Why GC/GEJC Remains a High-Unmet-Need Indication

Gastric cancer (GC) and gastroesophageal junction cancer (GEJC) together carry a 5-year overall survival rate of approximately 20% for advanced disease — a figure that has changed little despite decades of cytotoxic chemotherapy. The therapeutic landscape is now being restructured around molecularly stratified targets, principally HER2 (ERBB2), Claudin 18.2 (CLDN18.2), and VEGFR-2 (KDR), alongside immune checkpoint co-targeting strategies. Secondary targets appearing across multiple patent filings include LAG-3, TIGIT, PD-1/PD-L1, c-Met (MET), CEACAM5, CD47/SIRPα, and CD39.

HER2 overexpression is present in approximately 15% of GC/GEJC patients, according to a Dana-Farber Cancer Institute patent framing the unmet need for additional targeted strategies. That same filing notes that trastuzumab is the only agent to have demonstrated efficacy in this HER2-positive subset — a gap that has directly motivated the development of next-generation HER2-targeted ADCs and combination regimens. Critically, CLDN18.2-positive patient populations are often HER2-negative, establishing a complementary treatment axis that does not compete with HER2 therapies for the same patients, as noted explicitly by Suzhou Transcenta Therapeutics in their 2024 WO patent filing.

According to WHO cancer statistics, gastric cancer ranks among the leading causes of cancer mortality worldwide, underscoring why this pipeline has attracted investment from major global pharma companies, Chinese biotech, and academic-industry hybrid entities alike. The patent record analysed here spans filings from 2012 to 2025, with the most recent cluster concentrated in 2024–2025 — a clear signal of accelerating development activity.

Claudin 18.2: The Most Active ADC Target in the Dataset

Claudin 18.2 generates the highest volume of ADC and combination patent filings in this dataset, and its structural biology explains why. CLDN18.2 is a 278 kDa four-transmembrane-domain tight junction protein with two extracellular loops accessible for antibody binding, selectively overexpressed in gastric mucosal tumors and absent from most normal tissues — a specificity profile that is highly desirable for ADC development where off-target toxicity is a primary concern.

The foundational IP for CLDN18.2 ADCs was established by TRON — Translational Oncology at the University Medical Center, Johannes Gutenberg University Mainz gGmbH — in WO and CA patents filed in 2016. These filings describe IMAB362-vcMMAE and IMAB362-DM4 conjugates, demonstrating in vitro killing of CLDN18.2-positive gastric and pancreatic cells and in vivo dose-dependent tumor regression in xenograft models. A mechanistically important feature documented in these TRON patents is the bystander killing effect: both DM4 and vcMMAE conjugates kill CLDN18.2-negative cells co-cultured with CLDN18.2-positive cells in vitro, which has direct relevance for heterogeneous tumors where not all cells express the target.

Downstream development has proliferated across multiple Chinese biotech and global pharma licensees. Keymed Biosciences (Chengdu) filed a 2025 WO patent covering MMAE-conjugated CLDN18.2 ADC dosing at 0.3–3.4 mg/kg, with clinical development signals. SOTIO Biotech’s 2025 WO patent describes an anthracycline derivative payload ADC combined with a PD-1/PD-L1 axis inhibitor, and explicitly references four CLDN18.2 ADCs already in Phase 1 clinical trials: RC118, SYSA-1801, ATG-022, and JS107. The mechanistic rationale offered by SOTIO — that ADCs may enhance immunotherapeutic efficacy through immunogenic cell death — represents an increasingly common rationale for ADC + checkpoint inhibitor combinations across oncology.

On the naked antibody front, zolbetuximab (IMAB362) — the same antibody backbone used in TRON’s ADC patents — is being evaluated in Phase III trials. Astellas Pharma’s EP and IL patents reference NCT03504397 (SPOTLIGHT) and NCT03653507 (GLOW), evaluating zolbetuximab combined with mFOLFOX6 or CAPOX in CLDN18.2-positive, HER2-negative locally advanced or metastatic GC/GEJC. These Phase III benchmarks are being used as comparators in newer filings: a Transcenta CN 2026 patent explicitly compares CLDN18.2 ADC combination efficacy against CheckMate 649 nivolumab + chemotherapy data in GC/GEJC patients, referencing a 2024 April 18 data cutoff.

“CLDN18.2-positive patient populations are often HER2-negative — establishing a complementary treatment axis that does not compete with HER2 therapies for the same patients.”

