Advanced Solid Tumours, Carcinoma Non-small Cell Lung, Colorectal Neoplasms, Head and Neck Neoplasms
Conditions
Keywords
Cancer, First in Human, Antibody Drug Conjugate, Solid Tumour, Phase I
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.
Interventions
DRUGAZD9592
Varying doses of AZD9592
DRUGOsimertinib
tablets administered orally
DRUG5-Fluorouracil (5-FU)
IV infusion
DRUGLeucovorin
IV infusion
DRUGBevacizumab
IV infusion
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 2 weeks prior to start of study treatment. * Participants with cardiac comorbidities as defined in the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Incidence of dose-limiting toxicities (DLT) as defined in the protocol | 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 | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 |
| 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 |
| 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. |
| 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 |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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 |
Countries
Australia, Canada, China, France, Italy, Japan, Malaysia, South Korea, Spain, Taiwan, United States
Contacts
PRINCIPAL_INVESTIGATORCharu Aggarwal, MD, MPH
University of Pennsylvania
Outcome results
None listed