This competitive landscape analysis was generated using AI-powered research workflows in Eureka LS, which integrates patent data, literature, and molecular insights into a structured report in minutes.

1. Target Overview

c-Met (MET proto-oncogene, receptor tyrosine kinase; UniProt P08581; HGNC 7029) is a receptor tyrosine kinase that, upon binding its ligand hepatocyte growth factor (HGF), triggers downstream RAS-ERK, PI3K-AKT, and PLCγ-PKC cascades. These pathways drive proliferation, survival, invasion, angiogenesis, and epithelial-to-mesenchymal transition (EMT). In cancer, MET is aberrantly activated through:

• Exon 14 skipping mutations (METex14) — loss of the juxtamembrane domain, preventing receptor degradation
• Gene amplification (METamp) — high-level copy number gain
• Protein overexpression — ligand-dependent or -independent activation
• Fusion events (e.g., TPR-MET) — constitutive activation

The database records 374 drugs associated with c-Met, of which 263 are in active development across 462 disease associations, underscoring its breadth as a therapeutic target.

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Traditionally, compiling this level of analysis would require weeks of manual research across platforms like Google Patents and PubMed. With Eureka LS, the same process can be automated—from extracting molecules to mapping competitive pipelines—into a structured output like the report below.

2. Approved Agents — The Commercial Baseline

Seven c-Met-targeting agents have reached regulatory approval, spanning three modality classes:

2.1 Selective MET Small Molecule Inhibitors (Type Ib)

Drug	Originator / Marketer	First Approval	Primary Indication
Tepotinib (Tepkinly®)	Merck KGaA	Mar 2020 (Japan) / Feb 2021 (US)	METex14 NSCLC
Capmatinib (Tabrecta®)	Incyte / Novartis	May 2020 (US)	METex14 NSCLC
Savolitinib (Orpathys®)	Hutchmed / AstraZeneca	Jun 2021 (China)	METex14 NSCLC; EGFR-mut MET+ NSCLC (combo)
Glumetinib	SIMM / CSPC	Mar 2023 (China)	c-Met+ NSCLC
Vebreltinib	Zhejiang Crownmab / Apollomics	Nov 2023 (China)	METamp NSCLC
Envonalkib	—	Jun 2024 (China)	NSCLC (ALK/MET)

Key competitive dynamics among selective inhibitors:

• Tepotinib and Capmatinib are the two globally approved agents for METex14 NSCLC in the US/EU; both show ~45–50% ORR in treatment-naive patients and ~40% in previously treated patients.
• Savolitinib has carved a strong China niche and is AstraZeneca’s partner for the osimertinib combination strategy.
• Glumetinib and Vebreltinib are China-only approvals competing in the METamp and c-Met overexpression space.

2.2 Multi-target Kinase Inhibitors

Drug	Originator	First Approval	Primary Indication
Crizotinib (Xalkori®)	Pfizer	Aug 2011	ALK/ROS1/MET NSCLC
Cabozantinib (Cabometyx®)	Exelixis	Nov 2012	RCC, HCC, DTC
Ensartinib	Xcovery / BeiDa	Nov 2020 (China)	ALK NSCLC

2.3 Bispecific Antibody

Drug	Originator	First Approval	Primary Indication
Amivantamab (Rybrevant®)	Janssen / Genmab	May 2021 (US)	EGFR exon 20 ins NSCLC; EGFR-mut NSCLC (1L + chemo or + lazertinib)
Amivantamab SC/Hyaluronidase	Janssen	Dec 2025	Subcutaneous formulation

Amivantamab (EGFR × c-Met bispecific) is the most commercially advanced bispecific in this space, with multiple Phase 3 approvals and active expansion into colorectal cancer (OrigAMI-2/3 trials).

2.4 ADC — Newest Approval

Drug	Originator	First Approval	Primary Indication
Telisotuzumab vedotin (Emrelis®)	AbbVie	May 2025 (US)	c-Met overexpressing non-squamous NSCLC (post-platinum)

Telisotuzumab vedotin (anti-c-Met × MMAE ADC) is the first c-Met-targeted ADC approved, representing a major modality shift in the field. It targets c-Met protein overexpression (not mutation-driven), expanding the addressable patient population.

