TARGETED THERAPY FOR
GASTRIC CANCER
The complete landscape of targeted therapy in gastric cancer โ from HER2-directed trastuzumab and T-DXd through CLDN18.2-directed zolbetuximab to VEGFR2 inhibition and emerging FGFR2b and novel targets being investigated in Chinese clinical trials.
analyticsAt a Glance
- check_circleGastric cancer targeted therapy has expanded from one target (HER2) to four actionable biomarkers in routine practice
- check_circleCLDN18.2 is now the largest novel biomarker-defined group โ zolbetuximab NMPA-approved in China 2024
- check_circleFGFR2b, VEGFR2, and emerging ADC targets expand precision medicine options beyond HER2
- check_circleCancerFax coordinates targeted therapy access at specialist Chinese gastric cancer centres
The Targeted Therapy Revolution in Gastric Cancer
Gastric cancer was once considered a molecularly undifferentiated disease treated with generic platinum-fluoropyrimidine chemotherapy. This view has been comprehensively revised. Since the ToGA trial established HER2-directed therapy in 2010, the gastric cancer molecular landscape has been systematically characterised โ revealing distinct, actionable subgroups that now define the first-line and second-line treatment landscape.
โThe question is no longer 'does this patient have gastric cancer?' โ it is 'which molecular subtype does this patient have, and which targeted agents address that subtype?'โ
From One Target to Four
In 2010, HER2 was the only actionable target in gastric cancer. By 2025, four clinically actionable biomarkers guide treatment selection: HER2 (trastuzumab, T-DXd), PD-L1/MSI (checkpoint inhibitors), CLDN18.2 (zolbetuximab), and VEGFR2 (ramucirumab). FGFR2b and additional targets are advancing through trials.
Biomarker Testing Is Now Mandatory
Complete biomarker profiling at the point of advanced/metastatic gastric cancer diagnosis is now the standard of care. Missing a biomarker result at diagnosis can mean missing the most effective first-line treatment โ a clinical error with measurable survival consequences.
Gastric Cancer Targeted Agents by Biomarker and Line
A comprehensive reference of approved and trial-available targeted agents in gastric cancer โ organised by biomarker, line of therapy, and availability in China.
| Biomarker | Target / Agent | Line | Evidence Basis | China Availability |
|---|---|---|---|---|
| HER2 (IHC 3+ or 2+/ISH+) | Trastuzumab + chemo | 1st line | ToGA Phase III (Lancet 2010) | Standard โ all major centres |
| HER2 (IHC 3+ or 2+) | T-DXd (trastuzumab deruxtecan) | 2nd line | DESTINY-Gastric01/02 | NMPA approved |
| HER2-overexpressing | RC48 (disitamab vedotin) | 2nd line | RC48-C007 Phase II/III | NMPA approved โ China domestic |
| CLDN18.2 โฅ75% cells 2+/3+ / HER2โ | Zolbetuximab + FOLFOX/CAPOX | 1st line | SPOTLIGHT + GLOW Phase III | NMPA approved 2024 |
| VEGFR2 (all advanced gastric) | Ramucirumab ยฑ paclitaxel | 2nd line | REGARD + RAINBOW Phase III | Available at major centres |
| FGFR2b overexpression | Bemarituzumab + mFOLFOX6 | 1st line (trial) | BEMA-1 Phase II; FORTITUDE Phase III | Active trials at Chinese centres |
| HER2+ (bispecific novel) | Zanidatamab (ZW25) | 2nd line+ (trial) | Phase I/II active | Trial access at Chinese centres |
| CLDN18.2+ (CAR-T target) | CT-041 tanajducel (CAR-T) | 2nd/3rd (trial) | Phase I/II (CARsgen) | Trial at CARsgen-affiliated centres |
How Many Gastric Cancer Patients Are Eligible for Each Targeted Therapy?
An indicative overview of the approximate proportion of advanced gastric cancer patients carrying each targetable biomarker โ illustrating the potential reach of each targeted therapy approach.
Biomarker Prevalence in Advanced Gastric Cancer (Approximate)
Approximate prevalence estimates from published gastric cancer biomarker studies and trial eligibility data. Overlap exists (e.g. CLDN18.2/HER2 co-positive ~8โ10%).
- PD-L1 CPS โฅ5 (nivolumab eligible)~60โ65%
- CLDN18.2 high (โฅ75% cells 2+/3+)~38โ40%
- MSI-H/dMMR (pembrolizumab monotherapy)~5โ10%
- HER2 positive (IHC 3+ or 2+/ISH+)~15โ20%
- FGFR2b overexpression (bemarituzumab)~7โ10%
The Recommended Biomarker Testing Pathway at Diagnosis
Complete biomarker testing at diagnosis is essential for gastric cancer treatment planning. This is the recommended sequence and rationale.
- 1
HER2 IHC + ISH
First and most urgent biomarker test. HER2 positivity (IHC 3+ or IHC 2+/ISH+) defines eligibility for trastuzumab in first-line and T-DXd at second-line. Use gastric cancer-specific IHC scoring criteria โ not breast cancer criteria.
