Clinical trial NCT05647122: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumours
Carcinoma Non-small Cell Lung
Head and Neck Neoplasms
Colorectal Neoplasms
Keywords: Cancer
First in Human
Antibody Drug Conjugate
Solid Tumour
Phase I
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-12-12
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: From time of Informed Consent to 30 days post last dose of AZD9592
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: From time of Informed Consent to 30 days post last dose of AZD9592
measure: Incidence of dose-limiting toxicities (DLT) as defined in the protocol
timeFrame: From time of first dose of AZD9592 to end of DLT period (approximately 21 days)
measure: Incidence of baseline laboratory finding, ECG and vital signs changes
timeFrame: From time of Informed Consent to 30 days post last dose of AZD9592
measure: Proportion of patients with radiological response (ORR)
timeFrame: 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:
measure: Objective Response Rate (ORR)
timeFrame: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
measure: Duration of Response (DoR)
timeFrame: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
measure: Disease Control Rate (DCR) at 12 weeks
timeFrame: 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)
measure: Progression free Survival (PFS)
timeFrame: From date of first dose of AZD9592 up until date of progression or death due to any cause (approximately 2 years)
measure: Overall Survival (OS)
timeFrame: From date of first dose of AZD9592 up until the date of death due to any cause (approximately 2 years)
measure: Pharmacokinetics of AZD9592: Plasma PK concentrations
timeFrame: From date of first dose of AZD9592 up until 30 days post last dose
measure: Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC)
timeFrame: From date of first dose of AZD9592 up until 30 days post last dose
measure: Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max)
timeFrame: From date of first dose of AZD9592 up until 30 days post last dose
measure: Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max)
timeFrame: From date of first dose of AZD9592 up until 30 days post last dose
measure: Pharmacokinetics of AZD9592: Clearance
timeFrame: From date of first dose of AZD9592 up until 30 days post last dose
measure: Pharmacokinetics of AZD9592: Half-life
timeFrame: From date of first dose of AZD9592 up until 30 days post last dose
measure: Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA)
timeFrame: From date of first dose of AZD9592 up until 30 days post last dose
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Irvine
country: United States
facility: Research Site
state: California
city: North Haven
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Milford
country: United States
facility: Research Site
state: Massachusetts
city: Mineola
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Houston
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Kogarah
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Harbin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Verona
country: Italy
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
Study officials:
affiliation: University of Pennsylvania
name: Charu Aggarwal, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: