First in Human Study of AZD9592 in Solid Tumors (EGRET)

AstraZeneca

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumours; Colorectal Neoplasms; Head and Neck Neoplasms; Carcinoma Non-small Cell Lung

Treatments: Drug: Bevacizumab; Drug: Leucovorin; Drug: 5-Fluorouracil (5-FU); Drug: AZD9592; Drug: Osimertinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05647122

D9350C00001

2022-501570-18-00 (Registry Identifier)

Details and patient eligibility

About

This is a first-in-human (FIH) Phase I, multi-center, open-label, study of AZD9592, in patients with advanced solid tumors. The study consists of several study modules, each evaluating the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), pharmacodynamics, anti-tumor activity, and immunogenicity of AZD9592, as monotherapy or in combination with anti-cancer agents.

Enrollment: 403 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
• Life expectancy ≥ 12 weeks
• 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.

Key Exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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403 participants in 3 patient groups

Module 1 AZD9592 Monotherapy

Experimental group

Description:

Module 1 has two parts: Part A aims to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AZD9592. Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 as monotherapy in select solid tumors

Treatment:

Drug: AZD9592

Module 2 AZD9592 Combination with Osimertinib

Experimental group

Description:

Module 2 has two parts: Part A aims to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with Osimertinib. Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with Osimertinib in NSCLC EGFRm

Treatment:

Drug: Osimertinib

Drug: AZD9592

Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin

Experimental group

Description:

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)

Treatment:

Drug: AZD9592

Drug: 5-Fluorouracil (5-FU)

Drug: Leucovorin

Drug: Bevacizumab