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

NCT ID: NCT01351103

Last Updated: 2025-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

185 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-01

Study Completion Date

2024-06-17

Brief Summary

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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.

Detailed Description

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This open-label multicenter phase 1 dose escalation study was the first to administer LGK974 as a single agent or in combination with PDR001 in humans.

The study comprised of 2 parts: a dose escalation of LGK974 as a single agent, followed by a safety expansion in specific disease indications; and a dose escalation of LGK974 in combination with PDR001, followed by a safety expansion in cutaneous melanoma.

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LGK974

LGK974

Group Type EXPERIMENTAL

LGK974

Intervention Type DRUG

LGK974 in combination with PDR001

LGK in combination with PDR001

Group Type EXPERIMENTAL

LGK974

Intervention Type DRUG

PDR001

Intervention Type BIOLOGICAL

Interventions

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LGK974

Intervention Type DRUG

PDR001

Intervention Type BIOLOGICAL

Other Intervention Names

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WNT974

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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UCLA School of Medicine

Los Angeles, California, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center Johns Hopkins

Baltimore, Maryland, United States

Site Status

Dana Farber Cancer Institute SC-7

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center Onc Dept.

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Institute Wayne St

Detroit, Michigan, United States

Site Status

University of Texas/MD Anderson Cancer Center MD Anderson 2

Houston, Texas, United States

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Villejuif, , France

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Napoli, , Italy

Site Status

Novartis Investigative Site

Rotterdam, South Holland, Netherlands

Site Status

Novartis Investigative Site

Utrecht, , Netherlands

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Countries

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United States Canada France Germany Italy Netherlands Spain

References

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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.

Reference Type DERIVED
PMID: 33941878 (View on PubMed)

Related Links

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Other Identifiers

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2011-000495-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLGK974X2101

Identifier Type: -

Identifier Source: org_study_id

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