Table 1.

Selected clinical trials for antibody-based therapies targeting tumor cells, including CSCs.

Specificity/Generic Name	Description	Tumor Entity Tested	Clinical Trials/Approvals	References
CD44v6/Bivatuzumab (BIWA 4)	mAb against CD44v6, (186)Re-labeled	Inoperable recurrent and/or metastatic HNSCC, NSCLC, breast cancer	Phase I: NCT02204059, NCT02204046, NCT02254018 Outcome: Antitumor effects and effective tumor targeting was observed. Administration is well tolerated.	[148,149]
CD44v6/Bivatuzumab—mertansine	mAb against CD44v6, conjugated mertansine	Incurable HNSCC or esophagus squamous cell carcinoma (ESCC), recurrent or metastatic breast cancer	Phase I: NCT02254044, NCT02254031, NCT02254005, NCT02254018 Outcome: one fatal drug-related adverse skin event had occurred. Further clinical development was discontinued.	[87,150,151,152]
CD44v6/RG7356	mAb against CD44v6	Advanced CD44-expressing solid malignancies.	Phase I study: NCT01358903 Outcome: acceptable safety profile, modest clinical efficacy was observed. The study was terminated due to the absence of a clinical and pharmacodynamic dose-response relationship	[88]
CD44v6/RG7356	mAb against CD44v6	AML	Phase I study; NCT01641250 Outcome: the treatment was generally safe and well tolerated. Out of 44 patients, two patients achieved complete or partial response and one patient had stable disease.	[89]
CD123/JNJ-56022473 /Talacotuzumab	7G3 mAb against CD123	Elderly high-risk MDS or AML failing hypomethylating agents	Phase II: NCT02992860 Talacotuzumab as a single agent; Outcome: limited clinical efficacy and significant toxicity	[153]
CD123/JNJ-56022473 /Talacotuzumab	7G3 mAb against CD123	CD123-positive AML	Phase II/III study: NCT02472145 Talacotuzumab in combination with decitabine versus decitabine alone; Outcome: no improvement in efficacy versus decitabine alone	[107]
CD123/IMGN632	mAb G4723A against CD123 conjugated with DNA-alkylating payload of the IGN cytotoxic compounds	CD123-positive AML	Phase Ib/II study; NCT03386513 IMGN632 is given as monotherapy or in combination with AZA and/or VEN; Outcome: manageable toxicity profile; high ORR (of 75%) and CCR (of 40%) in high intensity cohort; ORR/CCR rates were even higher in the cohort of VEN-naïve patients (100%/60%, respectively)	[110,154]
CD47 IBI188/Letaplimab	mAb against CD47	Newly diagnosed higher risk MDS	Phase I study: NCT04485065 The preliminary results suggest that IBI188 in combination with AZA showed a promising efficacy and a manageable toxicity profile	[99]
CD123 and CD3 Flotetuzumab/ MGD006	bsAB (CD3ε × CD123)	Relapsed/refractory AML	Phase I/II study: NCT02152956 Outcome: acceptable safety profile, encouraging anti-leukemic activity (the complete remission rate (CRR)/CRR with partial hematological recovery was 26.7%; an overall response rate was 30.0%	[118]
CD47 and PD-1 HX009	bsAB antibody binding CD47 and PD-1	Relapsed or refractory lymphoma	Phase I/II study: NCT0409776, The preliminary results suggest that HX009 is well-tolerated and showed strong antitumor activity	[120,121]
EGFR and c-MET Amivantamab/Rybrevant/ JNJ-61186372	bsAB antibody binding EGFR with one Fab and c-Met with the other Fab	Advanced or metastatic solid tumors including EGFR-mutated NSCLC	Amivantamab was approved by the US FDA for the treatment of patients with advanced or metastatic NSCLC with EGFR ex20ins mutations, whose disease has progressed on or after platinum-based chemotherapy.	[125,126,127]
EpCAM and CD3 Catumaxomab/Removab	EpCAM × CD3; trAb binding tumor cells, T cells, and accessory cells (e.g., macrophages, DC, and NK cells through its intact Fc region	Malignant ascites derived from epithelial tumors	Catumaxomab was approved in the European Union in April 2009 for the treatment of malignant ascites, but was withdrawn in 2017 for commercial reasons.	[112]