Groupe d'Etude en Oncologie du Quebec

Titre	A Phase I, Open-label, Dose Escalation Study of Oral LGK974 in Patients With Malignancies Dependent on Wnt Ligands
Protocole ID	CLGK974X2101
ClinicalTrials.gov ID	NCT01351103
Type(s) de cancer	Tumeurs solides
Phase	Phase I
Type étude	Clinique
Médicament	LGK974
Institution	CENTRE HOSPITALIER DE L'UNIVERSITE DE MONTREAL
Ville	Montréal
Investigateur(trice) principal(e)	Dre Rahima Jamal
Coordonnateur(trice)	Adeline Hamon 514-890-8000 poste 30737
Statut	Actif en recrutement
Date d'activation	24-08-2022
Critètes d'éligibilité	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.
Critètes d'exclusion	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

Groupe d'étude en oncologie du Québec