NCT01975831

A Phase 1 Study to Evaluate MEDI4736 in Combination With Tremelimumab

A Phase 1 Study to Evaluate the Safety and Tolerability of Anti-PD-L1, MEDI4736, in Combination With Tremelimumab in Subjects With Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 104 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a Phase 1, open-label, nonrandomized, multicenter study of durvalumab and tremelimumab in subjects with advanced cancers who were not eligible for, declined, or failed standard treatment. The primary study objective was to determine the maximum tolerated dose (MTD) and safety profile of the durvalumab and tremelimumab combination. Secondary objectives were to evaluate the pharmacokinetics (PK) and immunogenicity of durvalumab and tremelimumab, and the antitumor activity (tumor response, progression-free survival \[PFS\], and overall survival \[OS\]) of the durvalumab and tremelimumab combination. (Note: Collection of PK and immunogenicity samples was removed by amendment; analysis was not done.) Exploratory objectives were to evaluate the biological activity of the durvalumab and tremelimumab combination.

Detailed description

The study comprised a 3 + 3 dose escalation phase in which 3 to 6 subjects were enrolled into sequential cohorts until determination of the MTD, followed by an expansion phase in 5 tumor type-specific cohorts (i.e., ovarian cancer, colorectal cancer, non-triple negative breast cancer, renal cell carcinoma, and cervical cancer). Each expansion cohort was to include 15 subjects treated with the identified MTD or maximum dose tested in the dose-escalation phase. Subjects received durvalumab and tremelimumab over 12 to 13 four-week cycles during the Core Study, with continuous monitoring for safety, clinical efficacy, and biological activity, followed by optional treatment extension with durvalumab for subjects maintaining at least stable disease if agreed upon by the Investigator and Sponsor. After study treatment completion, study assessments were continued for up to 90 days after the last administration of study treatment or until start of alternate therapy, with long-term follow up after study completion for clinical outcomes at least every 6 months for up to 3 years following initiation of treatment. Study treatment in the Core Study continued for up to 12 months or until confirmed progressive disease (PD), initiation of alternative cancer therapy, observation of unacceptable toxicity, or any other criteria for treatment discontinuation. Optional treatment extension beyond the Core Study was permitted for subjects who completed the Core Study with a tumor response of stable disease or better and upon agreement by the Sponsor and Investigator. Extended treatment comprised durvalumab monotherapy administered at the recommended fixed dose of 1500 mg administered every 4 weeks (Q4W).

Conditions

• Breast Cancer
• Ovarian Cancer
• Colorectal Cancer
• Cervical Cancer
• Renal Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Durvalumab	Durvalumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes.
DRUG	Tremelimumab	Tremelimumab was administered as an intravenous (IV) infusion over 60 (± 5) minutes.

Timeline

• Start date: 2013-12-19
• Primary completion: 2019-12-01
• Completion: 2021-07-02
• First posted: 2013-11-05
• Last updated: 2022-10-12
• Results posted: 2020-06-22

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study