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Spartalizumab plus dabrafenib and trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600-mutant unresectable or metastatic melanoma: Results from the randomized part 3 of the phase III COMBI-i trial
Nathan, P. Dummer, R. Long, G. V. Ascierto, P. A. Tawbi, H. A. Robert, C. Rutkowski, P. Leonov, O. Dutriaux, C. Mandala, M.
Nathan, P.
Dummer, R.
Long, G. V.
Ascierto, P. A.
Tawbi, H. A.
Robert, C.
Rutkowski, P.
Leonov, O.
Dutriaux, C.
Mandala, M.
Citations
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Abstract
Background: Treatment (tx) with immune checkpoint inhibitors + targeted therapy
may induce durable and deeper responses in a higher proportion of pts. Results from
the safety run-in (part 1) and biomarker cohort (part 2) of COMBI-i (NCT02967692)
have been previously reported. Part 3 is a global, placebo (PBO)-controlled, doubleblind,
Phase III study evaluating the anti -PD-1 antibody Sparta + Dab and Tram in pts
with previously untreated BRAF V600 -mutant unresectable or metastatic melanoma.
Here we report the primary analysis for part 3 of COMBI-i.
Methods: Pts were randomized 1:1 to receive Sparta 400 mg IV Q4W + Dab 150 mg
orally BID + Tram 2 mg orally QD vs PBO-DabTram. The statistical plan ensured 80%
power assuming a 5-month tx delay. The primary endpoint is investigator-assessed
progression-free survival (PFS) using RECIST 1.1; significance threshold was P < .025
[equivalent HR < 0.801]. Overall survival (OS) is a key secondary endpoint.
Results: 532 pts were randomized to receive Sparta-DabTram (n = 267) or PBODabTram
(n = 265). At the data cutoff (July 1, 2020), median follow-up was 27.2 mo.
Baseline characteristics were balanced across tx arms. Sparta-DabTram did not
significantly improve PFS vs PBO (median PFS, 16.2 mo vs 12.0 mo; HR, 0.82 [95% CI,
0.655-1.027]; P = .042). Estimated 12- and 24-mo PFS rates with Sparta-DabTram vs
PBO were 58% vs 50% and 44% vs 36%, respectively. While OS was not formally
tested, median OS was not reached (NR) across tx arms (HR, 0.785). The objective
response rate was 69% in the Sparta-DabTram arm (complete response rate [CRR],
20%) vs 64% in the PBO arm (CRR, 18%); median duration of response was NR vs 20.7
mo, respectively. Tx-related adverse events (TRAEs) grade ≥ 3 occurred in 55% vs 33%
of pts treated with Sparta-DabTram vs PBO. TRAEs leading to discontinuation of all 3
study drugs occurred in 12% vs 8% of pts, respectively.
Conclusions: The primary endpoint was not met. Sparta-DabTram did not significantly
improve PFS vs PBO-DabTram; analyses interrogating OS benefit are ongoing. AE
management was challenging and resulted in frequent dose adaptations.
Description
Date
2020
Publisher
Collections
Keywords
Type
Article
Citation
Nathan P, Dummer R, Long GV, Ascierto PA, Tawbi HA, Robert C, et al. LBA43 Spartalizumab plus dabrafenib and trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600–mutant unresectable or metastatic melanoma: Results from the randomized part 3 of the phase III COMBI-i trial. Annals of Oncology. 2020;31:S1172-S.