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Table 3 Currently available clinical outcomes of B7-H3 targeting immunotherapies

From: Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

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

[196,197,198]

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]