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

• ClinicalTrials.gov Identifier: NCT05647122
• Recruitment Status: Recruiting
• First Posted: December 12, 2022
• Last Update Posted: April 26, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: November 18, 2022
• First Posted Date: December 12, 2022
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: December 22, 2022
• Estimated Primary Completion Date: October 29, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2023)

• 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
• 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
• 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
• 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
• 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)

Original Primary Outcome Measures (submitted: December 2, 2022)

• 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
• 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
• Incidence of dose-limiting toxicities (DLT) as defined in the protocol [ Time Frame: 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
• 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
• 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)

Current Secondary Outcome Measures (submitted: December 2, 2022)

• Objective Response Rate (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) ]
  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) [ 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) ]
  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 [ 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) ]
  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) [ Time Frame: 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
• Overall Survival (OS) [ Time Frame: 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.
• Pharmacokinetics of AZD9592: Plasma PK concentrations [ Time Frame: 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
• Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC) [ Time Frame: 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)
• Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max) [ Time Frame: 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)
• Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max) [ Time Frame: 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)
• Pharmacokinetics of AZD9592: Clearance [ Time Frame: 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)
• Pharmacokinetics of AZD9592: Half-life [ Time Frame: 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)
• Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA) [ Time Frame: 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First in Human Study of AZD9592 in Solid Tumors
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: AZD9592
  Varying doses of AZD9592
• Drug: Osimertinib
  tablets administered orally
• Drug: 5-Fluorouracil (5-FU)
  IV infusion
• Drug: Leucovorin
  IV infusion
• Drug: Bevacizumab
  IV infusion

Study Arms

• 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

  Intervention: Drug: 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

  Interventions:

  • Drug: AZD9592
  • Drug: Osimertinib
• Experimental: 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)

  Interventions:

  • Drug: AZD9592
  • Drug: 5-Fluorouracil (5-FU)
  • Drug: Leucovorin
  • Drug: Bevacizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 28, 2024): 162
• Original Estimated Enrollment (submitted: December 2, 2022): 108
• Estimated Study Completion Date: October 29, 2025
• Estimated Primary Completion Date: October 29, 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: AstraZeneca Clinical Study Information Center; 1-877-240-9479; information.center@astrazeneca.com

• Listed Location Countries: Spain, Australia, Canada, China, France, Italy, Japan, Korea, Republic of, Malaysia, Taiwan, United States

Administrative Information

• NCT Number: NCT05647122
• Other Study ID Numbers: D9350C00001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: AstraZeneca
• Verification Date: April 2024