PD-1/VEGF Bispecific Antibodies in NSCLC — PatSnap Eureka
PD-1/VEGF Bispecific Antibodies in EGFR-Mutant NSCLC
Ivonescimab and a wave of competing bispecific strategies are reshaping the patent and clinical landscape for EGFR-mutant non-small cell lung cancer — a population where both checkpoint monotherapy and anti-VEGF monotherapy have historically shown limited efficacy.
Why EGFR-Mutant NSCLC Remains a High-Unmet-Need Population
EGFR-mutant non-small cell lung cancer represents a therapeutically challenging population. EGFR TKI monotherapies — including erlotinib, gefitinib, icotinib, afatinib, osimertinib, and almonertinib — achieve median PFS of 10–19 months, but virtually all patients eventually progress. In patients without secondary T790M resistance mutations, post-TKI treatment options are largely limited to platinum-based chemotherapy with median PFS of only 4–5 months.
Anti-PD-1 monotherapy has shown poor efficacy in EGFR-mutant disease specifically — a pattern reinforced by data cited in a Regeneron Pharmaceuticals filing, which references published evidence that MET-driven NSCLC patients derive limited benefit from anti-PD-L1 monotherapy even at high tumor mutational burden. This immunosuppressive tumor microenvironment is driven by both the PD-1/PD-L1 checkpoint axis and VEGF-mediated angiogenesis — the two axes that bispecific antibodies like ivonescimab are designed to co-target in a single molecule.
The central molecular targets identified across retrieved patent results include PD-1/PD-L1, VEGF/VEGFA/VEGFR-2, EGFR (including exon 19 deletions, L858R, T790M, and exon 20 insertions), c-Met as a bypass resistance receptor, and TGF-β/TGF-βRII as an immunosuppressive cytokine. Researchers using PatSnap's IP analytics platform can map how each of these targets is claimed across competing patent families.
Six Distinct Bispecific and Combination Clusters in the Pipeline
Retrieved patent results identify six converging modality clusters addressing different arms of TKI resistance and immune exclusion in EGFR-mutant NSCLC.
PD-1 × VEGF/VEGFA Bispecific Antibodies
Ivonescimab (Akeso Biopharma) simultaneously blocks VEGF-mediated angiogenesis and PD-1-mediated immune suppression in a single molecule. The WO filing covers advanced NSCLC, perioperative settings, HNSCC, colorectal cancer, and triple-negative breast cancer. BioNTech's 2025 WO filings enter the same space with a PD-L1-arm (not PD-1) design combined with chemotherapy and CPS ≥1 patient selection — a distinct IP claim space.
Akeso · BioNTech · WO filingsBispecific EGFR/c-Met ± PD-(L)1 Inhibitors
Janssen Biotech's amivantamab (JNJ-372) patent family spans IL, EP, WO, CA, CN jurisdictions (2015–2025). Key mutations covered include L858R, T790M, exon 19 deletions, and exon 20 insertions. The bispecific format provides synergistic inhibition (14- to over 800-fold by assay) vs. monospecific mixtures. PD-(L)1 axis addition is framed as enabling ADCC and trogocytosis-based immune effector killing.
Janssen Biotech · IL/EP/WO/CA/CNAnti-PD-L1 / TGF-β Bifunctional Fusion Proteins
Merck Patent GmbH's anti-PD-L1/TGFβ Trap (bintrafusp alfa) is represented across KR, IL, JP, CN filings (2021) for stage III unresectable NSCLC in treatment-naive patients, with explicit mention of EGFR-sensitizing mutation subgroups. Doses of approximately 1200–2400 mg are claimed. Jiangsu Hengrui (CN, 2022) separately claims a PD-L1 antibody fused to a TGF-βRII extracellular domain for EGFR-mutant NSCLC specifically.
