EGRET: First in Human Study of AZD9592 in Solid Tumors

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05647122
• Collaborator: (none)
• Enrollment: 108
• Locations: 14
• Arms: 2
• Anticipated Duration (Months): 21.5
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumours; Carcinoma Non-small Cell Lung; Head and Neck Neoplasms	Drug: AZD9592; Drug: Osimertinib	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 108 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 21, 2022
• Anticipated Primary Completion Date: Oct 4, 2024
• Anticipated Study Completion Date: Oct 4, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Module 1 AZD9592 Monotherapy 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	Drug: AZD9592; Varying doses of AZD9592
Experimental: Module 2 AZD9592 Combination with Osimertinib 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	Drug: AZD9592; Varying doses of AZD9592; Drug: Osimertinib; tablets administered orally

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events (AEs) [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) [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 [From time of first dose of AZD9592 to Day 21 (Cycle 1)]

   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 [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) [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)

Secondary Outcome Measures

1. Objective Response Rate (ORR) [From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)]

   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)

2. Duration of Response (DoR) [From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)]

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

3. Disease Control Rate (DCR) at 12 weeks [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)]

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

4. Progression free Survival (PFS) [From date of first dose of AZD9592 up until date of progression or death due to any cause (approximately 2 years)]

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

5. Overall Survival (OS) [From date of first dose of AZD9592 up until the date of death due to any cause (approximately 2 years)]

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

6. Pharmacokinetics of AZD9592: Plasma PK concentrations [From date of first dose of AZD9592 up until 30 days post last dose]

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

7. Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC) [From date of first dose of AZD9592 up until 30 days post last dose]

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

8. Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max) [From date of first dose of AZD9592 up until 30 days post last dose]

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

9. Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max) [From date of first dose of AZD9592 up until 30 days post last dose]

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

10. Pharmacokinetics of AZD9592: Clearance [From date of first dose of AZD9592 up until 30 days post last dose]

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

11. Pharmacokinetics of AZD9592: Half-life [From date of first dose of AZD9592 up until 30 days post last dose]

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

12. Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA) [From date of first dose of AZD9592 up until 30 days post last dose]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Duarte	California	United States	91010
2	Research Site	Irvine	California	United States	92618
3	Research Site	Chicago	Illinois	United States	60637
4	Research Site	Mineola	New York	United States	11501
5	Research Site	New York	New York	United States	10029
6	Research Site	Philadelphia	Pennsylvania	United States	19104
7	Research Site	Providence	Rhode Island	United States	02903
8	Research Site	Houston	Texas	United States	77030
9	Research Site	Fairfax	Virginia	United States	22031
10	Research Site	Melbourne		Australia	3000
11	Research Site	Chuo-ku		Japan	104-0045
12	Research Site	Kashiwa		Japan	277-8577
13	Research Site	Madrid		Spain	28040
14	Research Site	Sevilla		Spain	41013

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Charu Aggarwal, MD, MPH, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05647122
• Other Study ID Numbers: D9350C00001
• First Posted: Dec 12, 2022
• Last Update Posted: Jan 6, 2023
• Last Verified: Dec 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Cancer; First in Human; Antibody Drug Conjugate; Solid Tumour; Phase I
• Additional relevant MeSH terms: Head and Neck Neoplasms; Osimertinib

Study Results

No Results Posted as of Jan 6, 2023