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

Last Update: Dec 06, 2021

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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

The 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 that have progressed despite standard therapy or for which no effective standard therapy exists

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
Start date 
Dec 01, 2011
Completion date 
Nov 23, 2023
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:

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.

Exclusion Criteria:

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

Study Locations

United States
UCLA School of Medicine
Recruiting
Los Angeles, 90024 - California
Contact: Elizabeth O Laco (310-794-0738) - [email protected] - Antoni Ribas
United States
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins
Recruiting
Baltimore, 21287-0013 - Maryland
Contact: Christina Raynor (410-502-2377) - [email protected] - Patrick Forde
United States
Columbia University Medical Center
Recruiting
New York, 10032 - New York
Contact: Swathi Balaji (212-304-5548) - [email protected] - Richard Carvajal
United States
University of Texas/MD Anderson Cancer Center MD Anderson 2
Recruiting
Houston, 77030-4009 - Texas
Contact: Stepanek M. Vanda (713-792-2921) - [email protected] - Filip P. Janku
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
Hospitalet de LLobregat, 08907
Catalunya
Spain
Novartis Investigative Site
Recruiting
Valencia, 46010
Comunidad Valenciana
Spain
Novartis Investigative Site
Recruiting
Madrid, 28009
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28040
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28050
-
Spain

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

Have a question?

Call 1-888-669-6682 or email [email protected]