1112P - Five-year survival after intermittent targeted therapy and anti-PD1 in stage IV melanoma: An update of the IMPemBra trial

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

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.