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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: MEDI4736; Drug: tremelimumab

• Study Type: Interventional
• Enrollment (Actual): 269
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Beppu-shi, Japan, 874-0011
    • Research Site
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Kitaadachi-gun, Japan, 362-0806
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Research Site
  • Kure-shi, Japan, 737-0023
    • Research Site
  • Matsuyama-shi, Japan, 791-0280
    • Research Site
  • Nagoya-shi, Japan, 464-8681
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Osakasayama, Japan, 589-8511
    • Research Site
  • Sapporo-shi, Japan, 003-0804
    • Research Site
  • Sapporo-shi, Japan, 060-8648
    • Research Site
  • Suita-shi, Japan, 565-0871
    • Research Site
  • Sunto-gun, Japan, 411-8777
    • Research Site
  • Takatsuki-shi, Japan, 569-8686
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site
• Taiwan
  • Tainan, Taiwan, 704
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 126 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI4736 Q2W; Evaluate MEDI4736 given every 2 weeks	Drug: MEDI4736; MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 Q3W; Evaluate MEDI4736 given every 3 weeks	Drug: MEDI4736; MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 Dose Expansion; evaluate MEDI4736 given every 2 weeks	Drug: MEDI4736; MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 Q4W; Evaluate MEDI4736 given every 4 weeks	Drug: MEDI4736; MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 combined with another drug; evaluate MEDI4736 in combination with another drug given every 4 weeks	Drug: tremelimumab; tremelimumab is administered by IV infusion every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs)	Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.	90 days after the last dose of MEDI4736

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration of MEDI4736 time curve	If data allow, noncompartmental PK parameter (AUC) will be estimated.	Up to 90 days after the last dose of MEDI4736
Percentage of participants who developed detectable anti-drug antibodies (ADAs).	The immunogenic potential of MEDI4736 or tremelimumab will be assessed by summarizing the number percentage of subjects who develop 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.
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)	maximum tolerated dose (MTD) or optimal biological dose (OBD) of MEDI4736, if possible	90 days after the last dose of MEDI4736
Maximum concentration of MEDI4736	If data allow, noncompartmental PK parameter (Cmax) will be estimated.	Up to 90 days after the last dose of MEDI4736
Clearance	If data allow, noncompartmental PK parameter (CL) will be estimated.	Up to 90 days after the last dose of MEDI4736
half-life after administration of MEDI4736	If data allow, noncompartmental PK parameter (t½) will be estimated.	Up to 90 days after the last dose of MEDI4736
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)	Alive and progression free at 6 months (APF6) and 12 months (APF12) will be obtained using the Kaplan-Meier plot of PFS.	From first dose of study drug until death or up to 2 years
Overall survival (OS)	The proportion of patients alive at 12 months will be obtained from the Kaplan-Meier plot of OS.	From first dose of study drug until death or up to 2 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Robert Iannone, MD, AstraZeneca

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2013
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): November 25, 2020

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 5, 2013
• First Posted (Estimate): September 10, 2013

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: PD-L1; biliary tract cancer; MEDI4736; Advanced solid tumors; squamous cell carcinoma of the head and Neck; squamous cell carcinoma of esophagus cancer; B7-H1
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab
• Other Study ID Numbers: D4190C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.