HER2 ADC Combinations: Beyond Trastuzumab Monotherapy

HER2-targeted ADC development in GC/GEJC is moving decisively toward combination strategies, with the most clinically advanced pairing in this dataset being RemeGen’s RC48 (disitamab vedotin) combined with toripalimab (anti-PD-1). RemeGen filed two WO patents in 2025 covering methods of treating cancer using anti-HER2 ADCs with anti-PD-1 antibodies, specifying gastric adenocarcinoma and GEJC adenocarcinoma as explicit indications — the 2025 filing date suggesting active IND-enabling or Phase I/II-stage work.

Earlier in the pipeline, Seagen’s 2019 SG patent covers tucatinib combined with trastuzumab in gastric cancer patient-derived xenograft (PDX) models, providing in vivo tumor volume reduction data in a gastric cancer model (GXA 3054). F. Hoffmann-La Roche’s 2012 CN patent on HER2 signaling modulators provides molecular stratification context for HER2/neu (ErbB2) pathway inhibition and tumor regression as key endpoints — foundational science that underpins the current generation of HER2-targeted strategies.

The strategic logic behind HER2 ADC + anti-PD-1 combinations is well-established in broader oncology: the cytotoxic payload of an ADC can induce immunogenic cell death, releasing tumor-associated antigens that prime T-cell responses, which are then amplified by checkpoint inhibition. In GC/GEJC specifically, this rationale is reinforced by the fact that HER2-positive tumors represent a biomarker-selected population where combination depth may overcome the resistance mechanisms that limit trastuzumab monotherapy. According to ASCO clinical guidance, HER2 testing is now standard in the metastatic gastric cancer workup, making biomarker-selected trial design increasingly feasible.

AbbVie represents a mechanistically distinct HER2-adjacent approach: two 2024 WO filings describe telisotuzumab — an anti-c-Met antibody — conjugated to a topoisomerase I inhibitor (Top1i) for gastroesophageal adenocarcinoma (GEA) and MET gene-amplified tumors. The use of a Top1i payload rather than the more common auristatin or maytansinoid payloads signals ongoing payload diversification in the GC/GEJC ADC space.

VEGFR-2 Combinations: Ramucirumab and Small-Molecule Approaches

Ramucirumab (anti-VEGFR-2) is the agent of record in all VEGFR-targeted filings for GC/GEJC in this dataset. MedImmune/AstraZeneca’s WO patent specifies clinical dosing for advanced GC/GEJ adenocarcinoma: ramucirumab at 8 mg/kg every two weeks (Q2W) combined with durvalumab at 750 mg Q2W — a regimen consistent with clinical trial-level administration. The same combination is covered in a 2022 JP patent from MedImmune Limited, representing multi-jurisdictional IP protection of this VEGFR-2 + PD-L1 strategy.

Merck Sharp & Dohme’s 2017 WO patent covers ramucirumab combined with pembrolizumab for advanced GC/GEJ adenocarcinoma, with full amino acid sequence specifications for both antibodies — a level of technical specificity consistent with clinical-stage IP prosecution. The multi-jurisdictional filing pattern across WO, US, JP, and CN jurisdictions indicates aggressive portfolio protection of this VEGFR-2 + PD-1 combination.

Small-molecule VEGFR inhibition is also represented. Chia Tai Tianqing Pharmaceutical Group’s 2024 US patent describes anlotinib — a multi-target receptor tyrosine kinase inhibitor with VEGFR activity — combined with anti-PD-L1 antibodies for GC/GEJ. The filing references patient populations achieving a disease control rate (DCR) of ≥80% with anlotinib + anti-PD-L1 maintenance therapy, with data from long-term follow-up. Separately, the sole academic literature result in this dataset reports a meta-analysis of clinical randomised controlled trials examining camrelizumab (anti-PD-1) combined with apatinib (a VEGFR-2 small-molecule inhibitor) in advanced gastric cancer, providing pooled evidence of clinical activity for this PD-1 + VEGFR approach in the Chinese clinical research context. As noted by EMA and FDA guidance frameworks, combination oncology regimens require robust biomarker-selection strategies to demonstrate incremental benefit over approved monotherapy standards.

Multi-Target Regimens and Emerging Combination Strategies

The gastric cancer pipeline is moving beyond doublet approaches toward multi-agent combinations designed for biomarker-selected patient sub-populations, where multi-mechanism co-targeting may overcome resistance mechanisms. Several distinct combination architectures are visible in the patent record.

CLDN18.2 ADC + PD-1/PD-L1 Inhibitors

This is the most frequently encountered emerging combination in the dataset. Filings from SOTIO Biotech, Keymed Biosciences, and Innovent Biologics all describe CLDN18.2 ADC + checkpoint inhibitor combinations, with SOTIO’s 2025 patent providing the mechanistic rationale that ADCs may enhance immunotherapeutic efficacy through immunogenic cell death. Phase 1 trial evaluation is underway for multiple agents in this combination class.

