Clinical trial NCT01938612: A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours
Official title: A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: MEDI4736
Advanced solid tumors
squamous cell carcinoma of the head and Neck
biliary tract cancer
squamous cell carcinoma of esophagus cancer
B7-H1
PD-L1
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-09-10
Enrollment: 269
Sex: ALL
Minimum age (years): 20
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs)
timeFrame: 90 days after the last dose of MEDI4736
Secondary outcomes:
measure: Area under the concentration of MEDI4736 time curve
timeFrame: Up to 90 days after the last dose of MEDI4736
measure: Percentage of participants who developed detectable anti-drug antibodies (ADAs).
timeFrame: Up to 6 months after the last dose of MEDI4736 or up to 1 month after the last dose of tremelimumab where applicable.
measure: Objective response rate (ORR)
timeFrame: From first dose of study drug until death or up to 2 years
measure: Maximum tolerated dose (MTD) or optimal biological dose (OBD)
timeFrame: 90 days after the last dose of MEDI4736
measure: Maximum concentration of MEDI4736
timeFrame: Up to 90 days after the last dose of MEDI4736
measure: Clearance
timeFrame: Up to 90 days after the last dose of MEDI4736
measure: half-life after administration of MEDI4736
timeFrame: Up to 90 days after the last dose of MEDI4736
measure: Disease control rate (DCR)
timeFrame: From first dose of study drug until death or up to 2 years
measure: Duration of response (DoR)
timeFrame: From first dose of study drug until death or up to 2 years
measure: Progression-free survival (PFS)
timeFrame: From first dose of study drug until death or up to 2 years
measure: Overall survival (OS)
timeFrame: From first dose of study drug until death or up to 2 years
Other outcomes:
Locations:
city: Beppu-shi
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kitaadachi-gun
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kure-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Robert Iannone, MD
role: STUDY_DIRECTOR
References:
citation: Doki Y, Ueno M, Hsu CH, Oh DY, Park K, Yamamoto N, Ioka T, Hara H, Hayama M, Nii M, Komuro K, Sugimoto M, Tahara M. Tolerability and efficacy of durvalumab, either as monotherapy or in combination with tremelimumab, in patients from Asia with advanced biliary tract, esophageal, or head-and-neck cancer. Cancer Med. 2022 Jul;11(13):2550-2560. doi: 10.1002/cam4.4593. Epub 2022 May 24.