A Basket Trial Example: Vemurafenib in BRAF V600 Mutation–Positive Cancers

 Brief Summary:

This open-label, multi-center study will assess the efficacy and safety of vemurafenib in participants with BRAF V600 mutation-positive cancers (solid tumors and multiple myeloma, except melanoma and papillary thyroid cancer) and for whom vemurafenib is deemed the best treatment option in the opinion of the investigator. Participants will receive twice daily oral doses of 960 mg vemurafenib until disease progression, unacceptable toxicity, or withdrawal of consent. The safety and efficacy of vemurafenib in combination with cetuximab in a subset of participants with colorectal cancer will also be assessed.

Official Title:

An Open-label, Phase II Study of Vemurafenib in Patients With BRAF V600 Mutation-positive Cancers


How is the study designed ?

Allocation  : Non-Randomized

Interventional Model  : Parallel Assignment

Masking  : None (Open Label)



How is the study measuring ?





Results

Trial M028072 (VE Basket) initiated on April 11, 2012, and completed on October 27, 2016. The data cutoff for the application submission was January 12, 2017. The trial enrolled 208 patients into seven different cohorts. Twenty‐two patients with ECD with BRAFV600 mutation enrolled in Cohort 7a. Enrolled ECD patients had a median age of 58.5 years (34–77 years), had a slight male predominance (55%), and were predominantly white (96%). Eastern Cooperative Oncology Group (ECOG) scores at baseline were mostly 1 (54%), with 23% of patients having a score of 2, 18% having a score of zero, and 5% “not applicable.” Fifteen patients (68%) had at least one prior systemic therapy for ECD. At the time of data cutoff, all patients were no longer receiving study treatment and had discontinued from the study.

Efficacy

The overall response rate (ORR) was 54.5% (95% confidence interval: 32.2–75.6). One patient had a CR, and eleven had PRs (Table 2). The remaining nine patients had stable disease, and one patient's outcome was not measurable. The median DoR was not estimable with a median duration of follow‐up of 26.6 months (3–44.3 months). The median time to response was 11 months (3.7–14.6 months). The median time to treatment discontinuation was 14.2 months (1.6–44.2 months). The median PFS and OS were not estimable.



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