A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours

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

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.

Anthony B. El-Khoueiry, Diansong Zhou, Mustafa Özgüroğlu, Melissa Johnson, Ghassan K. Abou‐Alfa et al. (9 authors)

Regular and Young Investigator Award Abstracts2022-11-01

10.1136/jitc-2022-sitc2022.0591

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

Yuichiro Doki, Makoto Ueno, Chih‐Hung Hsu, Do‐Youn Oh, Keunchil Park et al. (13 authors)

Cancer Medicine2022-05-2458 citations

10.1002/cam4.4593

Evaluation of safety and tolerability of durvalumab (D) with or without tremelimumab (T) in patients (pts) with biliary tract cancer (BTC).

Tatsuya Ioka, Makoto Ueno, Do‐Youn Oh, Yutaka Fujiwara, Jen‐Shi Chen et al. (15 authors)

Journal of Clinical Oncology2019-01-29111 citations

10.1200/jco.2019.37.4_suppl.387

Phase I study to evaluate the safety and tolerability of MEDI4736, an anti-programmed cell death ligand-1 (PD-L1) antibody, in Japanese patients with advanced solid tumors.

Haruo Iguchi, Naoyuki Nogami, Toshiyuki Kozuki, Toshihiko Matsumoto, Kenji Tamura et al. (11 authors)

Journal of Clinical Oncology2015-05-207 citations

10.1200/jco.2015.33.15_suppl.3039

Interventions

DRUGMEDI4736

MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.

DRUGtremelimumab

tremelimumab is administered by IV infusion every 4 weeks

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to 130 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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.
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.

Countries

Japan, South Korea, Taiwan

Outcome results

None listed