- 2
CLDN18.2 IHC
Claudin 18.2 testing using the validated SPOTLIGHT/GLOW scoring threshold (โฅ75% cells 2+/3+) identifies the zolbetuximab-eligible population. Critical for HER2-negative patients who are the primary zolbetuximab target.
- 3
MSI / MMR Testing
MSI-H or dMMR gastric cancer (IHC for MLH1, MSH2, MSH6, PMS2 or PCR-based MSI) identifies the subgroup eligible for PD-1 inhibitor monotherapy in first-line. Also prognostically relevant.
- 4
PD-L1 CPS Scoring
PD-L1 CPS โฅ5 (22C3 antibody pharmDx assay) identifies the population eligible for nivolumab addition in CheckMate-649. PD-L1 should be tested concurrently with MSI and HER2.
- 5
FGFR2b Expression
FGFR2b IHC or ISH testing identifies the population potentially eligible for bemarituzumab in the context of clinical trials. This test is not yet standard outside a trial setting but is increasingly available at academic centres.
- 6
NGS-Based Comprehensive Profiling
Comprehensive genomic profiling (CGP) by NGS identifies additional actionable mutations โ KRAS G12C (sotorasib-eligible), PIK3CA, RNF43, RHOA, and CDH1 โ that may affect trial eligibility and emerging targeted therapy access.
Gastric Cancer Targeted Therapy โ Key Numbers
The most important quantitative references in gastric cancer targeted therapy.
- 4+Currently actionable biomarkers in standard advanced gastric cancer careHER2, CLDN18.2, PD-L1/MSI, and VEGFR2 โ all with approved agents โ represent a molecular precision medicine landscape unrecognised a decade ago.
- ~63%Proportion of advanced gastric cancer patients with at least one actionable biomarkerThe majority of advanced gastric cancer patients have at least one biomarker-defined treatment option โ making complete testing at diagnosis essential.
- 2024Year of NMPA approval for zolbetuximab โ the most recent approved targeted agentChina's NMPA was among the first regulators to approve zolbetuximab โ giving Chinese patients and international patients in China early access.
More from the Gastric Cancer Resource Library
Explore individual biomarker and treatment guides โ from HER2 and CLDN18.2 to immunotherapy and clinical trials.
Frequently Asked Questions: Targeted Therapy for Gastric Cancer
Do I need all biomarker tests even if my oncologist only ordered HER2?
Yes โ incomplete biomarker testing risks missing the most effective treatment for your case. If only HER2 was tested at diagnosis, you may be missing CLDN18.2 positivity (eligible for zolbetuximab), MSI-H status (eligible for pembrolizumab monotherapy), or PD-L1 CPS โฅ5 (eligible for nivolumab addition). These are not optional refinements โ they are treatment-determining tests that should be performed on every patient with newly diagnosed advanced gastric cancer. CancerFax identifies gaps in your biomarker panel and advises on supplementary testing on archival tissue or repeat biopsy.
What if my tumour is positive for both CLDN18.2 and HER2?
Co-positivity for CLDN18.2 and HER2 (approximately 8โ10% of gastric cancers) presents a treatment dilemma. Zolbetuximab's approved indication specifically excludes HER2-positive patients โ so the current standard for co-positive patients is trastuzumab-based first-line treatment. The question of whether co-positive patients might benefit from combination trastuzumab + zolbetuximab is under active clinical investigation. CancerFax can identify specific trials designed for CLDN18.2+/HER2+ co-positive patients at Chinese centres.
Are there targeted therapies for gastric cancer that are available in China but not in my country?
Yes โ several agents are available in China before other markets: zolbetuximab (NMPA approved 2024, ahead of many Western markets), RC48/disitamab vedotin (NMPA approved, developed in China), and Chinese domestic PD-1 inhibitors (sintilimab, camrelizumab) at substantially lower cost than Western originator agents. Additionally, Chinese clinical trials provide access to bemarituzumab, novel bispecific antibodies, and CLDN18.2-directed CAR-T therapy (CT-041) not yet available elsewhere. CancerFax identifies which of these options is most relevant to your specific biomarker profile.
How CancerFax Helps
CancerFax is a specialist cancer access and patient-navigation platform. We help patients and families understand their options, organise medical records, coordinate hospital communication, and support cross-border treatment planning where appropriate.
We help collect and organise reports, scans, pathology, biomarker results, and treatment history for structured case review.
We communicate with hospitals or trial teams to assess whether a case may be suitable for further screening.
We support appointment coordination, document submission, translation, and direct communication with international departments.
For international patients, we help with practical coordination โ travel planning, hospital admission guidance, and local support.
If this option is not suitable, we help explore other relevant treatments, clinical trials, or advanced care pathways.
From inquiry through to follow-up, our coordinators provide a single point of contact for the family.
CancerFax does not guarantee treatment access, eligibility, or clinical outcome. Our role is to help patients access accurate information, structured review, and appropriate specialist pathways.
Has Your Gastric Cancer Had a Complete Biomarker Panel?
CancerFax reviews your existing biomarker results and identifies whether the full panel has been tested โ recommending additional testing where needed โ then coordinates targeted therapy access at specialist centres in China.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified oncologist before making treatment decisions.