’s increasing clinical utility and broad coverage by Medicare and commercial payers, representing more than 300 million covered lives.

About Guardant360 CDx

Guardant360 CDx is the first FDA-approved liquid biopsy for comprehensive genomic profiling. It detects multiple genomic alterations across all solid tumors and is approved as a companion diagnostic for therapies in non-small cell lung cancer, breast cancer, and now colorectal cancer. For more information, visit Guardant360 CDx.

(Press release, Guardant Health, JAN 22, 2026, View Source [SID1234662178])

Ellipses In-Licenses First-in-Class B7H3 Antibody Drug Conjugate From China

On January 22, 2026 Ellipses Pharma Limited ("Ellipses"), a clinical-stage oncology drug development company with a pipeline of innovative programmes, reported that it has entered into a collaboration and licence agreement with Innolake Biopharm Co. Ltd ("Innolake") to develop a clinical stage first-in-class antibody drug conjugate (ADC).

Under the partnership, Ellipses gains rights to develop a B7H3 targeted ADC with an eribulin payload (ILB-3101) worldwide excluding greater China. ILB-3101 has the potential to treat multiple tumour types and to address resistance to topoisomerase-1 based ADCs. ILB-3101 is designated as EP0028 by Ellipses.

Ellipses and Innolake will collaborate closely on the development of ILB-3101/EP0028, which is currently in a Phase 1 trial in China sponsored by Innolake. Ellipses will initiate a Phase 1 clinical trial in the US with expansion to Europe and other territories following relevant regulatory approvals.

EP0028 is an important addition to Ellipses’ clinical-stage pipeline and is the second programme Ellipses has in-licensed from an innovative biotech company based in China. The first programme, EP0031, is a next-generation selective RET inhibitor developed by Kelun Biotech, which Ellipses is currently advancing through Phase 2 trials.

Professor Sir Chris Evans, OBE, Executive Chair of Ellipses, commented: "We are delighted to bring this differentiated ADC into our pipeline. EP0028 has the potential to address unmet needs in a range of indications and further strengthens our strategy to develop Chinese originated assets in the West."

Professor Tobias Arkenau, Global Head of Drug Development and Chief Medical Officer of Ellipses, commented: "Ellipses’ decision to in-license EP0028 is a significant milestone for us in continuing our mission to develop new cancer drugs for patients with high unmet clinical needs. Our collaboration with Innolake is another great opportunity to develop innovative cancer drugs globally, robustly and at speed to serve our communities."

Mingde Xia, CEO of Innolake, commented: "This partnership is a great validation of our technology and capabilities. Having advanced ILB-3101 from early discovery through to the clinic, we are delighted to collaborate with Ellipses and look forward to bringing this innovative therapy to patients worldwide."

(Press release, Ellipses Pharma, JAN 22, 2026, View Source [SID1234662177])

CorriXR Therapeutics Announces Publication of Additional Preclinical Data Corroborating Ability of NRF2 Knockout to Restore Chemosensitivity in Solid Tumors

On January 22, 2026 CorriXR Therapeutics, an oncology focused biotherapeutics company developing genetic medicines to overcome drug resistance in solid tumors, reported that its novel CRISPR-directed disruption of the transcription factor NRF2 can restore chemosensitivity in head and neck and esophageal squamous cell carcinoma models. The preclinical data were published in Molecular Therapy Oncology. The study, conducted in collaboration with scientists at ChristianaCare’s Gene Editing Institute (GEI), reinforces CorriXR’s previously reported data in lung cancer models and highlights how CRISPR targeting of NRF2 can disrupt tumor cells’ protective mechanisms and potentially boost patients’ bodies’ ability to respond more effectively to standard chemotherapy.

"For patients with solid tumor cancers, once their tumors become resistant to chemotherapy, treatment options narrow and are often more toxic to them," said Eric B Kmiec, Ph.D., Founder and Chief Executive Officer of CorriXR Therapeutics and Executive Director of GEI. "These data from CorriXR’s first-in-class editing approach suggest that by precisely disrupting NRF2, we may be able to reopen the window to standard treatments and potentially do so at lower doses; this could translate into better control of disease with fewer side effects for patients."

NRF2 is a master regulator of cellular stress responses and a well-established driver of treatment resistance in multiple cancers, making it an attractive but historically "undruggable" target for therapeutic intervention. CorriXR is advancing essential studies to support an IND filing in head and neck squamous cell carcinoma (HNSCC) as a potential first clinical indication.

Head and neck cancer, 90% of which is HNSCC, is the seventh most diagnosed cancer worldwide, with annual incidence predicted to reach one million new cases by 2030. With 50% of patients experiencing recurrence within two years, there is a significant need for new approaches that can overcome resistance to current treatment paradigms. CorriXR anticipates completion of additional in vivo studies in HNSCC in combination with chemotherapy and radiation in the first half of 2026.

