Table 9. Summary of Clinical Outcomes of Second-Line Key Trials.

	RESORCE [844]		CELESTIAL [845]		REACH-2 [847]		CheckMate-040 [853]	CheckMate-040 [855]	KEYNOTE-394 [846]
	REG	PBO	CAB	PBO	RAM	PBO	NIV	NIV + IPI	PEM	PBO
Number of patients allocated	379	194	470	237	197	95	214*	50†	300	153
Median OS (months)	10.6	7.8	10.2	8.0	8.5	7.3	9-month 74%	22.8	14.6	13.0
HR (95% CI)	0.63 (0.50–0.79); p < 0.0001		0.76 (0.63–0.92); p = 0.005		0.710 (0.531–0.949); p = 0.0199		NA	NA	0.79 (0.63–0.99); p = 0.0180
Median PFS (months)	3.1	1.5	5.2	1.9	2.8	1.6	4.0	NA	2.6	2.3
HR (95% CI)	0.44 (0.37–0.56); p < 0.0001		0.44 (0.36–0.52); p < 0.001		0.452 (0.339–0.603); p < 0.0001		NA	NA	0.74 (0.60–0.92); p = 0.0032
Median TTP (months)	3.2	1.5	NA	NA	3.0	1.6	4.1	NA	3.8	2.8
HR (95% CI)	0.44 (0.36–0.55); p < 0.0001		NA		0.427 (0.313–0.582); p < 0.0001		NA	NA	0.69 (0.54–0.88); p = 0.0011
ORR/CR (%)	11.0/1.0	4.0/0.0	4.0/0.0	< 1.0/0.0	5.0/0.0	1.0/0.0	20.0/1.0	32.0/8.0	12.7/2.0	1.3/0.7
DCR (%)	65.0	36.0	64.0	33.0	59.9	38.9	64.0	54.0	51.0	47.1
Median duration of treatment (months)	3.6	1.9	3.8	2.0	12 weeks	8 weeks	NA	5.1	NA	NA
Median duration of response (months)	NA	NA	NA	NA	NA	NA	9.9	17.5	23.9	5.6
Response evaluation	mRECIST		RECIST v1.1		RECIST v1.1		RECIST v1.1	RECIST v1.1	RECIST v1.1

^*214 patients in the dose expansion phase, ^†Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (4 doses) followed by nivolumab 240 mg intravenously every 2 weeks.

REG = regorafenib, PBO = placebo, CAB = cabozantinib, RAM = ramucirumab, NIV = nivolumab, IPI = ipilimumab, PEM = pembrolizumab, OS = overall survival, HR = hazard ratio, CI = confidence interval, NA = not available, PFS = progression-free survival, TTP = time-to-progression, ORR = objective response rate, CR = complete response, DCR = disease control rate, mRECIST = modified Response Evaluation Criteria in Solid Tumors, RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1