Table 2.
Representative bispecific and biparatopic ADCs in clinical development or approved
| Drug/Program (INN) | Target 1 | Target 2 | Payload | Linker type | DAR | Company | Indication(s) | Clinical stage/key trials | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| BL-B01D1 (izalontamab brengitecan; iza-bren) | EGFR | HER3 | Topoisomerase I inhibitor (Ed-04) | Cleavable (tetrapeptide-based) | ~8 | SystImmune/Sichuan Baili (Biokin); BMS ex-China | Solid tumors: NPC, ESCC, NSCLC, TNBC, urothelial | Approved (China, NMPA): r/m NPC (22 Jun 2026); r/m ESCC (Jul 2026) — first bsADC approved worldwide. Phase III ongoing (BL-B01D1-303 NCT06118333; -305 ESCC; -307 TNBC). FDA BTD in EGFR-mutant NSCLC | 270,271 |
| JSKN003 (anbenitamab repodatecan) — INN added | HER2 (ECD2) | HER2 (ECD4) | Topoisomerase I inhibitor | Cleavable (glycan site-specific) | ~4 | Alphamab Oncology/JMT-Bio (CSPC), China rights | HER2+ and HER2-low breast; platinum-resistant ovarian (PROC); gastric; CRC | Phase III: HER2 + BC (JSKN003-301, vs T-DM1), HER2-low BC (-302), PROC (-306). Phase II: gastric, CRC. FDA BTD + Fast Track (PROC); ODD (GC/GEJ); NMPA BTD (PROC, CRC) | 272 |
| JSKN016 | TROP2 | HER3 | Topoisomerase I inhibitor | Cleavable (glycan site-specific) | 4 | Alphamab Oncology | HER2-negative breast cancer/TNBC; lung cancer | Phase III in TNBC (JSKN016-301; first patient dosed Mar 2026). Phase I JSKN016-101 (NCT06592417) | 273 |
| TQB2102 | HER2 (ECD2) | HER2 (ECD4) | Topoisomerase I inhibitor | Cleavable (enzyme-cleavable) | 6 | Chia Tai Tianqing | HER2+ and HER2-low breast cancer (incl. neoadjuvant); HER2-expressing solid tumors | Phase III (2 L HER2 + BC vs T-DM1; HER2-low BC vs chemotherapy). Phase II neoadjuvant HER2 + BC (NCT06198751); Phase I/II NCT06115902 | 274 |
| AZD9592 (tilatamig samrotecan) | EGFR | c-MET | Camptothecin-derived topoisomerase I inhibitor (samrotecan, AZ14170132) | Cleavable (proprietary) | ~6 | AstraZeneca | NSCLC, HNSCC, colorectal cancer | Phase I/II EGRET (first-in-human), monotherapy and in combination with osimertinib | 275 |
| REGN5093-M114 | MET (epitope 1) | MET (epitope 2) | Maytansinoid M24 (as linker-payload M114) | Cleavable (protease) | ~3.2 | Regeneron | MET-overexpressing NSCLC | Phase I/II (NCT04982224), monotherapy and with cemiplimab | 276 |
| IMGN151 (opugotamig olatansine) | FRα (epitope 1) | FRα (epitope 2) | Maytansinoid (DM21) | Cleavable (stabilized peptide) | 3.5 | ImmunoGen/AbbVie | Ovarian, endometrial, cervical cancer (broad range of FRα expression) | Phase I (IMGN151-1001, first-in-human dose escalation/optimization/expansion) | 277 |
| DB-1419 | B7-H3 (CD276) | PD-L1 | Topoisomerase I inhibitor (P1003) | Cleavable (maleimide tetrapeptide) | ~8 | DualityBio | Advanced/metastatic solid tumors, including PD-L1-resistant disease | Phase I/IIa first-in-human (NCT06554795); FDA IND and Australian CTN cleared | 278 |
| M1231 | MUC1 (tumor-associated, hypoglycosylated) | EGFR | Hemiasterlin analog (SC209) | Cleavable (ValCit-PABA) | ~4 | Merck KGaA/Sutro Biopharma | Solid tumors (NSCLC, ESCC) | Phase I (NCT04695847); enrollment complete, no clinical results published — program status to be confirmed | 279 |
| ZW49 (zanidatamab zovodotin) | HER2 (ECD2) | HER2 (ECD4) | N-acyl sulfonamide auristatin (ZD02044) | Cleavable (protease) | ~2 | Zymeworks | HER2-expressing solid tumors | Phase I; clinical development formally discontinued Q2 2024 following portfolio prioritization | 280 |
| MEDI4276 | HER2 (subdomain 2) | HER2 (subdomain 4) | Tubulysin AZ13599185 (MMETA) | Cleavable (protease; maleimidocaproyl) | 4 | AstraZeneca/MedImmune | HER2+ breast and gastric cancer | Phase I; discontinued — narrow therapeutic index with dose-limiting hepatic toxicity | 281 |
BC breast cancer, bsADC bispecific antibody–drug conjugate, BTD breakthrough therapy designation, CRC colorectal cancer, CTN clinical trial notification, DAR drug-to-antibody ratio, ECD extracellular domain, ESCC esophageal squamous cell carcinoma, FRα folate receptor alpha, GC/GEJ gastric/gastro-esophageal junction, HNSCC head and neck squamous cell carcinoma, IND investigational new drug, NPC nasopharyngeal carcinoma, NSCLC non-small cell lung cancer, ODD orphan drug designation, PROC platinum-resistant ovarian cancer, r/m recurrent or metastatic, scFv single-chain variable fragment, SEED strand-exchange engineered domain, TNBC triple-negative breast cancer, T-DM1 trastuzumab emtansine