First in Human Study of AZD9592 in Solid Tumors

NCT05647122 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: D9350C000012022-501570-18-00
• Study Type: interventional
• Target: 403
• Locations: 11 countries
• Sites: 50

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Incidence of Adverse Events (AEs)

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

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

• Incidence of Serious Adverse Events (SAEs)

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

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

• 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

  From time of first dose of AZD9592 to end of DLT period (approximately 21 days)

• Incidence of baseline laboratory finding, ECG and vital signs changes

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

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

• 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)

  From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)

Secondary Outcomes (12)

• 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)

• 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)

• 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)

• 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)

• Overall Survival (OS)

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

Study Arms (3)

Module 1 AZD9592 Monotherapy

EXPERIMENTAL

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

Module 2 AZD9592 Combination with Osimertinib

EXPERIMENTAL

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; Drug: Osimertinib

Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin

EXPERIMENTAL

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)

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

Interventions

Leucovorin DRUG

IV infusion

Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin

Bevacizumab DRUG

IV infusion

Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin

AZD9592 DRUG

Varying doses of AZD9592

Module 1 AZD9592 Monotherapy; Module 2 AZD9592 Combination with Osimertinib; Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin

Osimertinib DRUG

tablets administered orally

Module 2 AZD9592 Combination with Osimertinib

5-Fluorouracil (5-FU) DRUG

IV infusion

Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Histologically or cytologically confirmed metastatic or locally advanced EGFRmut., NSCLC; metastatic EGFRwt. NSCLC; recurrent or metastatic HNSCC of the oral cavity; metastatic CRC.
• Histologically or cytologically confirmed metastatic NSCLC EGFRmut.
• Histologically or cytologically confirmed metastatic CRC.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (50)

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

Irvine, California, 92618, United States

WITHDRAWN

Research Site

North Haven, Connecticut, 06473, United States

RECRUITING

Research Site

Washington D.C., District of Columbia, 20016, United States

RECRUITING

Research Site

Chicago, Illinois, 60637, United States

RECRUITING

Research Site

Baltimore, Maryland, 21224, United States

RECRUITING

Research Site

Baltimore, Maryland, 21231, United States

RECRUITING

Research Site

Milford, Massachusetts, 01757, United States

RECRUITING

Research Site

Mineola, New York, 11501, United States

RECRUITING

Research Site

New York, New York, 10016, United States

RECRUITING

Research Site

New York, New York, 10021, United States

RECRUITING

Research Site

New York, New York, 10029, United States

RECRUITING

Research Site

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Research Site

Providence, Rhode Island, 02903, United States

RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

Fairfax, Virginia, 22031, United States

RECRUITING

Research Site

Kogarah, 2217, Australia

RECRUITING

Research Site

Melbourne, 3000, Australia

RECRUITING

Research Site

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

Research Site

Toronto, Ontario, M5G 1X6, Canada

RECRUITING

Research Site

Beijing, 100142, China

RECRUITING

Research Site

Beijing, 100142, China

NOT YET RECRUITING

Research Site

Chongqing, 400030, China

RECRUITING

Research Site

Guangzhou, 510100, China

RECRUITING

Research Site

Harbin, 150049, China

NOT YET RECRUITING

Research Site

Wuhan, 430022, China

RECRUITING

Research Site

Marseille, 13385, France

RECRUITING

Research Site

Rennes, 35000, France

RECRUITING

Research Site

Villejuif, 94805, France

RECRUITING

Research Site

Milan, 20162, Italy

RECRUITING

Research Site

Orbassano, 10043, Italy

RECRUITING

Research Site

Rozzano, 20089, Italy

RECRUITING

Research Site

Verona, 37134, Italy

RECRUITING

Research Site

Chūōku, 104-0045, Japan

RECRUITING

Research Site

Kashiwa, 277-8577, Japan

RECRUITING

Research Site

Kōtoku, 135-8550, Japan

RECRUITING

Research Site

Osaka, 541-8567, Japan

RECRUITING

Research Site

Kuala Lumpur, 59100, Malaysia

RECRUITING

Research Site

Kuching, 93586, Malaysia

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 03722, South Korea

RECRUITING

Research Site

Seoul, 05505, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Barcelona, 8035, Spain

RECRUITING

Research Site

Madrid, 28040, Spain

RECRUITING

Research Site

Seville, 41013, Spain

RECRUITING

Research Site

Taichung, 40705, Taiwan

RECRUITING

Research Site

Taipei, 10002, Taiwan

RECRUITING

Research Site

Taipei, 11217, Taiwan

RECRUITING

Research Site

Taoyuan District, 333, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms; Colorectal Neoplasms; Neoplasms

Interventions

osimertinib; Fluorouracil; Leucovorin; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Charu Aggarwal, MD, MPH

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: December 12, 2022
• Study Start: December 21, 2022
• Primary Completion (Estimated): October 6, 2027
• Study Completion (Estimated): October 6, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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

Locations

TW (4); US (16); JP (4); CA (2); KR (4); ES (3); FR (3); AU (2); CN (6); MY (2); IT (4)