Company Decision

This is an open-label, multicenter, non-randomized, single arm, phase II study to assess efficacy and safety of the dabrafenib and trametinib combination in Japanese patients with any line, stage IV NSCLC harboring a confirmed BRAF V600E mutation.

Patients will receive oral dabrafenib twice daily and oral trametinib once daily combination therapy. Patients may continue study treatment until disease progression, unacceptable adverse events, start of a new anti-cancer therapy, consent withdrawal, death, or end of the study. Patients who have met the criteria for disease progression (PD) according to RECIST v1.1 may continue to receive study treatment if the investigator believes the patient is receiving clinical benefit and the patient is willing to continue on study treatment. After discontinuation of study treatment, all patients will be followed for survival until death, lost to follow-up, withdrawal of consent, or end of study.

Inclusion Criteria:

• Histologically- or cytologically-confirmed diagnosis of NSCLC stage IV (according to AJCC Staging 7th Edition)
• Presence of a BRAF V600E mutation in lung cancer tissue. BRAF V600E mutation tested by local laboratory (e.g. study center laboratory, local laboratory company) with proper quality control and license to operation by local health authority is allowed.
• Measurable disease according to RECIST v1.1.

Exclusion Criteria:

• Previous treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, encorafenib, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, cobimetinib, binimetinib, AZD6244, and RDEA119) prior to start of study treatment

• Patients with brain metastases are excluded if their brain metastases are:

  • Symptomatic OR
  • Treated (surgery, radiation therapy) but not clinically and radiographically stable 3 weeks after local therapy (as assessed by contrast enhanced magnetic resonance imaging [MRI] or computed tomography [CT]), OR
  • Asymptomatic and untreated but >1 cm in the longest dimension

• History of malignancy with confirmed activating RAS mutation at any time.

• History of interstitial lung disease or pneumonitis

• A history or current evidence of retinal vein occlusion (RVO)

• Current evidence of unstable aneurysm or one that needs treatment

Other protocol-defined inclusion/exclusion may apply.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com