A Phase 1b Study of MEDI4736 in Combination With Tremelimumab in Subjects With Advanced Non-small Cell Lung Cancer

Phase 1

Completed

• Conditions: NSCLC; Non-small Cell Lung Cancer; Lung Cancer
• Interventions: Drug: MEDI4736; Drug: tremelimumab

• Registration Number: NCT02000947
• Lead Sponsor: MedImmune LLC

Brief Summary

The purpose of this study is to determine if MEDI4736 will be adequately tolerated in combination with tremelimumab in subjects with advanced non-small cell lung cancer (NSCLC).

Detailed Description

This is a multicenter, open-label, dose-escalation, and dose expansion study of MEDI4736 in combination with tremelimumab to evaluate the safety, tolerability, pharmacokinetic (PK), immunogenicity, and antitumor activity of MEDI4736 in combination with tremelimumab in adult subjects with advanced NSCLC.

Study Timeline

• Study Start: 2013-10-25
• Study First Submitted: 2013-11-27
• Study First Submitted QC: 2013-11-27
• Study First Posted: 2013-12-04
• Primary Completion: 2019-09-17
• Study Completion: 2019-09-17
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-29
• Last Update Posted: 2019-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 459

Inclusion Criteria

1. Age ≥ 18 years
2. Advanced non-small cell lung cancer
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
4. Adequate organ and marrow function

Exclusion Criteria

1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs
3. Active or prior documented autoimmune disease within the last 2 years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose Escalation	MEDI4736	MEDI4736 and tremelimumab received by intravenous infusion.
Dose Escalation	tremelimumab	MEDI4736 and tremelimumab received by intravenous infusion.
Arm C	tremelimumab	MEDI4736 and tremelimumab received by intravenous infursion
Arm A	MEDI4736	Medi4736 and tremelimumab received by intravenous infusion
Arm B	MEDI4736	MEDI4736 and tremelimumab received by intravenous infusion
Arm C	MEDI4736	MEDI4736 and tremelimumab received by intravenous infursion
Arm A	tremelimumab	Medi4736 and tremelimumab received by intravenous infusion
Arm B	tremelimumab	MEDI4736 and tremelimumab received by intravenous infusion

Primary Outcome Measures

Name	Time	Method
Objective response	At least 24 weeks as compared to baseline	Best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as defined as the best response among all overall responses recorded from the start of treatment until progression, or the last evaluable disease assessment in the absence of progressive disease (PD) prior to the initiation of subsequent anti-cancer therapy, or discontinuation from the study, whichever occurs first.
Number of subjects experiencing dose-limiting toxicities (DLTs)	Depending upon the cohort, the DLT evaluation period is from the 1st dose of study medication until (1) the 3rd dose of MEDI4736 and tremelimumab (2) the 2nd dose of MEDI4736 and tremelimumab or (3) the 3rd dose of MEDI4736 and 2nd dose of tremelimumab	The maximum tolerated dose (MTD), which is the highest dose within a cohort where no more than 1 out of 6 subjects experience DLTs or the highest protocol-defined dose for each agent in the absence of exceeding the MTD, will be evaluated using the following safety assessments: adverse events, serious advents, laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. Measurements will be aggregated to determine whether a subject has experienced a DLT as assessed by the investigator.
Number of subjects reporting adverse events	Screening through 90 days after the last dose of study medication	The number of subjects reporting adverse events (AEs) and number (percentage) of subjects reporting serious adverse events (SAEs) as graded by CTCAE Version 4.03

Secondary Outcome Measures

Name	Time	Method
Immunogenicity of tremelimumab in combination with MEDI4736	During treatment through study completion, about 2 years	Immunogenicity of MEDI4736 and tremelimumab will include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Antitumor activity of tremelimumab in combination with MEDI4736	During treatment through study completion, about 2 years	Antitumor activity will include objective response (OR) and disease control (DC) based on RECIST Version 1.1, duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
Pharmacokinetic parameters	During treatment through study completion, about 2 years	Assessment of PK of MEDI4736 and tremelimumab will include individual MEDI4736 and tremelimumab concentrations in serum, and PK parameters including peak concentration (Cmax), area under the concentration-time curve (AUC), clearance (CL), and half-life (t½).
Number of subjects reporting adverse events	Screening through 90 days after the last dose of study medication	The number of subjects reporting adverse events (AEs) and number (percentage) of subjects reporting serious adverse events (SAEs) as graded by CTCAE Version 4.03

Trial Locations

Locations (1)

Research Site; 🇬🇧 Manchester, United Kingdom