Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors.

Korábbi kezelés

• Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with treated brain metastases should be neurologically stable for at least 4 weeks prior to study entry and off steroids for at least 2 weeks before administration of any study treatment.

Más betegség

• History of severe hypersensitivity reactions to any ingredient of study drug(s) or other mAbs and/or their excipients.

Laborértékek

• Patient with out of range laboratory values defined as:
  • Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40 mL/min
  • Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
  • Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if ALT > 5 x ULN
  • Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor involvement of the liver, who are excluded if AST > 5 x ULN
  • Absolute neutrophil count (ANC) < 1.0 x 109/L
  • Platelet count < 75 x 109/L (growth factor or transfusion support may not be used to meet entry criterion)
  • Hemoglobin (Hgb) < 8 g/dL (growth factor or transfusion support may not be used to meet entry criterion)
  • Magnesium, calcium or phosphate abnormality CTCAE > grade 1
  • Potassium abnormality CTCAE ≥ grade 1; supplementation to meet eligibility criteria is acceptable
• Clinically significant cardiac disease or impaired cardiac function, including any of the following:
  • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia
  • On screening: QTcF > 450 msec (male), or > 460 msec (female)
  • QTc not assessable
  • Congenital long QT syndrome
  • History of familial long QT syndrome or known family history of as Torsades de Pointes
  • Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry

• Signed informed consent must be obtained prior to participation in the study.
• Patients must be ≥18 years of age at the time of informed consent form (ICF) signature.
• Patients with advanced/metastatic cancer who have progressed despite having received standard therapy in the metastatic setting or are intolerant to standard therapy, and for whom no effective standard therapy is available
• In expansion: patient with measurable disease as determined by RECIST version 1.1,
• Dose escalation, patients must fit into one of the following groups:
  • NSCLC, previously treated with an anti-PD-1/PD-L1 therapy
  • Cutaneous Melanoma, previously treated with an anti-PD-1/PD-L1 therapy
  • NPC
  • Dose expansion part, patients must fit into one of the following groups:
  • NSCLC with historic documentation of PD-L1 ≥ 1%. Patients must have progressive disease after having experienced at least 4 months of investigator-assessed disease stability or response on prior anti-PD-L1-containing therapy
  • Cutaneous Melanoma, previously treated with anit-PD-1/PD-L1 therapy. Patients should have documented progression following anti-PD-1/PD-L1 therapy.
  • NPC, naive to anti-PD-1/PD-L1 therapy
  • mssCRC, naive to anti-PD-1/PD-L1 therapy
  • TNBC, naive to anti-PD-1/PD-L1 therapy
• ECOG Performance Status ≤ 1
• Patients must have a site of disease amenable to core needle biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at baseline, and during therapy on the study. Exceptions may be considered after documented discussion with Novartis.