Merck Patent GmbH · Jiangsu HengruiSeparate PD-1 Antagonist + VEGFR Inhibitor Combinations
Genentech (CN, MX, KR, BR, 2021–2022) discloses treatment of PD-1/PD-L1 inhibitor-refractory cancers using VEGF signaling inhibitor combination, arguing that VEGF pathway co-inhibition can overcome checkpoint resistance. Pfizer's patent family (MX, ES, CN, TW, 2016–2019) covers PD-1 antagonist + VEGFR inhibitor combinations for PD-L1-expressing cancers — the pharmacological rationale that predates true bispecific formats.
Genentech · Pfizer · 2016–2022PD-1 / LAG-3 Bispecific Antibodies in NSCLC
F. Hoffmann-La Roche's WO filing (2024) covers a PD-1-LAG-3 bispecific in NSCLC with carboplatin/paclitaxel or carboplatin/pemetrexed. Incyte's US/WO filings (2024) cover a PD-1/LAG-3 bispecific for advanced malignancies. Bristol Myers Squibb files on LAG-3 antagonist + anti-PD-1 combinations (CN, 2023) and PD-1 + CCRT + LAG-3 maintenance (CN, 2025) — indicating expansion beyond PD-1 × VEGF into dual checkpoint blockade.
Roche · Incyte · BMS · 2023–2025EGFR TKI + CDK4/6 Inhibitor Combinations
Novartis AG discloses (multiple IL jurisdictions, 2020) a third-generation EGFR TKI + CDK4/6 inhibitor combination for EGFR-mutant NSCLC — a non-immunotherapy approach addressing TKI resistance via cell cycle pathway inhibition. Evidence is patent-only; development stage appears preclinical to early clinical. This modality is distinct from the PD-1/VEGF format but addresses the same post-TKI resistance problem via a different mechanism.
Novartis AG · IL · 2020Clinical and Pipeline Signals from Patent Analysis
Key quantitative signals extracted from patent claim language and clinical context across the retrieved dataset.
Amivantamab Combination PFS Rates — Treatment-Naive EGFR+ NSCLC
PFS rates at multiple time points from Janssen Biotech CA filing (2025), with median DOR of at least 25 months, consistent with clinical-stage data.
Therapeutic Modality Clusters by Patent Filing Activity
Relative patent filing representation across six modality clusters in the retrieved dataset, reflecting innovation intensity per approach.
Key Patent Assignees and Their Strategic Positions
Innovation activity in this dataset is predominantly patent-driven. The table below maps leading assignees to their filing geography, modality focus, and strategic signal.
Monitor Competitor Patent Activity in Real Time
Set alerts for new filings from Akeso, Janssen, BioNTech, and other key assignees via PatSnap Eureka.
What the Patent Landscape Signals for Drug Developers and IP Teams
Four high-priority strategic signals derived from the retrieved patent dataset for R&D strategy, competitive intelligence, and freedom-to-operate analysis.
Ivonescimab Holds First-Mover IP Position
Akeso Biopharma's WO filing covers a broad landscape of indications, combination partners, and disease stages for the anti-VEGF × anti-PD-1 bispecific format (PD-1 arm specifically). Competitors entering this space — notably BioNTech with anti-PD-L1/VEGF-A — are differentiating by targeting PD-L1 rather than PD-1, potentially circumventing Akeso's structural IP while claiming distinct combination regimen patents.
EGFR-Mutant NSCLC Is a Three-Bispecific Convergence Point
At least three distinct bispecific antibody classes converge on EGFR-mutant NSCLC in this dataset: PD-1/VEGF (ivonescimab), EGFR/c-Met (amivantamab), and PD-L1/TGF-β (bintrafusp alfa analogs). Each addresses a different arm of TKI resistance and immune exclusion. Combination strategies incorporating more than one bispecific represent a plausible but scientifically complex next frontier.