Study Overview

Researchers used CRISPR/Cas9 complexes to disrupt NRF2 in hypopharyngeal (FaDu) and esophageal (KYSE‑410) squamous cell carcinoma cells and then assessed gene editing outcomes, NRF2 pathway activity, and response to cisplatin and 5‑fluorouracil. Key study findings include:

High levels of on-target editing produced substantial reductions in NRF2 protein levels, decreased expression of downstream stress response genes, and significantly restored chemosensitivity.
Genetic disruption of NRF2 alone is sufficient to disrupt its ability to activate the genes that defend tumor cells.
Enhanced chemosensitivity after NRF2 disruption persisted over time, creating a treatment window for combination therapy.
The choice of CRISPR editing site on NRF2 influences both the functional impact on NRF2 and which cells are affected by the edit. Editing that disrupts a functional binding domain enables an approach that is agnostic to and independent of genetic mutations in the cancer cells.
"These findings complement previously published data from CorriXR and GEI showing that tumor-specific NRF2 editing in lung cancer models can resensitize tumors to standard chemotherapy and reduce tumor growth in vivo, thereby reinforcing NRF2 as a central node for overcoming drug resistance," said Natalia Rivera-Torres, Ph.D., lead author of the study and Associate Director of Research at GEI.

Kmiec added, "What is most encouraging about this work is that we are giving existing drugs a second chance to work in tumors that have learned how to evade them, enabling patients to benefit more, and longer, from proven regimens, with a better quality of life."

(Press release, CorriXR Therapeutics, JAN 22, 2026, View Source [SID1234662176])

Israel Cancer Research Fund and Cancer Research Institute Announce Co-Funding of Grant to Address Immunotherapy Resistance in Melanoma

On January 22, 2026 Israel Cancer Research Fund (ICRF) and the Cancer Research Institute (CRI) reported to have partnered on a new award, the ICRF-CRI Immunotherapy Collaborative Project Grant, given to Dr. Asaf Madi, PhD, of Tel Aviv University. Dr. Madi was awarded $180,000 over a three-year period to support his research on refining tumor-infiltrating lymphocyte (TIL) therapy to predict response and overcome drug resistance in melanoma.

"We are honored to once again partner with CRI, a world-class immunotherapy research organization, on this cutting-edge project," said Alan Herman, ICRF’s Executive Director. "There is a clear, unmet need for personalized treatments like TIL therapy, and Dr. Madi’s research into adoptive cell transfer could offer new hope to melanoma patients in urgent need of better options."

Adoptive cell transfer (ACT) using TILs is a promising personalized immunotherapy for melanoma, shown to improve survival in advanced cases. However, many patients do not respond, and others develop resistance, limiting the long-term effectiveness of this approach. Dr. Madi’s research aims to address these challenges by identifying predictive biomarkers, uncovering mechanisms of tumor resistance, and optimizing TIL selection and expansion to improve therapeutic outcomes.

Dr. Madi and his team are studying the gene circuits that program immune cells, controlling their differentiation, activation, and regulation. By examining how T cells behave in tumors, particularly following immunotherapy, they aim to determine why some T cells sustain anti-tumor activity while others become exhausted or suppressed. Insights from this work will guide the selection and engineering of more potent TIL populations capable of durable tumor targeting and generating long-term immune memory, reducing the risk of cancer recurrence.

"This collaboration reflects what progress in immunotherapy really looks like—bringing together partners, data, and discovery to tackle resistance head-on," said Alicia Zhou, PhD, CEO of CRI. "By understanding why some immune cells persist while others fail, Dr. Madi’s work moves us closer to making personalized cell therapies like TILs more reliable, more durable, and more transformative for patients with melanoma."

Melanoma is the deadliest form of skin cancer. In the U.S. alone, over 100,000 new cases are diagnosed each year, and advanced melanoma can be resistant to standard treatments. Because it can spread quickly and evade therapies, developing new, effective treatments is critical to improve survival and offer hope to patients and their families worldwide.

Dr. Asaf Madi earned his Ph.D. in computational immunology at Tel Aviv University in collaboration with the Weizmann Institute of Science, studying B cell and T cell repertoires. He then completed a postdoctoral fellowship at Harvard Medical School and the Broad Institute, focusing on T-cell differentiation and cancer immunology. Dr. Madi then returned to Tel Aviv University, where he is now an Associate Professor in the Department of Pathology, leading a team that drives the development of novel anti-cancer therapies.

(Press release, Cancer Research Institute, JAN 22, 2026, View Source [SID1234662175])