Phase Ib/II Study of INC280 + PDR001 or PDR001 Single Agent in Advanced HCC

• Status: Completed
• Trial end date: 2021-06-24
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study of INC280 and PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent or in combination with INC280 administered orally in adult patients with advanced hepatocellular carcinoma (HCC).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Spartalizumab

Criteria

Inclusion Criteria:

1. Histologically or cytologically documented locally advanced recurrent or metastatic HCC or for patients with cirrhosis according to the American Association for the Study of Liver Diseases (AASLD) and Asian Pacific Association for the study of the liver (APASL) criteria. Current cirrhotic status of Child Pugh Class A (5-6 points), with no encephalopathy and/or clinically significant ascites (defined as requiring the use of diuretics or paracentesis treatment).

2. Patients must have received prior systemic sorafenib treatment for HCC with documented progression during or after discontinuation of sorafenib treatment (for France only: patients must have received at least 8 weeks of prior sorafenib treatment), or are intolerant to sorafenib (defined as documented Grade 3 or 4 adverse events that led to sorafenib discontinuation),.

3. ECOG Performance Status ≤ 1.

4. Willing and able to swallow and retain oral medication. Other protocol defined Inclusion criteria may apply.

Exclusion Criteria:

1. Use of any live vaccines within 4 weeks of initiation of study treatment.

2. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).

3. Clinically significant pleural effusion that either required pleurocentesis or is associated with shortness of breath.

4. Active autoimmune disease or a documented history of autoimmune disease.

5. Clinically significant, uncontrolled heart diseases.

6. Patient having out of range laboratory values defined as:

• Total bilirubin > 2 mg/dL, 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) > 5 x ULN

• Aspartate aminotransferase (AST) > 5 x ULN

• Coagulation: Prothrombin Time (PT) > 4 seconds more than the ULN or International Normalized Ratio (INR) > 1.7

• Absolute neutrophil count (ANC) < 1.5 x 109/L

• Platelet count < 75 x 109/L

• Hemoglobin < 9 g/dL

• Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 45 mL/min

• Asymptomatic serum amylase grade > 2 (1.5-2.0 x ULN). Patients with grade 1 or grade 2 serum amylase at the beginning of the study must be confirmed to have no signs or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)

• Serum lipase > ULN

• Potassium, Magnesium, Phosphorus, total Calcium (corrected for serum albumin) outside of normal limits (patients may be enrolled if corrected to within normal limits with supplements during screening)

Other protocol-defined Exclusion criteria may apply.