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

Study 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.

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedLGK974 and PDR001

The study team can explain what participation involves.

Who it may be forBRAF

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Jun 13, 2025 · Source: ClinicalTrials.gov

Is enrollment open?Completed

Ask the study team to confirm whether enrollment is open.

What kind of study?Phase 1

Interventional

Where is it offered?20 U.S. locations

Locations may change over time.

Who runs it?Novartis Pharmaceuticals

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 1
Sponsor: Novartis Pharmaceuticals
Interventions being studied: Drug: LGK974; Biological: PDR001

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Biomarkers

BRAF→

Public criteria

Who may be able to participate

The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.

Requirements people may need to meetInclusion 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.

Reasons someone may not be able to joinExclusion 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/

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

UCLA School of MedicineLos Angeles, California
Sidney Kimmel Comprehensive Cancer Center Johns HopkinsBaltimore, Maryland
Dana Farber Cancer Institute SC-7Boston, Massachusetts
University of Michigan Comprehensive Cancer Center Onc Dept.Ann Arbor, Michigan
Karmanos Cancer Institute Wayne StDetroit, Michigan
University of Texas/MD Anderson Cancer Center MD Anderson 2Houston, Texas
Novartis Investigative SiteMontreal, Quebec
Novartis Investigative SiteVillejuif
Novartis Investigative SiteEssen
Novartis Investigative SiteMilan, MI
Novartis Investigative SiteNaples
Novartis Investigative SiteRotterdam, South Holland

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Jun 13, 2025. Always confirm current availability with the study team.

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