Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell

Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer

ClinicalTrials.gov: ID NCT01336634
Sponsor: Novartis Pharmaceuticals
Information provided by: Novartis (Novartis Pharmaceuticals) (Responsible Party)
Last Update Posted: 2022-04-04

Brief Summary:
This was a Phase II, multicenter, non-randomized, open-label study to assess the efficacy, safety, and tolerability of dabrafenib administered as a single agent and in combination with trametinib in stage IV disease to subjects with BRAF mutant advanced non-small cell lung cancer. Central confirmation testing for the BRAF V600E mutation was performed and a sufficient number of subjects were enrolled with the intent of having at least 125 centrally confirmed subjects among the three cohorts.

Detailed Description:
Subjects enrolled in Cohort A (Monotherapy Population) were required to have relapsed or progressed on at least one platinum based chemotherapy regimen prior to enrollment (i.e. dabrafenib was no less than second line treatment for metastatic disease). Additional lines of prior anti-cancer therapy were allowed. Subjects received dabrafenib as a single agent at the recommended dose of 150 mg twice daily. A 2 stage design with a planned sample size of 40 subjects was initially used for Cohort A.

Subjects enrolled in Cohort B (Combination Second-Line Population) were required to have relapsed or progressed on at least one platinum based chemotherapy prior to enrollment but did not receive more than 3 prior systemic anti-cancer therapies (i.e. dabrafenib/trametinib were second, third, or fourth line treatment for metastatic disease). Subjects received the recommended dose of both drugs (dabrafenib 150 mg twice daily and trametinib 2 mg once daily).

Subjects enrolled in Cohort C (Combination First-Line Population) did not receive prior systemic anti-cancer therapies for metastatic disease (i.e. dabrafenib/trametinib was first line treatment for metastatic disease). Subjects received the recommended dose of both drugs (dabrafenib 150 mg twice daily and trametinib 2 mg once daily).

Crossover: Subjects receiving and adequately tolerating dabrafenib as a single agent and who continued to meet the inclusion and exclusion criteria (including the additional criteria for combination therapy) had the option to crossover to dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination treatment at the time of radiologic disease progression with prior approval from a Medical Lead. If a subject was receiving less than 150 mg BID of dabrafenib at the time of the crossover, the subject was to continue at the lower dose of dabrafenib when initiating combination therapy.

Official Title:
A Phase II Study of the BRAF Inhibitor Dabrafenib as a Single Agent and in Combination With the MEK Inhibitor Trametinib in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer

Intervention / Treatment:
- Drug: Dabrafenib
- Drug: Trametinib

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