A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer

• Low-grade Serous Ovarian Cancer
• Low-grade Serous Fallopian Tube Cancer
• Low-grade Serous Peritoneal Cancer

• Drug: MEK162, MEK inhibitor; oral
  multiple dose, single schedule
• Drug: Physician's choice chemotherapy

  Patients will receive one of the following chemotherapies as determined by the physician:

  • Liposomal doxorubicin, anthracycline antibiotic; intravenous (multiple dose, single schedule)
  • Paclitaxel, mitotic inhibitor; intravenous (multiple dose, single schedule)
  • Topotecan, topoisomerase 1 inhibitor; intravenous (multiple dose, single schedule)

• Experimental: MEK162
  Intervention: Drug: MEK162, MEK inhibitor; oral
• Active Comparator: Physician's choice chemotherapy
  Intervention: Drug: Physician's choice chemotherapy

Key Inclusion Criteria:

• Diagnosis of LGS carcinoma of the ovary, fallopian tube or primary peritoneum (invasive micropapillary serous carcinoma or invasive grade 1 serous carcinoma), confirmed histologically and verified by central pathology review.
• Recurrent or persistent measurable disease that has progressed (defined as radiological and/or clinical progression; an increase in cancer antigen [CA]-125 alone is not sufficient) on or after last therapy (i.e., chemotherapy, hormonal therapy, surgery) and is not amenable to potentially curative intent surgery, as determined by the patient's treating physician.
• Must have received at least 1 prior platinum-based chemotherapy regimen but have received no more than 3 lines of prior chemotherapy regimens, with no limit to the number of lines of prior hormonal therapy. Front-line therapy may include neoadjuvant and adjuvant therapy and will be counted as 1 prior systemic regimen. Biological therapy (e.g. bevacizumab) administered as a single agent is considered a prior systemic regimen and not a prior chemotherapy regimen. Maintenance therapy is not considered its own regimen but should be included with the regimen that it follows.
• Available archival tumor sample (excisional or core biopsy) for confirmation of LGS carcinoma diagnosis. If adequate archival tumor sample is not available, willingness to consent to tissue biopsy.
• Suitable for treatment with at least one of the physician's choice chemotherapy options (liposomal doxorubicin, paclitaxel or topotecan) as determined by the Investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Additional criteria exist.

Key Exclusion Criteria:

• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
• Prior therapy with a MEK or BRAF inhibitor.
• History of Gilbert's syndrome.
• Impaired cardiovascular function or clinically significant cardiovascular diseases.
• Uncontrolled or symptomatic brain metastases that are not stable or require steroids, are potentially life-threatening or have required radiation within 28 days prior to first dose of study treatment.
• Concomitant malignancies or previous malignancies with less than a 5-year disease-free interval at the time of first dose of study treatment; patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or ductal carcinoma in situ may be enrolled irrespective of the time of diagnosis.
• Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or active hepatitis C.
• Prior randomization into this clinical study.
• Additional criteria exist.