Immune approaches beyond traditional immune checkpoint inhibitors for advanced renal cell carcinoma

Figures & data

Table 1. Current active and recruiting clinical trials evaluating engineered interleukins in metastatic RCC.

Trial number	Interleukin target	Agent(s)	Setting	Primary outcome measures
NCT04540705	IL-2	Bempegaldesleukin, nivolumab, and TKI vs. nivolumab and TKI	Frontline	AEs, DLT
NCT02799095	IL-2	Nemvaleukin-alfa alone and with pembrolizumab	Refractory or intolerant to approved therapies	AEs, ORR
NCT04235777	IL-12	Bintrafusp alfa with NHS-IL-12	Refractory or intolerant to approved therapies	Safety and tolerability
NCT04234113	IL-15	Nanrilkefusp alfa alone and with pembrolizumab	Refractory or intolerant to approved therapies	AEs, DLT
NCT03228667	IL-15	N-803 with anti-PD-1/PD-L1 ICIs and PD-L1 targeting high-affinity NK cells	Refractory to prior ICI	ORR
NCT04628780	IL-15	PF-07209960	Progressed on at least 2 prior lines of therapy	AEs, DLT, ORR
NCT04374877	IL-27	SRF388	Prior treatment with VEGF-targeted therapy and ICI	AEs, DLT, ORR

TKI = tyrosine kinase inhibitor, AEs = adverse events, DLT = dose-limiting toxicities, ORR = objective response rate, ICI = immune checkpoint inhibitor, VEGF = vascular endothelial growth factor.

Table 2. Current active and recruiting clinical trials evaluating novel immune checkpoint targets involving patients with metastatic RCC.

Trial number	Immune checkpoint target(s)	Agent(s)	Setting	Primary outcome measures
NCT05805501	LAG-3 and TIGIT	RO7247669 and axitinib with or without tiragolumab	Frontline	PFS
NCT03744468	TIM-3, LAG-3, and PD-L1	BGB-A425, tislelizumab, and LBL-007	Locally advanced unresectable or metastatic	ORR
NCT03977467	TIGIT and PD-L1	Tiragolumab and atezolizumab	Progression on prior anti-PD-1 inhibitor	ORR
NCT04913337	ILT2, ILT4, and PD-1	NGM707 alone and with pembrolizumab	Refractory or intolerant to approved therapies	DLT, AEs, DoR, PFS, OS
NCT05215574	ILT3 and PD-1	NGM831 alone and with pembrolizumab	No prior ILT3 inhibition	DLT, AEs, ORR
NCT04691375	TREM2 and PD-1	PY314 alone and with pembrolizumab	Refractory to or relapsed on approved therapies	AEs, DLT
NCT05864144	VISTA and PD-1	SNS-101 alone and with cemiplimab	Refractory to or relapsed on approved therapies	AEs, recommended phase 2 dose, ORR
NCT04773951	BTLA	Icatolimab	Refractory to or relapsed on approved therapies	Safety, tolerability, MTD
NCT05789069	BTLA and PD-1	HFB200603 alone and with tislelizumab	Refractory to at least 2 lines of therapy	AEs, DLT
NCT05229601	OX-40	HFB301001	Progression on at least 2 lines of therapy	AEs, recommended phase 2 dose
NCT05661955	OX-40 and PD-1	BGB-A445 alone and with tislelizumab	Progression on one to three lines of therapy	ORR
NCT04198766	OX-40 and PD-1	INBRX-106 alone and with pembrolizumab	Refractory to or relapsed on approved therapies	AEs, MTD, recommended phase 2 dose
NCT03894618	OX-40 and PD-1	SL-279252	Refractory to or relapsed on approved therapies	AEs, MTD
NCT03809624	4–1BB and PD-1	INBRX-105 alone and with pembrolizumab	Traditional immune checkpoint therapy naïve and refractory allowed	AEs, MTD, recommended phase 2 dose
NCT04895748	A2AR and PD-1	Taminadenant, spartalizumab, and DFF332	Refractory to or relapsed on approved therapies	AEs, DLT
NCT04969315	A2AR	TT-10	Refractory to or relapsed on approved therapies	DLT, recommended phase 2 dose
NCT03454451	CD73, A2AR, and PD-1	Mupadolimab alone, with ciforadenant, and with ciforadenant and pembroliuzmab	Progression on up to 5 prior lines of therapy	DLT, AEs

PFS = progression-free survival, ORR = objective response rate, MTD = maximum tolerated dose, DLT = dose-limiting toxicities, AEs = adverse events, DoR = duration of response.

