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

Who is this study for? Adult patients with Locally Advanced or Metastatic B-RAF Mutant Colorectal, Pancreatic Adenocarcinoma, Melanoma, Lung Small-Cell Carcinoma, and Head and Neck Squamous Cell Carcinoma
What treatments are being studied? LGK974
Status: Recruiting
Location: See all (22) locations...
Intervention Type: Biological, Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

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

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
View:

• 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.

Locations
United States
California
UCLA School of Medicine
Recruiting
Los Angeles
Massachusetts
Dana Farber Cancer Institute SC
Withdrawn
Boston
Dana Farber Cancer Institute SC-7
Completed
Boston
Maryland
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins
Recruiting
Baltimore
Michigan
University of Michigan Comprehensive Cancer Center Onc Dept.
Completed
Ann Arbor
Karmanos Cancer Institute Wayne St
Completed
Detroit
New York
Columbia University Medical Center
Recruiting
New York
Texas
University of Texas/MD Anderson Cancer Center MD Anderson 2
Recruiting
Houston
Other Locations
Canada
Novartis Investigative Site
Recruiting
Montreal
France
Novartis Investigative Site
Recruiting
Villejuif Cedex
Germany
Novartis Investigative Site
Recruiting
Essen
Italy
Novartis Investigative Site
Recruiting
Milano
Novartis Investigative Site
Recruiting
Napoli
Netherlands
Novartis Investigative Site
Recruiting
Rotterdam
Novartis Investigative Site
Recruiting
Utrecht
Spain
Novartis Investigative Site
Recruiting
Barcelona
Novartis Investigative Site
Recruiting
Barcelona
Novartis Investigative Site
Recruiting
Hospitalet De Llobregat
Novartis Investigative Site
Recruiting
Madrid
Novartis Investigative Site
Recruiting
Madrid
Novartis Investigative Site
Recruiting
Madrid
Novartis Investigative Site
Recruiting
Valencia
Contact Information
Primary
Novartis Pharmaceuticals
Novartis.email@novartis.com
1-888-669-6682
Backup
Novartis Pharmaceuticals
+41613241111
Time Frame
Start Date: December 1, 2011
Estimated Completion Date: November 23, 2023
Participants
Target number of participants: 185
Treatments
Experimental: LGK974
LGK974
Experimental: LGK974 in combination with PDR001
LGK in combination with PDR001
Authors
Filip P. Janku, Ulka A. Vaishampayan, Patrick Forde, Misako Nagasaka, Marios Giannakis, Andrew P. Wolanski, Antoni Ribas, Roisin Connolly, Richard Carvajal, David Smith
Sponsors
Leads: Novartis Pharmaceuticals

This content was sourced from clinicaltrials.gov