A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours
- Registration Number
- NCT01938612
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a phase I, open-label, multicentre study of MEDI4736 administered intravenously with a standard 3+3 dose-escalation phase to evaluate safety, tolerability, and pharmacokinetics in patients with advanced solid tumor followed by an expansion phase in patients with advanced solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 269
- In the dose-escalation phase: patients with advanced solid tumors refractory to standard treatment, intolerant of standard treatment, or for which no standard therapy exists.
In the dose-expansion phase: histologically- or cytologically-confirmed advanced or metastatic biliary tract cancer (BTC), esophagus cancer(EC) (squamous cell carcinoma) or squamous cell carcinoma of the head and neck (SCCHN). - men or women. - Eastern Cooperative Oncology Group (ECOG) status of 0 or 1. - Adequate organ and marrow function. - Subjects must have at least 1 measurable lesion. - Available archived tumor tissue sample. - Willingness to provide consent for biopsy samples.
- Any prior Grade ≥ 3 irAE while receiving immunotherapy - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody - Active or prior documented autoimmune disease within the past 2 years - History of primary immunodeficiency - Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment - Women who are pregnant or lactating - Uncontrolled intercurrent illness - Known history of tuberculosis - Known to be human immunodeficiency virus (HIV) positive - Hepatitis B or C infection - Other invasive malignancy within 5 years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MEDI4736 Q2W MEDI4736 Evaluate MEDI4736 given every 2 weeks MEDI4736 Dose Expansion MEDI4736 evaluate MEDI4736 given every 2 weeks MEDI4736 Q4W MEDI4736 Evaluate MEDI4736 given every 4 weeks MEDI4736 combined with another drug tremelimumab evaluate MEDI4736 in combination with another drug given every 4 weeks MEDI4736 Q3W MEDI4736 Evaluate MEDI4736 given every 3 weeks
- Primary Outcome Measures
Name Time Method Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs) 90 days after the last dose of MEDI4736 Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.
- Secondary Outcome Measures
Name Time Method Area under the concentration of MEDI4736 time curve Up to 90 days after the last dose of MEDI4736 If data allow, noncompartmental PK parameter (AUC) will be estimated.
Percentage of participants who developed detectable anti-drug antibodies (ADAs). Up to 6 months after the last dose of MEDI4736 or up to 1 month after the last dose of tremelimumab where applicable. The immunogenic potential of MEDI4736 or tremelimumab will be assessed by summarizing the number percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Objective response rate (ORR) From first dose of study drug until death or up to 2 years Maximum tolerated dose (MTD) or optimal biological dose (OBD) 90 days after the last dose of MEDI4736 maximum tolerated dose (MTD) or optimal biological dose (OBD) of MEDI4736, if possible
Maximum concentration of MEDI4736 Up to 90 days after the last dose of MEDI4736 If data allow, noncompartmental PK parameter (Cmax) will be estimated.
Clearance Up to 90 days after the last dose of MEDI4736 If data allow, noncompartmental PK parameter (CL) will be estimated.
half-life after administration of MEDI4736 Up to 90 days after the last dose of MEDI4736 If data allow, noncompartmental PK parameter (t½) will be estimated.
Disease control rate (DCR) From first dose of study drug until death or up to 2 years Duration of response (DoR) From first dose of study drug until death or up to 2 years Progression-free survival (PFS) From first dose of study drug until death or up to 2 years Alive and progression free at 6 months (APF6) and 12 months (APF12) will be obtained using the Kaplan-Meier plot of PFS.
Overall survival (OS) From first dose of study drug until death or up to 2 years The proportion of patients alive at 12 months will be obtained from the Kaplan-Meier plot of OS.
Trial Locations
- Locations (1)
Research Site
🇨🇳Taoyuan, Taiwan