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A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands

Trial Status: Active

This primary purpose of this study is to find the recommended dose of LGK974 as a single agent and in combination with PDR001 that can be safely given to adult patients with selected solid malignancies for whom no effective standard treatment is available.

Inclusion Criteria

  • Inclusion Criteria: Diagnosis of locally advanced or metastatic cancer that has progressed despite standard therapy or for which no effective standard therapy exists and histological confirmation of one of the following diseases indicated below: Single Agent Dose escalation part:documented B-RAF mutant colorectal cancer or pancreatic adenocarcinoma. In addition, tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway are eligible with prior agreement with Novartis. Single Agent Dose expansion part: documented B-RAF mutant colorectal cancer with documented RNF43 mutation and/or RSPO fusion or pancreatic adenocarcinoma with documented RNF43 mutation. In addition, patients with tumors of any histological origin with documented genetic alterations upstream in the Wnt signaling pathway (e.g. RNF43 or RSPO fusion) are eligible with prior agreement with Novartis LGK974 with PDR001: Dose escalation: patients with the following cancers that were previously treated with anti-PD-1 therapy and whose best response on that therapy was progressive disease (i.e. primary refractory): melanoma, lung SCC, HNSCC. Patients with esophageal SCC, cervical SCC or TNBC who are either naïve or primary refractory to prior anti-PD-1 therapy. LGK974 with PDR001: Dose expansion: patients with pancreatic cancer, or TNBC, or melanoma, or head and neck cancer. Exclusion Criteria: - Impaired cardiac function - Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of oral LGK974 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) - Brain metastases that have not been adequately treated - Malignant disease other than that being treated in this study - Laboratory abnormalities as specified in the protocol - Osteoporosis, severe or untreated osteopenia - Bone fractures within the past year - Pathologic bone fracture - Active, known or suspected autoimmune disease or severe hypersensitivity reactions to other monoclonal antibodies Other protocol-defined inclusion/exclusion criteria may apply


Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Rachel Feldman
Phone: 310-794-2971


Johns Hopkins University / Sidney Kimmel Cancer Center


Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE


Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: ACTIVE
Wayne State University / Karmanos Cancer Institute

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE


M D Anderson Cancer Center
Status: ACTIVE

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Novartis Pharmaceuticals Corporation

  • Primary ID CLGK974X2101
  • Secondary IDs NCI-2011-03693, 2011-000495-33
  • ID NCT01351103