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3. Late-Stage Pipeline — The Competitive Frontier

3.1 NDA/BLA Stage (Pending Approval)

Drug	Company	Modality	Key Indication	Notes
Dalmelitinib	Jiangsu Hansoh	Selective MET TKI	EGFR-mut MET+ NSCLC	China NDA filed; osimertinib combo
Zanzalintinib	Exelixis + Merck	Multi-kinase (AXL/MerTK/TYRO3/VEGFR/MET)	RCC, CRC, HNSCC	NDA filed; Merck collaboration for pembrolizumab combos

3.2 Phase 3

Drug	Company	Modality	Key Indication
Telisotuzumab adizutecan	AbbVie	ADC (c-Met × Top I)	EGFR+ non-sq NSCLC, CRC, pancreatic
Sitravatinib	BeiGene / Mirati	Multi-kinase (AXL/RET/VEGFR/MET)	Advanced NSCLC (combo w/ nivolumab)
Vilzemetkib	Advenchen / Chia Tai Tianqing	Selective MET TKI	Advanced NSCLC, thyroid

Telisotuzumab adizutecan (AbbVie’s second-generation c-Met ADC with a topoisomerase I payload) is the most strategically important Phase 3 asset, being evaluated in 26 disease indications — a broad-spectrum ADC approach.

3.3 Phase 2 Highlights

Drug	Company	Modality	Notable Data
SKB-571	Kelun Botai / Merck & Co.	EGFR × c-Met ADC	Phase 2; GI cancers (gastric, CRC, esophageal)
Pamvatamig	—	Bispecific antibody	Phase 2
Davutamig	Regeneron	Bispecific antibody	Phase 1/2; c-Met+ NSCLC
Emibetuzumab	Eli Lilly	Monoclonal antibody	Phase 2
Vabametkib	—	Selective MET TKI	Phase 2

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4. Key Clinical Evidence

4.1 METex14 Skipping NSCLC — Established Standard of Care

Tepotinib (VISION trial, ≥3-year follow-up): 313 patients enrolled; 15.7% discontinued due to treatment-related adverse events. Long-term durability confirmed as a first-line standard.

Savolitinib (Phase 3b confirmatory, China): In 166 Chinese patients with METex14-mutated NSCLC:

• Treatment-naive cohort: ORR = 62% (95% CI: 51–72%)
• Previously treated cohort: ORR = 42% (95% CI: 31–53%)

4.2 EGFR-mutant MET-amplified NSCLC — Combination Strategy

Savolitinib + Osimertinib (SACHI Phase 3 interim, China): In 211 patients with EGFR-mut MET-amplified NSCLC progressing on prior EGFR-TKI:

• Savolitinib + osimertinib vs. chemotherapy: mPFS HR = 0.40 (95% CI: 0.28–0.59; p<0.0001)
• mPFS: 6.9 months vs. 3.0 months
  This combination is a pivotal data point establishing the EGFR + MET dual blockade paradigm.

4.3 MET Amplification NSCLC — Vebreltinib (KUNPENG Phase 2)

In 86 patients with METamp-driven NSCLC:

• High-level amplification subgroup: ORR = 75.0%
• Overall: ORR = 48.8% (95% CI: 38.3–59.4%)

4.4 Amivantamab Expansion

Beyond NSCLC, amivantamab is demonstrating activity in colorectal cancer:

• OrigAMI-2 (Phase 3): amivantamab + FOLFOX/FOLFIRI vs. cetuximab in 1L RAS/BRAF-wt mCRC — positive readout
• OrigAMI-3 (Phase 3): amivantamab + FOLFIRI in 2L+ mCRC — positive readout

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5. Competitive Analysis by Modality

5.1 Selective MET TKIs — Crowded but Differentiated

The selective TKI class is the most mature. Competition is primarily on selectivity, CNS penetration, and resistance profile:

• Tepotinib & Capmatinib: global standard of care in METex14 NSCLC; head-to-head data lacking, but real-world data shows comparable efficacy
• Savolitinib: AstraZeneca partnership gives it the strongest combination strategy pipeline; SACHI Phase 3 data makes it the leader in EGFR+MET combination
• China-origin TKIs (Glumetinib, Vebreltinib, Dalmelitinib): compete primarily in the Chinese market; Vebreltinib’s KUNPENG data is particularly strong for METamp

Key unmet need: resistance to selective MET TKIs (secondary MET mutations, bypass activation via KRAS, EGFR, HER3) drives the rationale for next-generation agents and combinations.

5.2 ADCs — The Emerging Dominant Modality

The c-Met ADC space is the most active frontier:

Drug	Payload	Stage	Strategic Angle
Telisotuzumab vedotin	MMAE (tubulin)	Approved (2025)	c-Met overexpression; broad NSCLC pop.
Telisotuzumab adizutecan	Exatecan (Top I)	Phase 3	Next-gen payload; 26 indications
SKB-571 (Kelun/Merck)	—	Phase 2	EGFR × c-Met bispecific ADC; GI focus
SHR-1826, RC-108, SKB-571, TQB6411	Various	Phase 1/2	Chinese ADC wave

The shift from MMAE to topoisomerase I payloads (exatecan/DXd class) in second-generation c-Met ADCs mirrors the broader ADC field trend, with potentially improved bystander killing and activity in low-antigen-expressing tumors.