Table 3. Current active and recruiting clinical trials evaluating vaccines in metastatic RCC.

Trial number	Type of vaccine	Agent(s)	Setting	Primary outcome measures
NCT05329532	Peptide	Modi-1 alone and with pembrolizumab or nivolumab	Prior treatment with anti-angiogenic therapy	AEs, cellular immune response
NCT02950766	Personalized neoantigen	Neovax and ipilimumab	No prior immunotherapy	DLT
NCT05641545	Personalized neoantigen	IVAC-RCC-001 with ipilimumab and nivolumab	No prior systemic therapy	Toxicities and T-cell response
NCT05269381	Personalized neoantigen	Personalized neoantigen vaccine with pembrolizumab	Prior systemic therapy allowed	AEs
NCT03289962	Personalized neoantigen	Autogene cevumeran alone and with atezolizumab	No prior immunotherapy for patients with RCC	DLT, AEs, recommended phase 2 dose
NCT04203901	DC	CMN-001 with ipilimumab and nivolumab vs. ipilimumab and nivolumab	Frontline	OS
NCT00458536	DC-tumor fusion	DC-tumor fusion vaccine alone and with GM-CSF	No prior systemic therapy	AEs
NCT03294083	Virus	Pexastimogene devacirepvec with cemiplimab	Both frontline and prior systemic therapy allowed	MTD, AEs, ORR
NCT02432963	Virus	p53MVA with pembrolizumab	Prior systemic therapy allowed	Tolerability

AEs = adverse events, DLT = dose-limiting toxicities, DC = dendritic cell, OS = overall survival, GM-CSF = granulocyte macrophage colony-stimulating factor, MTD = maximum tolerated dose, ORR = objective response rate.

Table 4. Current active and recruiting clinical trials CAR T-cell therapy in metastatic RCC.

Trial number	Target	Agent(s)	Setting	Primary outcome measures
NCT04969354	CAIX	CAIX-targeted CAR T cell	Up to 2 prior lines of treatment including anti-PD-1/PD-L1 agents	AEs, ORR
NCT04438083	CD70	CTX130	Refractory to all SoC therapies	AEs, ORR
NCT04696731	CD70	ALLO-316	Refractory to prior ICI and VEGF-TKI	DLT
NCT05420519	CD70	CD70–targeted CAR T cell	Refractory to all SoC therapies	AEs, MTD
NCT05518253	CD70	CD70–targeted CAR T cell	Refractory to all SoC therapies	AEs, MTD
NCT05468190	CD70	CD70–targeted CAR T cell	Refractory to all SoC therapies	AEs, MTD
NCT05420545	CD70	CD70–targeted CAR T cell	Refractory to all SoC therapies	AEs, MTD
NCT02830724	CD70	CD70–targeted CAR T cell	Refractory to at least one line of therapy	AEs, ORR
NCT05795595	CD70	CTX131	Refractory to SoC therapies	AEs, ORR
NCT03393936	ROR2 and AXL	CCT301–59 for ROR2, and CCT301–38 for AXL	Refractory to SoC therapies	DLT, ORR

CAIX = carbonic anhydrase IX, AEs = adverse events, ORR = objective response rate, SoC = standard of care, ICI = immune checkpoint inhibitor, VEGF-TKI = vascular endothelial growth factor tyrosine kinase inhibitor, DLT = dose-limiting toxicities, MTD = maximum tolerated dose.