Abstract 1112P
Background
IMPemBra was the first trial testing intermittent, short-term, dabrafenib and trametinib (DT) plus pembrolizumab (PEM) in patients with stage IV melanoma, with the concept of inducing stronger immune infiltration in the tumor, translating in better long-term outcome. The adverse event (AE) rate of intermittent DT was lower than for continuous triple therapy. While addition of DT only slightly increased the best overall response from 75% to 88%, the 3-year progression free survival (PFS) and overall survival (OS) was higher for the DT+PEM cohorts as compared to PEM only (53% vs 25%, and 64% vs 33%, respectively), no statistically significant differences were found probably due to small patient cohorts. Here we present the updated 5-year PFS and OS data from patients enrolled in the IMPemBra trial.
Methods
32 treatment-naïve patients with stage IV melanoma harboring a BRAFV600E/K mutated melanoma were enrolled. All patients started with 2 cycles of PEM 200mg (Q3W), followed by randomization to either PEM monotherapy (cohort 1); PEM in combination with either dabrafenib (D) 150 mg BID + trametinib (T) 2mg QD intermittent for 2x1 week (cohort 2), 2x2 weeks (cohort 3) or continuously for 6 weeks (cohort 4). From week 12 and onwards, all cohorts continued PEM for a maximum of in total 2 years.
Results
With a median follow-up of 59.6 months, the estimated 5-year RFS and OS rates were 25% and 50% in cohort 1, 63% and 63% in cohort 2, 38% and 75% in cohort 3, and 60% and 75% in cohort 4, respectively, as shown in the table. We observed no differences in the quantity and type of subsequential therapies between the cohorts. No new safety signals were identified. Table: 1112P
5-year clinical outcomes | |||||||
5-year PFS (95% CI) | 5-year OS (95% CI) | ||||||
All patients (n=32) | 46% (32.5-67.3) | 66% (51.1-84.3) | |||||
Cohort 1 (n=8) | 25% (7.5-83.0) | 50% (25.0-100) | |||||
Cohort 2 (n=8) | 63% (36.5-100.0) | 63% (36.5-100) | |||||
Cohort 3 (n=8) | 38% (15.3-91.7) | 75% (50.3-100) | |||||
Cohort 4 (n=8) | 60% (33.1-100) | 75% (50.3-100) | |||||
Subsequential therapies | |||||||
Subsequential treatment | Anti-PD1 | Anti-CTLA-4 | Anti-CTLA-4 + anti-PD1 | Targeted therapy | Surgery | Other | |
All patients | 18 (56%) | 6 (33%) | 2 (11%) | 7 (39%) | 14 (78%) | 2 (11%) | 1 (6%) |
Cohort 1 | 6 (75%) | 1 (13%) | 1 (13%) | 3 (38%) | 5 (63%) | 1 (13%) | |
Cohort 2 | 3 (38%) | 2 (25%) | 3 (38%) | ||||
Cohort 3 | 5 (63%) | 3 (38%) | 3 (38%) | 1 (13%) | |||
Cohort 4 | 4 (50%) | 2 (25%) | 1 (13%) | 2 (25%) | 3 (38%) | 1 (13%) |
Conclusions
This update from the IMPemBra trial confirms the previous findings indicating that the addition of short-term DT to PEM can induce long-lasting responses upon PEM that appears to be superior compared to PEM monotherapy. This improved PFS translated also into a promising increase in 5-year OS compared to PEM in first line therapy.
Clinical trial identification
NCT02625337.
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute - Antoni van Leeuwenhoek Amsterdam.
Funding
MSD.
Disclosure
B. van de Wiel: Non-Financial Interests, Personal, Advisory Role: BMS. D. Van Den Broek: Financial Interests, Institutional, Advisory Role: Roche Diagnostics. S. Wilgenhof: Financial Interests, Institutional, Advisory Board: Eisai, Pfizer, Novartis, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharp & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharp & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editorial Board ESMO Open: ESMO; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board: Kidney Cancer. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Advisory Board: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Immagene; Financial Interests, Personal, Stocks/Shares, intention to develop IFN signature algorithm: NewCo, no name yet; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, NanoString, 4SC; Other, pending patent: WO 2021/177822 A1. All other authors have declared no conflicts of interest.
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