Clinical PFS Data Embedded in Method-of-Treatment Claims
The Janssen Biotech EGFR/c-Met + PD-(L)1 + TKI combination data — with PFS rates embedded in claim language (87% at 6 months, declining to 41% at 30 months in treatment-naive patients) — signals that clinical-stage data are being translated into enforceable method-of-treatment claims. Drug developers and IP teams should monitor these for freedom-to-operate implications.
Chinese Biopharma Filing WO Extensions Signals Global Strategy
Chinese biopharma assignees — Akeso, Jiangsu Hengrui, Shanghai Junshi, TJ Biopharma — are filing primarily in CN jurisdiction with WO extensions, indicating both domestic market protection and international patent strategy. The Jiangsu Hengrui PD-L1/TGF-βRII fusion protein for EGFR-mutant NSCLC specifically is a differentiated asset in the Chinese IP landscape that may compete with or complement ivonescimab clinically.
Translational Signals from Patent Claim Language
Among retrieved results, the most concrete clinical translation signals come from Janssen Biotech's amivantamab filings. A CA filing (2025) for treatment-naive patients provides specific PFS rates at multiple time points — 87% at 6 months, 73% at 12 months, 60% at 18 months, 48% at 24 months, and 41% at 30 months — with median DOR of at least 25 months. This language is consistent with data derived from completed or ongoing clinical studies embedded directly into enforceable method-of-treatment claims.
Merck Patent GmbH's TGF-β filings reference specific dose levels — 1200 mg Q2W, 1800 mg Q3W, 2400 mg Q3W — for the anti-PD-L1/TGFβ Trap in stage III NSCLC patients including those with EGFR-sensitizing mutations, signaling IND-enabling or clinical-stage dosing decisions. The ClinicalTrials.gov registry and EMA databases provide complementary clinical context for these patent signals.
For ivonescimab specifically, the Akeso WO filing's claim breadth across perioperative, advanced, and combination settings is consistent with a molecule that has progressed beyond pure preclinical development. However, no trial-level efficacy data — such as PFS or ORR — are explicitly stated within the retrieved patent text. PatSnap's life sciences intelligence platform links patent claims to clinical trial registrations for a complete development picture.
No retrieved results contain explicit Phase 3 trial outcome data, regulatory submission language, or approved product labeling for PD-1/VEGF bispecifics in EGFR-mutant NSCLC specifically. Researchers should use PatSnap Eureka alongside WHO clinical trial databases for a comprehensive regulatory picture.
PD-1/VEGF Bispecific Antibodies in NSCLC — key questions answered
Ivonescimab is an anti-VEGFA × anti-PD-1 bispecific antibody developed by Akeso Biopharma. It simultaneously blocks VEGF-mediated angiogenesis and PD-1-mediated immune suppression through a single molecule. The WO filing describes ivonescimab in combination with ligufalimab (anti-CD47) and in combination with chemotherapy across NSCLC, head and neck squamous cell carcinoma, colorectal cancer, and triple-negative breast cancer.
EGFR TKI monotherapies achieve median PFS of 10–19 months, but virtually all patients eventually progress. In patients without secondary T790M resistance mutations, post-TKI treatment options are largely limited to platinum-based chemotherapy with median PFS of only 4–5 months. Anti-PD-1 monotherapy has shown poor efficacy in EGFR-mutant disease specifically.
BioNTech's 2025 WO filings claim a bispecific antibody binding PD-L1 and VEGF (or the VEGF/VEGFR axis) in combination with chemotherapy for cancer treatment, with patient selection based on a combined positive score (CPS) ≥1 for PD-L1 expression. This is a distinct molecular design from ivonescimab — it uses a PD-L1 arm rather than a PD-1 arm, and targets VEGF-A broadly rather than VEGFA specifically — potentially circumventing Akeso's structural IP while claiming distinct combination regimen patents.
A Janssen Biotech CA filing (2025) for treatment-naive EGFR-positive NSCLC provides specific PFS rates at multiple time points: 87% at 6 months, 73% at 12 months, 60% at 18 months, 48% at 24 months, and 41% at 30 months, with median DOR of at least 25 months — language consistent with data derived from completed or ongoing clinical studies.
