Neoplasms

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