Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors

Inclusion Criteria (All):

- Written informed consent must

- Patient has histologically and/or cytologically confirmed malignancies:

Phase I:

• Patients with advanced or metastatic solid tumors who have failed at least one prior line
of systemic antineoplastic therapy in the advanced setting without a standard of care
treatment option available;

Phase II:

- Advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior
systemic antineoplastic therapies in the advanced setting

- Advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic
antineoplastic therapies in the advanced setting without a standard of care treatment
option available. Testing for KRAS mutation in patients with CRC using locally
approved diagnostic kit will be used for eligibility.

- Phase II only: patient must have measurable disease

- Patient has an ECOG performance status 0 or 1.

- Patient has adequate bone marrow and organ function

- Patient must have specified laboratory values within normal limits or corrected to
within normal limits with supplements before the first dose of study medication on
Cycle 1 Day 1:

- Standard 12-lead ECG values defined

Exclusion Criteria:

Phase II only:

• Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.

Phase I and Phase II:

- Patient with a known hypersensitivity to the study drugs or any of the excipients of
ribociclib or trametinib.

- Patient is concurrently using other anti-cancer therapy.

- Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation
≤ 2 weeks prior to Cycle 1 Day 1

- Patient has received local therapy to liver ≤ 3 months of C1D1

- History of liver disease as follow:

- Cirrhosis

- Autoimmune hepatitis

- Active viral hepatitis

- Portal hypertension

- Drug induced liver steatosis

- Prior systemic anti-cancer treatment within 28 days prior to Cycle 1 Day 1

- Prior therapy with anthracyclines at cumulative doses of 450 mg/ m2 or more for
doxorubicin or 900 mg/m2 or more for epirubicin.

- Patient is currently receiving warfarin or other coumadin derived anti-coagulant

- Patient has a history of deep venin thrombosis or pulmonary embolism within 6 months
of screening.

- Patient has a concurrent malignancy or malignancy within 3 years prior to Cycle 1 Day
1, with the exception of adequately treated basal or squamous cell carcinoma or
curatively resected cervical cancer.

- Patients with central nervous system (CNS) involvement

- Patient has impairment of GI function or GI disease that may significantly alter the
absorption of the study drugs

- History of interstitial lung disease or pneumonitis.

- Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality

- Patient is currently receiving any strong inducers or inhibitors of CYP3A4/5 and/or
Substances that have a narrow therapeutic window and are predominantly metabolized
through CYP3A4/5 and cannot be discontinued 7 days prior to Cycle 1 Day 1:

- Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks
prior to starting study drug, or who have not fully recovered from side effects of
such treatment.

- History of retinal vein occlusion (RVO)

Other protocol-defined inclusion/exclusion criteria may apply.