NCT03101839

Phase I Dose-Escalation Study of AZD4785 in Patients With Advanced Solid Tumours

A Phase I, Open-Label, Multicentre Dose-Escalation Study to Investigate the Safety and Pharmacokinetics of AZD4785 in Patients With Advanced Solid Tumours Where KRAS May Be an Important Driver of Tumour Survival

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

Summary

A Phase I, open-label, multicentre, dose-escalation study to investigate the safety, pharmacokinetics and maximum tolerated dose (MTD) of AZD4785 in patients with advanced solid tumours where KRAS may be an important driver of tumour survival. Part A: Dose escalation in patients with solid tumours to evaluate safety, pharmacokinetics and maximum tolerated dose (MTD). Once the maximum tolerated dose (MTD) is established, a dose expansion cohort may be included in Part A, with up to an additional 6 patients to further explore the PK, safety, tolerability, and preliminary anti-tumour activity of the AZD4785 MTD for confirmation of the recommended phase 2 dose (RP2D). Part B: Expansion cohort at the selected dose in patients with non-small cell lung cancer (NSCLC) to evaluate PK parameters, safety, tolerability, and preliminary anti-tumour activity of the AZD4785 RP2D as monotherapy in patients with NSCLC. Approximately 20 patients with NSCLC (Two groups of approximately 10 patients each) with NSCLC will be enrolled to Part B. Group 1 patients will have an option to provide tumour biopsies and Group 2 will be required (mandatory) to provide paired tumour biopsies. Overall up to 12 patients in Group 2Part B patients will be required (mandatory) to may provide paired tumour biopsies. A third group of up to 20 patients with other tumour types and/or a potential different schedule may be added based on the results seen in Parts A and B and any other emerging data and may also provide biopsies.

Detailed description

This is a First-Time-in-Human (FTIH), Phase 1 study to determine the MTD, recommended Phase 2 dose (RP2D), safety, tolerability, pharmacodynamics, and pharmacokinetics of AZD4785. The study will be conducted in two parts: a dose-escalation phase (Part A)and an expansion phase (Part B). A third group of up to 20 patients with other tumour types and/or a potential different schedule may be added based on the results seen in Parts A and B and any other emerging data. AZD4785 will be given as an IV infusion over 1 hour, initially in 3 loading doses during the first week and then weekly thereafter. The loading doses will be given on Days 1, 3, and 5 of the first week and weekly thereafter on Days 8, 15, and 22 of 28 Day cycles. In subsequent cycles AZD4785 will be administered on Days 1, 8, 15, and 22 until disease progression, intolerable toxicity, or discontinuation criteria have been met. Once the MTD is established, a dose expansion cohort may be included in Part A, with up to 6 additional patients to explore the PK, safety, tolerability, and preliminary anti-tumour activity of the AZD4785 MTD for confirmation of the RP2D. Thereafter, Part B expansion phase will continue to explore PK parameters, safety, tolerability, and preliminary anti-tumour activity of the AZD4785 RP2D as monotherapy in patients with NSCLC. Approximately 20 patients with NSCLC (2 groups of approximately 10 patients each) with NSCLC will be enrolled to Part B. Group 1 patients will have an option to provide tumour biopsies and Group 2 will be required (mandatory) to provide paired tumour biopsies. Overall up to 12 patients in Part B may provide paired tumour biopsies. A third group of up to 20 patients with other tumour types and/or a potential different schedule may be added based on the results seen in Parts A and B and any other emerging data and may also provide biopsies. Up to 12 patients in Part B may provide paired biopsies.

Conditions

• Non-Small Cell Lung Cancer
• Advanced Solid Tumours

Interventions

Type	Name	Description
DRUG	AZD4785	KRAS Antisense Oligonucleotide

Timeline

• Start date: 2017-05-15
• Primary completion: 2019-01-08
• Completion: 2019-01-08
• First posted: 2017-04-05
• Last updated: 2019-10-04

Locations

5 sites across 2 countries: United States, United Kingdom

Regulatory

• FDA-regulated drug study