A Phase I, Multicenter, Open-label, First-in-Human, Dose Escalation and Expansion Study of AZD9592 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumors

JRCT ID: jRCT2031230002

Registered date:02/04/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced Solid Tumours, Carcinoma Non-small Cell Lung, Head and Neck Neoplasms
• Date of first enrollment: 02/04/2023
• Target sample size: 417
• Countries of recruitment: US,Japan,Australia,Japan,South Korea,Japan,China,Japan,France,Japan,Spain,Japan,Italia,Japan
• Study type: Interventional

Intervention(s)

Module 1 AZD9592 Monotherapy Drug: AZD9592 Varying doses of AZD9592

Module 2 AZD9592 Combination with Osimertinib Drug: AZD9592 Varying doses of AZD9592 Drug: Osimertinib tablets administered orally

Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin
Module 3 has two parts:
Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)

Outcome(s)

Primary Outcome

1. Incidence of Adverse Events (AEs) [ Time Frame: From time of Informed Consent to 30 days post last dose of AZD9592 ]
Number of patients with adverse events by system organ class and preferred term

2. Incidence of Serious Adverse Events (SAEs) [ Time Frame: From time of Informed Consent to 30 days post last dose of AZD9592 ]
Number of patients with serious adverse events by system organ class and preferred term

3. Incidence of dose-limiting toxicities (DLT) as defined in the protocol
[ Time Frame: From time of first dose of AZD9592 to end of DLT period (approximately 21 days) ]

Number of patients with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol

4. Incidence of baseline laboratory finding, ECG and vital signs changes [ Time Frame: From time of Informed Consent to 30 days post last dose of AZD9592 ]
measured by laboratory and vital sign variables over time including change from baseline

5. Proportion of patients with radiological response (ORR) [ Time Frame: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years) ]
Assessed by overall response rate (ORR) defined as the proportion of patients who have a confirmed complete or partial radiological response by the Investigator according to RECIST v1.1 (for patients in the dose expansion cohorts, only)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Age 18 years or more

- Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1

- Life expectancy 12 weeks or more

- Measurable disease per RECIST v1.1

- Adequate organ and marrow function as defined in the protocol

Additional Inclusion Criteria for Module 1:
- Histologically or cytologically confirmed metastatic or locally advanced EGFRmut., NSCLC; metastatic EGFRwt. NSCLC; recurrent or metastatic HNSCC of the oral cavity; metastatic CRC.

Additional Inclusion Criteria for Module 2:
- Histologically or cytologically confirmed metastatic NSCLC EGFRmut.

Additional Inclusion Criteria for Module 3:
- Histologically or cytologically confirmed metastatic CRC.

Exclude criteria

- History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

- Spinal cord compression or a history of leptomeningeal carcinomatosis.

- Active infection including tuberculosis and HBV, HCV or HIV

- Brain metastases unless treated (prior treatment required only for Module 1), asymptomatic, stable, and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment.

- Participants with cardiac comorbidities as defined in the study protocol

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT05647122