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

Primary Purpose

Advanced Solid Tumours, Carcinoma Non-small Cell Lung, Head and Neck Neoplasms

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AZD9592

Osimertinib

About this trial

This is an interventional treatment trial for Advanced Solid Tumours focused on measuring Cancer, First in Human, Antibody Drug Conjugate, Solid Tumour, Phase I

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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; recurrant or metastatic HNSCC of the oral cavity Additional Inclusion Criteria for Module 2: • Histologically or cytologically confirmed metastatic NSCLC EGFRmut. 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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Module 1 AZD9592 Monotherapy

Module 2 AZD9592 Combination with Osimertinib

Arm 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

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

Outcomes

Primary Outcome Measures

Incidence of Adverse Events (AEs)

Number of patients with adverse events by system organ class and preferred term

Incidence of Serious Adverse Events (SAEs)

Number of patients with serious adverse events by system organ class and preferred term

Incidence of dose-limiting toxicities (DLT) as defined in the protocol

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

Incidence of baseline laboratory finding, ECG and vital signs changes

measured by laboratory and vital sign variables over time including change from baseline

Proportion of patients with radiological response (ORR)

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)

Secondary Outcome Measures

Objective Response Rate (ORR)

The percentage or number of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST v1.1)

Duration of Response (DoR)

The time from date of first response until date of disease progression or last evaluable assessment (RECIST v1.1) in the absence of progression

Disease Control Rate (DCR) at 12 weeks

The percentage of patients with confirmed CR or PR or having SD maintained (RECIST v1.1) for >=11 weeks from first dose

Progression free Survival (PFS)

The time from first dose until RECIST 1.1 defined disease progression or death due to any cause

Overall Survival (OS)

The time from the date of the first dose of study treatment until death due to any cause.

Pharmacokinetics of AZD9592: Plasma PK concentrations

Measurement of plasma concentrations of AZD9592, total antibody and total unconjugated warhead

Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC)

Measurement of PK parameters: Area under the concentration time curve (AUC)

Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max)

Measurement of PK parameters: Maximum observed plasma concentration of the study drug (C-max)

Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max)

Measurement of PK parameters: Time to maximum observed plasma concentration of the study drug (T-max)

Pharmacokinetics of AZD9592: Clearance

Measurement of PK parameters: the volume of plasma from which the study drug is completely removed per unit time (Clearance)

Pharmacokinetics of AZD9592: Half-life

Measurement of PK parameters: Terminal elimination half-life (t 1/2)

Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA)

Evaluating the number and percentage of patients who develop Anti-drug antibody (ADA) during treatment

Full Information

NCT ID

NCT05647122

First Posted

November 18, 2022

Last Updated

September 15, 2023

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT05647122

Brief Title

First in Human Study of AZD9592 in Solid Tumors

Acronym

EGRET

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 22, 2022 (Actual)

Primary Completion Date

January 16, 2025 (Anticipated)

Study Completion Date

January 16, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Solid Tumours, Carcinoma Non-small Cell Lung, Head and Neck Neoplasms

Keywords

Cancer, First in Human, Antibody Drug Conjugate, Solid Tumour, Phase I

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

108 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Module 1 AZD9592 Monotherapy

Arm Type

Experimental

Arm Description

Arm Title

Module 2 AZD9592 Combination with Osimertinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

AZD9592

Intervention Description

Varying doses of AZD9592

Intervention Type

Drug

Intervention Name(s)

Osimertinib

Intervention Description

tablets administered orally

Primary Outcome Measure Information:

Title

Incidence of Adverse Events (AEs)

Description

Number of patients with adverse events by system organ class and preferred term

Time Frame

From time of Informed Consent to 30 days post last dose of AZD9592

Title

Incidence of Serious Adverse Events (SAEs)

Description

Number of patients with serious adverse events by system organ class and preferred term

Time Frame

From time of Informed Consent to 30 days post last dose of AZD9592

Title

Incidence of dose-limiting toxicities (DLT) as defined in the protocol

Description

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

Time Frame

From time of first dose of AZD9592 to Day 21 (Cycle 1)

Title

Incidence of baseline laboratory finding, ECG and vital signs changes

Description

measured by laboratory and vital sign variables over time including change from baseline

Time Frame

From time of Informed Consent to 30 days post last dose of AZD9592

Title

Proportion of patients with radiological response (ORR)

Description

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)

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

The percentage or number of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST v1.1)

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)

Title

Duration of Response (DoR)

Description

The time from date of first response until date of disease progression or last evaluable assessment (RECIST v1.1) in the absence of progression

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)

Title

Disease Control Rate (DCR) at 12 weeks

Description

The percentage of patients with confirmed CR or PR or having SD maintained (RECIST v1.1) for >=11 weeks from first dose

Time Frame

From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (for each patient this is expected to be measured at 12 weeks)

Title

Progression free Survival (PFS)

Description

The time from first dose until RECIST 1.1 defined disease progression or death due to any cause

Time Frame

From date of first dose of AZD9592 up until date of progression or death due to any cause (approximately 2 years)

Title

Overall Survival (OS)

Description

The time from the date of the first dose of study treatment until death due to any cause.

Time Frame

From date of first dose of AZD9592 up until the date of death due to any cause (approximately 2 years)

Title

Pharmacokinetics of AZD9592: Plasma PK concentrations

Description

Measurement of plasma concentrations of AZD9592, total antibody and total unconjugated warhead

Time Frame