5.3 Bispecific Antibodies — EGFR × c-Met Dominates

Drug	Targets	Stage	Company
Amivantamab	EGFR × c-Met	Approved	J&J
SKB-571	EGFR × c-Met	Phase 2 (ADC)	Kelun / Merck
PM-1080	—	Phase 3	—
Bafisontamab	—	Phase 2	—
Davutamig	c-Met	Phase 1/2	Regeneron
TQB2922, SHR-9839	—	Phase 2	Chinese biotechs
GB-263	Trispecific	Phase 2	—

EGFR × c-Met bispecifics address a critical clinical problem: MET amplification as the primary acquired resistance mechanism to EGFR TKIs (~20–25% of osimertinib-resistant cases). Amivantamab’s success has validated this concept and triggered a wave of follow-ons.

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6. Deal Intelligence & BD Activity (2022–2026)

Recent notable deals confirm strong investor and pharma interest:

Deal	Date	Value	Significance
EGFR/c-MET nano-bispecific ADC licensing	Aug 2025	$15M upfront + $1.15B milestones	High-value Chinese ADC out-licensing
Exelixis + Merck (Zanzalintinib + pembrolizumab/belzutifan)	Oct 2024	Undisclosed	Validates multi-kinase MET inhibitor combos with I-O
Apollomics + LaunXP (Vebreltinib)	Mar 2025	$10M upfront + $50M milestones	US/global commercialization of China-origin TKI
Roche + Merck KGaA China lung cancer collaboration	Mar 2025	Undisclosed	Co-promotion of tepotinib in China
Samsung Bioepis + Phrontline (c-Met ADC partnership)	Oct 2025	Undisclosed	ADC manufacturing/development partnership

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7. Key Players Summary

Company	Key Assets	Strategic Position
J&J (Janssen)	Amivantamab (IV + SC), Lazertinib combo	Dominant in EGFR × c-Met bispecific; expanding to CRC
AbbVie	Telisotuzumab vedotin (approved), Telisotuzumab adizutecan (Ph3)	ADC leader; first-to-market c-Met ADC; broadest ADC pipeline
Novartis	Capmatinib	Global METex14 standard of care
Merck KGaA	Tepotinib	Global METex14 standard of care; China collaboration with Roche
AstraZeneca / Hutchmed	Savolitinib	Strongest combo strategy (SACHI data); China leadership
Exelixis + Merck & Co.	Zanzalintinib (NDA)	Next-gen multi-kinase; broad oncology
Jiangsu Hansoh	Dalmelitinib (NDA)	China-origin selective TKI; combo strategy
Apollomics / Crownmab	Vebreltinib	METamp-focused; strong KUNPENG data
Kelun Botai / Merck & Co.	SKB-571	EGFR × c-Met ADC; GI expansion
Regeneron	Davutamig	Early-stage bispecific entrant

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8. Competitive Dynamics & Strategic Outlook

1. Biomarker stratification is the key battleground. The field has fragmented into three distinct patient populations: METex14 (TKIs), METamp (TKIs + combos), and c-Met overexpression (ADCs). Each requires different diagnostic approaches and drug strategies.

2. ADCs are displacing TKIs in overexpression-driven disease. Telisotuzumab vedotin’s approval marks the beginning of an ADC era in c-Met oncology. The payload evolution (MMAE → Top I) and the pipeline density (8+ ADCs in active development) suggest ADCs will become the dominant modality for c-Met overexpressing tumors within 3–5 years.

3. Combination strategies are becoming standard. The SACHI data (savolitinib + osimertinib) and amivantamab’s combination approvals have established that dual EGFR + MET blockade is superior to monotherapy in EGFR-resistant, MET-amplified NSCLC. This will drive demand for c-Met agents as combination partners.

4. Chinese biotechs are a major competitive force. Glumetinib, Vebreltinib, Dalmelitinib, SKB-571, and multiple ADCs originate from Chinese companies. The out-licensing of the EGFR/c-MET nano-bispecific ADC at $1.15B in milestones signals that Chinese c-Met assets are increasingly competitive globally.

5. Resistance mechanisms will define next-generation development. Secondary MET mutations (D1228N, Y1230C/H) and bypass resistance via KRAS, HER3, and FGFR are active areas of research. Next-generation selective TKIs and bispecifics targeting these mechanisms represent the next wave.

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Data sourced from PatSnap Life Sciences database. Pipeline status reflects data as of May 2026. Drug counts and trial totals reflect database coverage at time of retrieval.