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

A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands

ClinicalTrials.gov Identifier: NCT01351103

Novartis Reference Number: CLGK974X2101

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
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
Phase 
Phase 1
Overall status 
Recruiting
Enrollment count 
184 participants
Start date 
Dec 01, 2011
Completion date 
Mar 25, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
LGK974
Biological
PDR001

Eligibility 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

Study Locations

United States
UCLA School of Medicine
Recruiting
Los Angeles, 90024
California
United States
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins
Recruiting
Baltimore, 21287-0013
Maryland
United States
Dana Farber Cancer Institute SC
Withdrawn
Boston, 02115
Massachusetts
United States
Dana Farber Cancer Institute SC-7
Recruiting
Boston, 02215
Massachusetts
United States
University of Michigan Comprehensive Cancer Center Onc Dept.
Completed
Ann Arbor, 48109-0944
Michigan
United States
Karmanos Cancer Institute Wayne St
Recruiting
Detroit, 48201
Michigan
United States
University of Texas/MD Anderson Cancer Center MD Anderson 2
Recruiting
Houston, 77030-4009
Texas
United States
Netherlands
Novartis Investigative Site
Recruiting
Rotterdam, 3075 EA
-
Netherlands
Novartis Investigative Site
Recruiting
Utrecht, 3584CX
-
Netherlands
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
Recruiting
Madrid, 28009
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28050
-
Spain

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]