Table 3.

Currently available clinical outcomes of B7-H3 targeting immunotherapies

Agent	Agent type	Trial ID	Type of study	Cancer types	Enrollment	Study design	Main conclusion	References
MGC018	ADC	NCT03729596	Phase I/II clinical trial	HNSCC, TNBC, melanoma, NSCLC, metastatic castrate-resistant prostate cancer (mCRPC)	80	Open-label dose escalation + cohort expansion	49/80 of the enrolled pts took 3 mg/kg MGC018 as determined in dose escalation study. 87.7% encountered at least 1 adverse event, most commonly neutropenia, fatigue, palmar-plantar erythron dysesthesia and headache. PSA decline and tumor regression was observed in prostate cancer pts	[176, 177]
DS-7300	ADC	NCT04145622	Phase I/II clinical trial	11 advanced solid cancers	127	Open-label dose escalation + cohort expansion	Treatment-emergent adverse events occurred in 124/127 pts (98%); the most common were nausea (61%), infusion-related reaction (35%), and vomiting (31%). Responses were observed in 30/91 evaluable pts (33%) in total, 7/9 pts with SCLC, 2/5 with NSCLC, and 16/42 with mCRPC	[179]
MGA271	ADCC	NCT01391143	Phase I clinical trial	7 advanced solid cancers	46	Open-label single-arm	MGA271 was well tolerated, with no dose-limiting toxicity. Pts experienced disease stabilization (> 12 weeks) and tumor shrinkage (2–69%) across several tumor types	[182]
MGA271	ADCC	NCT02923180	Phase II clinical trial	Prostate cancer	32	Open-label single-arm	12% of the enrolled pts experienced grade 3/4 adverse events. Post-treatment PSA declines, PSA0 at 1-year post-op, Gleason grade group changes showed promising results. Pathologic and immunologic evaluation of prostate revealed upregulation of CD8+ T cells, PD-1/PD-L1 expression, and immune activation	[183]
MGA271 + pembrolizumab	ADCC	NCT02475213	Phase I/II clinical trial	Advanced solid tumors	133	Open-label dose escalation	116/133 pts experienced treatment-related adverse events, 38/133 ≥ grade 3. Objective response was observed in 6/18 pts with HNSCC and in 5/14 pts with NSCLC, 1/17 patients with urothelial cancer and 1/13 pts with melanoma. Pts with previous ICI treatment had a poorer prognosis	[127]
B7H3 CAR-T	CAR T cells	ChiCTR1900023435 ChiCTR2100044386	Case reports	Meningioma, glioblastoma and basal cell carcinoma	–	Case reports	CAR-T infusion was well tolerated in three cases. No obvious therapy response was observed in meningioma and glioblastoma cases. Partial response in basal cell carcinoma case	[196–198]
4-1BBζ B7H3-EGFRt-DHFR	CAR T cells	NCT04483778	Phase I clinical trial	Relapsed/ refractory non-CNS tumors in pediatric or young adult patients	16	Open-label non-randomized two arms	No dose-limiting toxicity was observed in the first infusion, maximum circulating CAR-T expansion on first infusion was 4.98 cells/μL with median persistence of 28 days. Stable disease was observed in 3 of the 9 pts infused	[199]
131I-Omburtamab	Radioimmunotherapy	NCT00089245	Phase I clinical trial	Recurrent or metastatic neuroblastoma	105	Open-label single-arm	Self-limited fever, nausea and headache, creatinine elevation, and grade 1 and 3 transient elevated serum transaminase was observed. Nearly 50% of pts survive at least 36 months. Over 50% of pts were still alive when data was last updated	[202, 203]
131I-Omburtamab	Radioimmunotherapy	–	Clinical retrospective analysis	Recurrent rhabdomyosarcoma	23	Retrospective review	A prolonged survival of pts receiving intraventricular 131I-Omburtamab (P = 0.003)	[205]
124I-Omburtamab	Radioimmunotherapy	NCT01502917	Phase I clinical trial	Diffuse intrinsic pontine glioma in children	46	Open-label dose escalation	10/46 enrolled pts experienced grade 3 adverse events considered related to the agent. A dose up to 8 mCi and infusion volume of 8 mL were found to be safe. The median survival increased 3–4 months compared to historical control data	[207, 208]