Methods: In Part 2, 125 pts with V600 BRAF mutant solid tumors enrolled, including 77 melanoma pts with no prior BRAFi, and measurable disease according to RECIST 1.1. Pts were treated on 4 escalating dose levels of dabrafenib/trametinib (mg BID/mg QD): 75/1, 150/1, 150/1.5, 150/2. Demographic and efficacy data for the 77 melanoma pts with no prior BRAFi and safety data for all 125 Part 2 pts are reported.
Results: Among 77 melanoma pts, median age was 52 years, 61% male, 57% ECOG PS of 0, 91% V600E, 65% M1c stage, 26% prior brain metastases, and 52% LDH > ULN. Confirmed ORR was 56% (95% CI: 44.1%-67.2%) with 4 CR, 39 PR, 29 SD and, 3 PD. Confirmed response rate for each dose level, respectively, was 67% (n=6), 64% (n=22), 48% (n=25), and 54% (n=24). Median PFS (months) for each dose level, respectively, was: 8.7, 8.3, 5.5; PFS is not mature for 150/2. Overall PFS was 7.4 (95% CI: 5.5-9.2). Among the 125 pts, there were 2 grade (G) 5 adverse events (AEs), pneumonia and hyponatraemia. The most common G3/4 AEs were pyrexia (n=6, 5%), fatigue (n=6, 5%) and dehydration (n=6, 5%). Skin toxicity ≥ G2 occurred in 17 (14%) pts. Cutaneous squamous cell carcinoma occurred in 3 (2%) pts and actinic keratoses in 2 (2%).
Conclusions: The combination of dabrafenib/trametinib has an acceptable safety profile, with a lower incidence of MEKi-related rash and BRAFi-induced hyperproliferative skin lesions compared with the single agents. The clinical activity of dabrafenib/trametinib observed in pts with V600 BRAF mutant metastatic melanoma is encouraging and will be investigated further in a phase III trial.
|Number of pages||1|
|Journal||Journal of Clinical Oncology|
|Issue number||Supplement 15|
|Publication status||Published - 20 May 2012|
|Event||48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) - Chicago, United States|
Duration: 1 Jun 2012 → 6 Jun 2012