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

A Phase I/II Study of Safety and Efficacy of Ribociclib (LEE011) in Combination With Trametinib (TMT212) in Patients With Metastatic or Advanced Solid Tumors

Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized.

Upon careful review of all available efficacy and safety data from the study phase Ib part, Novartis decided to not start the study phase II part.

This decision was in no means triggered by an unfavorable safety profile of the combination. The observed safety profile of the combination represents contributions of the individual safety profile of trametinib and ribociclib.

No new safety signals were observed.

The study was closed early in line with protocol Section 4.4.

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.