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
2 other identifiers
interventional
185
7 countries
20
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 pancreatic-cancer
Started Dec 2011
Longer than P75 for phase_1 pancreatic-cancer
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 4, 2011
CompletedFirst Posted
Study publicly available on registry
May 10, 2011
CompletedStudy Start
First participant enrolled
December 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 17, 2024
CompletedJune 13, 2025
June 1, 2025
9.5 years
May 4, 2011
June 10, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of dose limiting toxicities (DLTs) during the first cycle of LGK974 treatment and during the first 2 cycles of LGK974 in combination with PDR001
DLT is defined as an adverse event or abnormal laboratory value that is assessed by the investigator as unrelated to disease, disease progression, intercurrent illness, or concomitant medications and that meets the criteria defined in the study protocol. The objective was to determine the Maximum Tolerated Dose (MTD) or Recommended Dose for Expansion (RDE) of LGK974 as a single agent and in combination with PDR001 when administered orally to adult patients with malignancies dependent on Wnt ligands.
28 days (LGK974 single agent) and 56 days (LGK974 in combination with PDR001)
Secondary Outcomes (5)
Type and category of study drug related adverse events (AE)
61 months
Absorption and plasma concentrations of LGK974
61 months
PD related to the Wnt pathway
61 months
Overall response rate of tumor
61 months
Absorportion and plasma concentrations of PDR001
61 months
Study Arms (2)
LGK974
EXPERIMENTALLGK974
LGK974 in combination with PDR001
EXPERIMENTALLGK in combination with PDR001
Interventions
Eligibility Criteria
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
UCLA School of Medicine
Los Angeles, California, 90024, United States
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins
Baltimore, Maryland, 21287-0013, United States
Dana Farber Cancer Institute SC-7
Boston, Massachusetts, 02215, United States
University of Michigan Comprehensive Cancer Center Onc Dept.
Ann Arbor, Michigan, 48109-0944, United States
Karmanos Cancer Institute Wayne St
Detroit, Michigan, 48201, United States
University of Texas/MD Anderson Cancer Center MD Anderson 2
Houston, Texas, 77030-4009, United States
Novartis Investigative Site
Montreal, Quebec, H2W 1T8, Canada
Novartis Investigative Site
Villejuif, 94800, France
Novartis Investigative Site
Essen, 45147, Germany
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Napoli, 80131, Italy
Novartis Investigative Site
Rotterdam, South Holland, 3015 GD, Netherlands
Novartis Investigative Site
Utrecht, 3584CX, Netherlands
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08036, Spain
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907, Spain
Novartis Investigative Site
Valencia, Valencia, 46010, Spain
Novartis Investigative Site
Madrid, 28009, Spain
Novartis Investigative Site
Madrid, 28040, Spain
Novartis Investigative Site
Madrid, 28050, Spain
Related Publications (1)
Rodon J, Argiles G, Connolly RM, Vaishampayan U, de Jonge M, Garralda E, Giannakis M, Smith DC, Dobson JR, McLaughlin ME, Seroutou A, Ji Y, Morawiak J, Moody SE, Janku F. Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours. Br J Cancer. 2021 Jul;125(1):28-37. doi: 10.1038/s41416-021-01389-8. Epub 2021 May 3.
PMID: 33941878DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2011
First Posted
May 10, 2011
Study Start
December 1, 2011
Primary Completion
June 1, 2021
Study Completion
June 17, 2024
Last Updated
June 13, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share