Refametinib (BAY86-9766) in Combination With Regorafenib (Stivarga, BAY73-4506) in Patients With Advanced or Metastatic Cancer

A Phase 1b/2, Multi-center, Uncontrolled, Open-label, Dose Escalation Study of Refametinib (BAY86-9766) in Combination With Regorafenib (BAY73-4506) in Patients With Advanced or Metastatic Cancer

Phase I: Determine the maximum tolerated dose of combination of Regorafenib with Refametinib through a dose escalation study, all tumor types that meet certain inclusion/exclusion criteria can be entered.

After the recommended dose is determined, the Phase II portion of the study will evaluate tolerability and efficacy of the combination treatment in patients with breast cancer, lung cancer, or colorectal cancer, respectively.

Number of treatment-emergent Adverse Events (AEs) will be reported in Adverse Events section.

Study was originally designed with both Phase I and Phase II part, but sponsor decided not to conduct Phase 2 part due to strategic portfolio re-prioritization.

Inclusion Criteria:

• Criteria for the Phase 1b:

  • Patients with locally advanced or metastatic solid tumors who have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; is not a candidate for, or is unwilling to undergo, standard therapy in cases where no curative option exists.

• Cohort-specific criteria for Phase 2:

  • CRC (Colorectal cancer): Patients with metastatic CRC and known KRAS (Kirsten rat sarcoma viral oncogene homolog) status who are eligible for treatment with regorafenib in accordance with the approved labeling.
  • NSCLC (Non-small-cell lung cancer): Patients with NSCLC and known KRAS status after platinum based chemotherapy.
  • Breast cancer: Patients with Her-2 negative breast cancer after anthracycline and taxane based chemotherapy.

• Baseline tumor tissue to conduct molecular and / or genetic studies should be available from all study patients enrolled in this study. (optional in Phase 1b)

• Patients must have at least one uni-dimensional measurable lesion by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST)version 1.1. (applicable only in Phase 2)

• Male or female patients ≥ 18 years of age (only female patients in breast cancer cohort of Phase 2).

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Life expectancy of at least 3 months

• Adequate bone marrow, liver and renal function

• Cardiac function within normal range

Exclusion Criteria:

• Prior treatment with refametinib or regorafenib.

• Metastatic brain or meningeal tumors

• Uncontrolled hypertension despite optimal medical management

• History of cardiac disease

• Arterial or venous thrombotic or embolic events

• Any hemorrhage or bleeding event

• History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).

• Any condition that was unstable or which could jeopardize the safety of the patient and his/her compliance in the study.

• Excluded previous therapies and medications:

  • Radiotherapy within 3 weeks prior to start of treatment
  • Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 28 days or 5 drug half-lives (if drug half-life in patients is known), whichever is shorter (or within 6 weeks for mitomycin C) before start of the study treatment