Shanghai Junshi Biosciences (CN, 2025) and TJ Biopharma (JP, 2025) independently filed on CD73 expression as a predictive biomarker for response to CD73 antagonist + PD-1/PD-L1 combination therapy in NSCLC, indicating that CD73-mediated purinergic immune suppression is an emerging resistance axis in checkpoint-treated NSCLC populations.
Chinese biopharma assignees — Akeso Biopharma, Jiangsu Hengrui Pharmaceutical, Shanghai Junshi Biosciences, and TJ Biopharma — are filing primarily in CN jurisdiction with WO extensions, indicating both domestic market protection and international patent strategy. Jiangsu Hengrui's PD-L1/TGF-βRII fusion protein for EGFR-mutant NSCLC specifically is a differentiated asset in the Chinese IP landscape.
Still have questions? Let PatSnap Eureka search the patent literature for you.
Ask PatSnap Eureka About This PipelineAccelerate Your Bispecific Antibody Intelligence
Join 18,000+ innovators already using PatSnap Eureka to map competitive IP, track clinical signals, and identify freedom-to-operate risks in oncology pipelines.
References
- Antibody that binds VEGFA and PD-1 and uses thereof to treat cancers — Akeso Biopharma Co., Ltd., 2026, WO [Patent]
- Combination therapy comprising a bispecific anti-VEGF-A and anti-PD-L1 antibody and a chemotherapy for cancer treatment — BioNTech SE, 2025, WO [Patent]
- Combination therapy comprising a PD-1/PD-L1 and VEGF/VEGFR binding agent and a chemotherapy for cancer treatment — BioNTech SE, 2025, WO [Patent]
- Method and medicament for treating cancer unresponsive to PD-1/PD-L1 signaling inhibitor — Genentech, Inc., 2021, MX [Patent]
- Methods and agents for treating cancers that do not respond to PD-1/PD-L1 signaling inhibitors — Genentech, Inc., 2021, KR [Patent]
- Method for treating cancer unresponsive to PD-1/PD-L1 signaling inhibitor — Chinese filing — Genentech, Inc., 2022, CN [Patent]
- Combination of a PD-1 antagonist and a VEGFR inhibitor for treating cancer — Pfizer Inc., 2016, MX [Patent]
- Combined therapy of PD-1 antagonist and VEGFR-2 antagonist for treating cancer patients — Pharmaceutical Antibody Company (药物抗体公司), 2023, CN [Patent]
- Combination therapies with bispecific anti-EGFR/c-Met antibodies and anti-PD-1 antibodies — Janssen Biotech, Inc., 2024, WO [Patent]
- Use of TGF-β receptor-containing fusion protein in the preparation of drugs for treating non-small cell lung cancer — Jiangsu Hengrui Pharmaceutical Co., Ltd., 2022, CN [Patent]
- Use of antibody/TGF-β protein for treatment of NSCLC — Merck Patent GmbH, 2021, IL [Patent]
- Application of a pharmaceutical composition containing an anti-PD-1 antibody in preparing drugs for treating advanced non-small cell lung cancer — Jiang Tao, 2022, CN [Patent]
- Therapeutic combination of a third generation EGFR tyrosine kinase inhibitor and a cyclin D kinase inhibitor — Novartis AG, 2020, IL [Patent]
- National Cancer Institute — Non-Small Cell Lung Cancer Treatment (PDQ) — cancer.gov
- ClinicalTrials.gov — NSCLC Bispecific Antibody Trials Registry — clinicaltrials.gov
- World Health Organization — International Clinical Trials Registry Platform — who.int
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. This report represents a snapshot of innovation signals within the retrieved dataset only and should not be interpreted as a comprehensive view of the full field, clinical pipeline, or regulatory landscape.
PatSnap Eureka searches patents and research to answer instantly.