Trial of MEK Inhibitor and PI3K/mTOR Inhibitor in Subjects With Locally Advanced or Metastatic Solid Tumors

An Open-Label, Phase Ib Dose Escalation Trial of Oral Combination Therapy With MSC1936369B and SAR245409 in Subjects With Locally Advanced or Metastatic Solid Tumors

This research trial is testing a combination of two experimental drugs, MSC1936369B (Mitogen-activated protein extracellular signal-regulated kinase (MEK) Inhibitor) and SAR245409 (Phosphatidylinositol 3-kinase (Pi3K)/Mammalian Target of Rapamycin (mTOR) inhibitor), in the treatment of locally advanced or metastatic solid tumors. The primary purpose of the study is to determine the maximum tolerated dose of the drug combination.

Inclusion Criteria:

• Subject with advanced solid tumors for which there is no approved therapy:

  • Advanced solid tumor with diagnosed alteration in one or more of the following genes (PTEN, BRAF, KRAS, NRAS, PI3KCA, ErbB1, ErbB2, MET, RET, c-KIT, GNAQ, GNA11 and/or
  • A histologically or cytologically confirmed diagnosis of one of the following solid tumors: pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma and melanoma

• Subject with archived tumor tissue available for transfer to the Sponsor

• Subject enrolled at lower dose level cohorts and MTD expansion cohorts must have tumor available for biopsy and agree to pre-treatment and on-treatment tumor biopsies

• Subject has measurable or evaluable disease by response evaluation criteria in solid tumors (RECIST) v1.1

• Subject is aged greater than or equal to (>=) 18 years

• Subjects enrolled in disease specific expansion cohorts must fulfill all the inclusion/exclusion criteria listed above with the following restriction to the Inclusion Criterion number 1:

  • Relapsed or refractory Kirsten rat sarcoma viral oncogene homolog (KRAS) or neuroblastoma RAS viral oncogene homolog (NRAS) mutated metastatic non-small cell lung cancer (NSCLC) with no approved therapies, or
  • Relapsed or refractory metastatic triple negative breast cancer defined as estrogen, progesterone and HER2 negative carcinoma of the breast with no approved therapies, or
  • Relapsed or refractory metastatic colorectal cancer (CRC) with dual KRAS and PIK3CA mutation with no approved therapies, or
  • BRAF V600E/K mutated unresectable or metastatic melanoma after progression on B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors

• Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

• Subject has been previously treated with a PI3K inhibitor or a MEK inhibitor and taken off treatment due to treatment related adverse events
• Subject has received:
• Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anti-cancer therapy within 28 days of trial drug treatment
• Any investigational agent within 28 days of trial drug treatment
• Extensive prior radiotherapy on more than 30% bone marrow reserves, or prior bone marrow/stem cell transplantation
• Subject has not recovered from toxicity due to prior therapy
• Subject has poor organ and marrow function as defined in the protocol
• Subject has a history of central nervous system metastases, unless subject has been previously treated for CNS metastases
• Subject has a history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease
• Subject has a history of recent major surgery or trauma within the last 28 days.
• Subject has participated in another clinical trial within the past 30 days
• Other protocol-defined exclusion criteria could apply