An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.

Phase 3

Completed

• Conditions: Advanced Solid Malignancies
• Interventions: Biological: MEDI4736 (Durvalumab); Biological: MEDI4736 (Durvalumab) + Tremelimumab

• Registration Number: NCT03084471
• Lead Sponsor: AstraZeneca

Brief Summary

To evaluate the safety, tolerability, and anti-tumor activity of the combination of durvalumab + tremelimumab or durvalumab alone in different solid tumors.

Detailed Description

This is an open-label, multi-center, study to determine the short and long term safety of fixed doses of durvalumab 1500 mg + tremelimumab 75 mg combination therapy or durvalumab 1500 mg monotherapy in patients with advanced solid malignancies. This study is modular in design, one or more of the modules will be opened in a given country / region based on local patient population prevalence, and results of feasibility studies. The total number of patients to be enrolled overall and in each module will depend on the types and number of tumor modules added to the main study and country-specific ancillary studies. The number of patients and sites to be involved in individual countries will be dependent on each module or ancillary study. This study consisted of a screening period, a treatment period, a 90 day safety follow-up period and a survival follow-up period. Patients will receive the investigation product (IP) via intravenous (IV) infusion once every 4 weeks (Q4W) in combination therapy or monotherapy as mentioned below - Combination therapy: Durvalumab 1,500 mg + tremelimumab 75 mg on Week 0, for up to a maximum of 4 doses (or cycles) followed by durvalumab 1,500 mg starting 4 weeks after the last infusion of the combination or discontinuation of tremelimumab.

Monotherapy: Durvalumab 1,500 mg on week 0.

Patients will attend a safety follow-up visit 90 days after study treatment discontinuation. Thereafter, patients will be contacted by phone or electronic communication every 3 months for survival status up to 5 years following date of first patient treatment initiation. All patients will be followed for a minimum of 6 months following enrolment of last patient. It is anticipated that the total enrolment period for the overall study will be approximately 2 to 3 years, with an overall duration of approximately 5 years

Study Timeline

• Study First Submitted: 2017-03-07
• Study First Submitted QC: 2017-03-20
• Study First Posted: 2017-03-21
• Study Start: 2017-06-05
• Primary Completion: 2020-03-31
• Results First Submitted: 2021-03-22
• Results First Submitted QC: 2021-05-20
• Results First Posted: 2021-06-15
• Status Verified: 2022-12
• Study Completion: 2022-12-16
• Last Update Submitted: 2022-12-21
• Last Update Posted: 2022-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 867

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Monotherapy	MEDI4736 (Durvalumab)	Monotherapy (Durvalumab 1,500 mg): Patients will receive durvalumab 1,500 mg via IV infusion Q4W on Week 0.
Combination therapy	MEDI4736 (Durvalumab)	Combination therapy (durvalumab + tremelimumab) : Patients will receive the combination therapy followed by monotherapy via intravenous (IV) infusion once Q4W: * Durvalumab 1,500 mg + tremelimumab 75 mg on Week 0, for up to a maximum of 4 doses (or cycles) and * Durvalumab 1,500 mg starting 4 weeks after the last infusion of the combination or discontinuation of tremelimumab.
Combination therapy	MEDI4736 (Durvalumab) + Tremelimumab	Combination therapy (durvalumab + tremelimumab) : Patients will receive the combination therapy followed by monotherapy via intravenous (IV) infusion once Q4W: * Durvalumab 1,500 mg + tremelimumab 75 mg on Week 0, for up to a maximum of 4 doses (or cycles) and * Durvalumab 1,500 mg starting 4 weeks after the last infusion of the combination or discontinuation of tremelimumab.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events of Special Interest (AESIs)	From screening to safety follow up visit (90 days after last dose), up to approximately 3 years.	Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of AESIs were assessed. AESIs included events with a potential inflammatory or immune-mediated mechanism that required interventions such as steroids, immunosuppressants, and/or hormone replacement therapy.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From screening to final data cutoff (maximum up to 4 years) following date of first patient treatment initiation.	Overall survival was defined as the time from the first date of treatment until death due to any cause.
Number of Participants With Adverse Events	From screening to safety follow up visit (90 days after last dose), maximum up to 4 years.	Incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of treatment-emergent AEs (including SAEs) will be assessed

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sheffield, United Kingdom