. 2021 Apr 15;13(8):1905. doi: 10.3390/cancers13081905

Table 1.

Summary of phase II randomized controlled and single-arm trials using neoadjuvant contemporary therapies for resectable stage III/IV melanoma.

Trial	Design	Patient Population	Regimen	N	Grade 3–4 AEs (% pts)	pCR (%)	Median RFS (95% CI) (mo)	Med FU (IQR) (mo)
NCT02231775 Amaria et al. Lancet Oncol 2018	Randomized, open-label, phase II	Stage IIIB-D, resectable IV BRAF V600E/K	dab + tram × 8 w → Surgery → dab + tram × 44 w	14	15	50	19.7 (16.2-NR) HR 0.016 (p < 0.0001)	18.6 (14.6–23.1)
NCT02231775 Amaria et al. Lancet Oncol 2018	Randomized, open-label, phase II	Stage IIIB-D, resectable IV BRAF V600E/K	Upfront surgery + consideration of adjuvant therapy	7	NA	NA	2.9 (1.7-NR)	18.6 (14.6–23.1)
NCT01972347 NeoCombi Long et al. Lancet Oncol 2019	Single-arm, open-label, phase II	Clinical Stage IIIB-C BRAF V600E/K	dab + tram × 12 w → Surgery → dab + tram × 40 w	35	29	49	23.3 (17.7-NR)	27 (21–36)
NTR4654 REDUCTOR trial Blankenstein et al. J Clin Oncol 2019	Single-arm, phase II	Locally advanced Stage III, oligometastatic IV BRAF V600E/K	dab + tram × 8 w → Surgery	20	15	35	9	28
NCT02519322 Amaria et al. Nature 2018	Randomized, phase II	Clinical stage IIIB-D, oligometastatic IV	nivo3 q2w × 4	12	8	25	NR	15
NCT02519322 Amaria et al. Nature 2018	Randomized, phase II	Clinical stage IIIB-D, oligometastatic IV	ipi3 + nivo1 q3w × 3	11	73	45	NR	15.6
NCT02977052 OpACIN-neo Rozeman et al. Lancet Oncol 2019 Rozeman et al. ASCO 2020	Randomized, open-label, phase II	Resectable stage IIIB-D (nodal metastases only)	ipi3 + nivo1 q3w × 2	30	40	47	NR	24.6
			ipi1 + nivo3 q3w × 2	30	20	57
			ipi3, 3w later: ipi3 + nivo3, 2w later: nivo3	26	50	23
NCT02977052 PRADO Blank et al. ASCO 2020	Extension cohort of OpACIN-neo trial	Resectable stage IIIB-D (nodal metastases only)	Marker in ILN → ipi1 + nivo3 q3w × 2 → ILN resection → no further therapy if MPR vs. TLND ± adjuvant nivo or TT × 52w	99	24	61	NR	NR
NCT02211131 Andtbacka et al. J Clin Oncol 2018 Dummer et al. J Clin Oncol 2019 Dummer et al. Annals Onc 2019	Randomized, open label, phase II	Resectable stage IIIB-D/IV1a and ≥ 1 injectable cutaneous, subcutaneous or nodal lesion	6 × intralesional T-VEC → Surgery	76	NA	21	NR	31.2
	Randomized, open label, phase II		Surgery alone	74	NA	NA	NR	31.2
NCT03618641 Davar et al. J Imm Cancer 2019	Single-arm, phase II	Stage IIIB-D	Subcutaneous CMP-001 × 1, then intralesional CMP-001 × 7 + nivo 240 mg q2w × 3 → Surgery → nivo 480 mg q4w + s/c CMP-001 q4w × 48w	16	NA	76	NA	NA

AEs, adverse events. pCR, pathologic complete response. RFS, relapse-free survival. NR, not reached. FU, follow-up. HR, hazard ratio. NA, not assessed. ILN, index lymph node. MPR, major pathologic response. TLND, therapeutic lymph node dissection. TT, targeted therapy.