A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands
Completed · Phase 1
Conditions studied: Pancreatic Cancer, BRAF Mutant Colorectal Cancer, Melanoma, Triple Negative Breast Cancer, Head and Neck Squamous Cell Cancer, Cervical Squamous Cell Cancer, Esophageal Squamous Cell Cancer, Lung Squamous Cell Cancer
In brief
The primary purpose of this study was 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 that had progressed despite standard therapy or for which no effective standard therapy existed.
Key facts
- Study ID
- NCT01351103
- Run by
- Novartis Pharmaceuticals
- People needed
- 185
- Starts
- 2011-12-01
- Expected to finish
- 2024-06-17
- Last updated by the study team
- 2025-06-13
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- 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:
- cutaneous melanoma that was primary refractory to prior anti-PD-1 therapy, defined as a best response of progressive disease or stable disease for <= 4 months, or disease recurrence with the first 6 months of adjuvant therapy. Patients with BRAF V600-mutant melanoma must have also received and been failed by prior systemic therapy with BRAF V600 inhibitor, with or without a MEK inhibitor.
- Cutaneous melanoma with acquired resistance to prior anti-PD-1 therapy, defined as progressive disease following response (PR or CR) or following stable disease for > 4 months. Patients with BRAF V600-mutant melanoma must have also received and been failed by prior systemic therapy with a BRAF V600 inhibitor, with or without a MEK inhibitor.
You may not qualify if…
- Impaired cardiac function
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of 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, 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
Where it is running
- UCLA School of Medicine — Los Angeles, California, United States
- Sidney Kimmel Comprehensive Cancer Center Johns Hopkins — Baltimore, Maryland, United States
- Dana Farber Cancer Institute SC-7 — Boston, Massachusetts, United States
- University of Michigan Comprehensive Cancer Center Onc Dept. — Ann Arbor, Michigan, United States
- Karmanos Cancer Institute Wayne St — Detroit, Michigan, United States
- University of Texas/MD Anderson Cancer Center MD Anderson 2 — Houston, Texas, United States
- Novartis Investigative Site — Montreal, Quebec, Canada
- Novartis Investigative Site — Villejuif, France
- Novartis Investigative Site — Essen, Germany
- Novartis Investigative Site — Milan, MI, Italy
- Novartis Investigative Site — Naples, Italy
- Novartis Investigative Site — Rotterdam, South Holland, Netherlands
- Novartis Investigative Site — Utrecht, Netherlands
- Novartis Investigative Site — Barcelona, Catalonia, Spain
- Novartis Investigative Site — Barcelona, Catalonia, Spain
- Novartis Investigative Site — L'Hospitalet de Llobregat, Catalonia, Spain
- Novartis Investigative Site — Valencia, Valencia, Spain
- Novartis Investigative Site — Madrid, Spain
- Novartis Investigative Site — Madrid, Spain
- Novartis Investigative Site — Madrid, Spain
Full record on ClinicalTrials.gov
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