Table 1.

Statistical aspects of SATs

Medicinal product	Trial(s)	Therapeutic area	Biomarker-based indication	Available therapies in treatment setting	Sample size calculationsa	Lower bound of the 95% CI for ORR to be ruled out	Justification	Ref.
Alectinib	NP28761	Lung cancer	Yes	Chemotherapy	Yes	35%	Not provided	20
	NP28673	Lung cancer		Chemotherapy	Yes	35%	Not provided	21
Amivantamab	EDI1001	Lung cancer	Yes	Chemotherapy or immunotherapy	Yes	12%	Single-agent chemotherapy as the benchmark	22
Avapritinib	BLU-285-1101	Sarcoma	Yes	Tyrosine kinase inhibitors	Yes	10%	Benchmarked against available therapies	23
Avelumab	EMR100070-003	Skin cancer	No	Chemotherapy	Yes	20%	Absence of literature documenting treatment outcomes for second-line patients	24
Cemiplimab	2810-ONC-1540	Skin cancer	No	EGFR inhibitors and/or chemotherapy	Yes	laCSCC 25%	Based on previous studies	25
					Yes	mCSCC 15%	Based on previous studies	26
Ceritinib	CLDK378X2101	Lung cancer	Yes	Chemotherapy	No	Not specified	Not applicable	27
Crizotinib	A8081001	Lung cancer	Yes	Chemotherapy	No	Not specified	Not applicable	28
Dostarlimab	4010-01-001	Endometrial cancer	Yes	Chemotherapy or bevacizumab	Yes	20%	Expected ORR for conventional therapy	29
Entrectinibb	ALKA-372-001, RXDX-101-01, and RXDX-101-03	Lung cancer	Yes	Crizotinib	Yes (on precision and implicitly on power)	50%	Observed with standard-of-care ROS1 fusion-positive NSCLC treatment	30
		Cancer		No appropriate available therapies	Yes (on precision and implicitly on power)	30%	Not provided	31
Larotrectinibb	LOXO-TRK-14001, LOXO-TRK-15002, and LOXO-TRK-15003	Cancer	Yes	No appropriate available therapies	Yes	30%	Consistent with the response rates seen with approved targeted therapies in genetically defined patient populations who have progressed on prior therapies	32
Lorlatinib	B7461001	Lung cancer	Yes	(Platinum-based) chemotherapy/immunotherapy	No	Not specified	Not applicable	33
Osimertinibc	AURA extension	Lung cancer	Yes	(Platinum-based) chemotherapy or tyrosine kinase inhibitor rechallenge	Yes (based on precision)	Not specified	Not applicable	34
	AURA 2			(Platinum-based) chemotherapy or tyrosine kinase inhibitor rechallenge	Yes (based on precision)	Not specified	Not applicable	35
Pemigatinib	INCB 54828-202	Bile duct cancer	Yes	Chemotherapy	Yes	15%	Proportions of patients with an objective response reported by previous studies	36
Pralsetinib	BLU-667-1101	Lung cancer	Yes	(Platinum-based) cytotoxic chemotherapy and/or immunotherapy	Yes	48%	Not provided	37
				Chemotherapy ± ramucirumab or immunotherapy	Yes	23%	Not provided
Rucaparibb	CO-338-010	Ovarian cancer	Yes	Chemotherapy	No	Not specified	Not applicable	38
	CO-338-017			Chemotherapy	No	Not specified	Not applicable	39
Selpercatinib	LOXO-RET-17001	Lung cancer	Yes	Chemotherapy ± ramucirumab or immunotherapy	Yes	NSCLC 30%	Consistent with the response rates seen with approved targeted therapies in molecularly defined populations who failed prior therapies	40
		Thyroid cancer		Treatment options in these settings are limited—tyrosine kinase inhibitors rechallenge—or even lacking	Yes	MTC 20%	The limited treatment options	41
					No	TC Not specified	Not applicable	41
Trastuzumab deruxtecan	DS8201-A-U201	Breast cancer	Yes	HER2-targeted therapy in combination with chemotherapy	Yes	20%	Not provided	42
Vismodegib	SHH4476g	Skin cancer	No	Radiation therapy or chemotherapy	Yes	mBCC 10%	No therapeutic options exist for these patients and spontaneous responses have not been reported in this diseased	43
					Yes	aBCC 20%	No therapeutic options exist for these patients and spontaneous responses have not been reported in this diseased	43

Therapeutic areas are depicted in color: lung cancer in orange, skin cancer in yellow, cancer (general) in blue, and remaining areas in green. Information was retrieved from EPARs and complemented by scientific publications and protocols, if available and necessary.

aBCC, advanced basal cell carcinoma; CI, confidence interval; HER2, human epidermal growth factor receptor 2; laCSCC, locally advanced cutaneous squamous cell carcinoma; mBCC, metastatic basal cell carcinoma; mCSCC, metastatic cutaneous squamous cell carcinoma; MAH, marketing authorization holder; MTC, medullary thyroid cancer; NSCLC, non-small-cell lung cancer; ORR, objective response rate; ROS1, c-ros oncogene 1; TC, thyroid cancer.

^aSample size calculations were based on power unless otherwise specified.

^bIntegrated analysis was carried out based on two or three trials.

^cSeparated and integrated analysis was carried out for trials AURA and AURA2.

^dBased on protocol.