. Author manuscript; available in PMC: 2024 Oct 18.

Published in final edited form as: Nat Rev Clin Oncol. 2022 Feb 25;19(5):328–341. doi: 10.1038/s41571-022-00606-4

Table 2 │.

Predicted efficacy of novel treatment strategies against common subtypes of GIST

Treatment strategy	Novel treatment	Target	Predicted efficacy
Treatment strategy	Novel treatment	Target	KIT-mutant GIST	PDGFRA-mutant GIST	SDH-deficient GIST
TKI-based	THE-630 (NCT05160168)	KIT driver (all known primary and secondary variants)	√	x	x
	NB003 (NCT04936178) formally known as AZD3229	KIT or PDGFRA driver	√	√	x
	Bezuclastinib (previously known as CGT9486 and PLX9486) + sunitinib (NCT05208047;¹³⁴)	KIT driver	√	√	x
	TKI + MEKi (such as imatinib plus binimetinib; NCT01991379;^137,139)	KIT or PDGFRA driver	√	√	x
	TKI + PI3Ki + MEKi (¹⁴⁰)	KIT or PDGFRA driver	√	√	x
ADC	DS-6157a (NCT04276415)	GPR20	√	√	√
RLT	¹⁷⁷Lu-NeoB (NCT03872778)	GRPR (expression determined by ⁶⁸Ga-NeoB uptake)	√	?	?
DDR	Temozolomide (NCT03556384;¹⁶¹)	SDH-deficient cells (negative for MGMT expression)	x	x	√
IO	TKI + ICI (such as axitinib and avelumab; NCT04258956)	KIT or PDGFRA driver and PD-1 or PD-L1	√	√	x
IO	TKI + immunostimulant (such as IFNα¹⁶⁷)	KIT or PDGFRA driver and cytokine receptors	√	√	x

?, unknown; ADC, antibody–drug conjugate; DDR, DNA damage repair; GIST, gastrointestinal stromal tumour; GPR20, G protein-coupled receptor 20; GRPR, gastrin-releasing peptide receptor (also known as bombesin receptor subtype 2 (BB₂)); ICI, immune-checkpoint inhibitor; IO, immuno-oncology; MEKi, MEK inhibitor; PI3K, PI3K inhibitor; RLT, radioligand therapy; SDH, succinate dehydrogenase; TKI, tyrosine kinase inhibitor.