CLDN18.2 ADC + VEGFR Inhibition + Chemotherapy

Innovent Biologics’ CN 2025 filing explicitly describes a CLDN18.2 ADC combined with sintilimab (anti-PD-1), ramucirumab, or bevacizumab for first-line CLDN18.2-positive advanced GC/GEJC after failure of standard therapy — a three-agent regimen incorporating ADC cytotoxicity, VEGFR anti-angiogenic blockade, and immune checkpoint inhibition simultaneously.

Anti-TIGIT + PD-1/PD-L1 + Chemotherapy

Roche/Genentech and Merck both have active filings covering tiragolumab + atezolizumab + CAPOX/oxaliplatin for GC/GEJC. Roche specifies a fixed-dose regimen: 600 mg tiragolumab + 1200 mg atezolizumab + CAPOX Q3W, with signals suggesting this triplet is in clinical evaluation. Bristol-Myers Squibb is the highest-volume single assignee in this dataset, filing LAG-3 + PD-1 combination therapy patents (relatlimab + nivolumab ± FOLFOX/SOX/XELOX chemotherapy) across at least 8 jurisdictions — WO, US, CA, AU, BR, IN, IL, SG, MX, JP, and CN — representing aggressive IP protection of a clinical-stage program.

Bispecific Antibody Approaches

Early-stage bispecific antibody strategies are emerging from Chinese biotech (CLDN18.2 × CD47 bispecific from Baoship Biomedical Technology, CN 2023), Janssen Biotech (EGFR × c-Met), and Incyte (PD-1 × TGFβR2). The CLDN18.2 × CD47 bispecific is mechanistically notable: it leverages selective tumor targeting via CLDN18.2 to minimise on-target CD47 toxicity on normal cells — addressing a key safety concern that has limited pure CD47 blockade approaches.

Assignee Landscape and IP Strategy Implications

The assignee landscape in this dataset reveals distinct IP positioning strategies across global pharma, Chinese biotech, and academic-industry hybrid entities. Understanding these positions is essential for drug developers assessing freedom-to-operate, licensing opportunities, or partnership strategies in GC/GEJC.

Bristol-Myers Squibb is the highest-volume single assignee in the dataset by jurisdiction count, filing LAG-3 + PD-1 combination therapy patents (relatlimab + nivolumab ± FOLFOX/SOX/XELOX) across at least 8 jurisdictions including WO, US, CA, AU, BR, IN, IL, SG, MX, JP, and CN. This multi-jurisdictional filing pattern represents aggressive IP protection of a clinical-stage combination program and signals that BMS views GC/GEJC as a priority indication for this combination.

TRON (Translational Oncology at Johannes Gutenberg University Mainz) holds foundational CLDN18.2 ADC patents in WO and CA jurisdictions, covering DM4- and vcMMAE-conjugated IMAB362 (zolbetuximab backbone). These foundational patents provide the IP basis for multiple downstream licensees and development programs. Drug developers entering the CLDN18.2 ADC space should assess freedom-to-operate relative to these IMAB362-based ADC patents covering MMAE and DM4 conjugates with cleavable linkers.

Chinese biotech companies — Sichuan Kelun-Biotech, Keymed Biosciences, Innovent Biologics (Xinda Biologics), Suzhou Transcenta, and others — collectively generate a numerically significant portion of CLDN18.2 and combination IP filings in this dataset. Filing patterns are predominantly in CN jurisdiction with WO, TW, and IL extensions. According to WIPO patent statistics, China has become one of the leading jurisdictions for biopharmaceutical patent filings globally, and the GC/GEJC ADC space reflects this trend clearly. Multinational companies evaluating licensing or partnership should assess the breadth and geographic coverage of Chinese assignees’ portfolios, particularly for MMAE-payload ADCs against CLDN18.2.

MedImmune/AstraZeneca holds three retrieved patents covering ramucirumab + durvalumab for advanced GC/GEJ adenocarcinoma across WO and JP jurisdictions, representing AstraZeneca’s VEGFR-2 + PD-L1 combination IP position. Merck Sharp & Dohme covers the ramucirumab + pembrolizumab combination with full sequence specifications. New entrants focusing on VEGFR-2 combinations will need to differentiate on combination partner, patient selection biomarker, or linker/payload to navigate these established IP positions. The PatSnap Life Sciences platform provides freedom-to-operate analysis tools specifically designed for these complex multi-target combination landscapes. For deeper competitive intelligence on any of these assignees, PatSnap’s intelligence resources offer structured pipeline tracking across jurisdictions.

“The four-drug combinatorial regimens signal that the field is moving toward biomarker-selected patient sub-populations where multi-mechanism co-targeting may overcome resistance mechanisms.”