A Phase Ib Study of PDR001 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Study Overview
Brief Summary
A two part study to determine the maximum tolerated dose and/or recommended phase 2 dose of PDR001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in first line. There will be a dose escalation part and a dose expansion part.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed advanced (unresectable and/or metastatic) HCC
- •Patients with advanced HCC not amenable for surgical or loco-regional treatment
- •At least one measureable tumor lesion that that has not been previously locally
- •Patients with current cirrhotic status of Child-Pugh class A only (5-6 points with total bilirubin < 2 mg/dL for dose-escalation) with no encephalopathy and no clinical ascites (ascites controlled by diuretics is also excluded in this study).
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patient must meet required laboratory values at the screening
- •Normal electrocardiogram at screening
Exclusion Criteria
- •Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- •Invasion of the main portal vein and/or tumor involvement in more than 50% of the liver (applicable only for the dose-escalation part)
- •Patients with Portal-caval shunts
- •Prior or concomitant systemic anti-cancer treatment for advanced disease
- •Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
- •Cardiac or cardiac repolarization abnormality
- •Patients with active Hepatitis B infection (HBsAg positive) that are not receiving antiviral treatment are excluded
- •Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)
- •Loco-regional treatment within 4 weeks prior to initiation of study treatment.
Arms & Interventions
PDR001 + Sorafenib
PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses)
Intervention: PDR001 (Drug)
PDR001 + Sorafenib
PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses)
Intervention: Sorafenib (Drug)
Outcomes
Primary Outcomes
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From baseline until 30 days of last dose of study treatment
Incidence and severity of AEs and SAEs, including changes in laboratory vital signs and ECGs
Incidendence of Dose Limiting Toxicities (DLTs)
Time Frame: During the first 8 weeks of treatment
A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
Dose interruptions
Time Frame: Until end of treatment, assessed for a median time of 4 months
Tolerability measured by the number of subjects who have interruptions of study treatment
Dose reductions
Time Frame: Until end of treatment, assessed for a median time of 4 months
Tolerability measured by the number of subjects who have reductions of study treatment
Dose intensity
Time Frame: Until end of treatment, assessed for a median time of 4 months
Tolerability measured by the dose intensity of study treatment
Secondary Outcomes
- Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level(Until end of treatment, assessed for a median time of 4 months)
- PDR001 trough concentration(Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days)
- Maximum concentration (Cmax) of sorafenib(Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days)
- Time to reach maximum concentration (Tmax) of sorafenib(Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days)
- Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)(Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days)
- Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib(Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days)