First Time in Human Study of AZD8701 With or Without Durvalumab in Participants With Advanced Solid Tumours

Official Title

A Phase I First-in-Human Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD8701 Administered Intravenously as Monotherapy and in Combination With Durvaluamb (MEDI4736) in Participants With Advanced Solid Tumours.

Summary:

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumour Activity of AZD8701 Alone and in Combination with Durvalumab (MEDI4736) in Adult Subjects with Select Advanced Solid Tumours

Trial Description

Primary Outcome:

• Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of AEs and SAEs
• Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of Dose Limiting Toxicities (DLTs)
• Maximum Tolerated dose (or optimal dose or maximum feasible dose) and RP2D of AZD8701 as monotherapy and in combination with Durvalumab assessed through evaluation of vital signs and abnormal laboratory parameters
• Incidence of AEs and SAEs related to AZD8701 as monotherapy and in combination with Durvalumab in disease specific expansions treated at the MTD/OBD/MFD
• Objective Response Rate according to RECIST 1.1 by investigator assessment in disease specific expansions treated at the MTD/OB/MFD

Secondary Outcome:

• Progression-free survival according to RECIST 1.1 by investigator assessment
• Duration of Response according to RECIST 1.1 by investigator assessment
• Disease Control Rate at 16 weeks according to RECIST 1.1 by investigator assessment
• Time to Response according to RECIST 1.1 by investigator assessment
• Best percentage change in tumour size according to RECIST 1.1 by investigator assessment
• Overall Survival at 18 months
• Plasma AZD8701 and associated PK parameters when administered as monotherapy and in combination with Durvalumab
• Plasma and urine concentrations of AZD8701 and associated PK parameters when administered as monotherapy and in combination with Durvalumab
• Plasma and urine concentrations of AZD8701 and associated PK parameters when administered as monotherapy and in combination with Durvalumab
• Urine concentrations of AZD8701 to assess renal clearance when administered as monotherapy and in combination with Durvalumab
• Serum concentrations of Durvalumab and associated PK parameters when administered in combination with AZD8701
• Change in FOXP3 mRNA expression

This is a Phase I, First in Human, multicentre, open-label, multiple arm study with dose escalations and expansions at selected doses. Dose-escalation will occur with AZD8701 in monotherapy (Part 1) and in combination with durvalumab (Part 3) in selected participants with HNSCC, TNBC, NSCLC, ccRCC, gastric cancer, melanoma, cervical cancer, small-cell lung cancer and/or participants with solid tumours who have demonstrated a response to prior PD-(L)1 treatment. Disease specific expansions will occur with a selected dose AZD8701 in participants with NSCLC (Part 2) and with a selected dose of AZD8701 and durvalumab in participants with TNBC and clear cell RCC (Part 4).

View this trial on ClinicalTrials.gov