Patient case: 57-year-old male with lung adenocarcinoma; genetic feature: KRAS (G12V), high tumor mutational burden

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

Summary: 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.


Eligibility: 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.

Relevance to patient case: not relevant