First in Human Study to Evaluate AZD8205 in Patients With Advanced or Metastatic Solid Malignancies

Study Overview
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Brief Summary
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This research study is studying a new compound, AZD8205, as a possible treatment for advanced or metastatic solid tumours

Official Title
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A Phase I/IIa Multi-center, Open-label Master Protocol to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Antitumor Activity of AZD8205 in Participants With Advanced or Metastatic Solid Malignancies

Conditions
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Breast Cancer, Biliary Tract Carcinoma, Ovarian Cancer, Endometrial Cancer

Intervention / Treatment
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* Drug: AZD8205


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥ 18 years Relapsed/metastatic solid tumors treated with prior adequate standard of care therapy for tumor type and stage of disease or where in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy. Measurable disease per RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1 Life expectancy ≥ 12 weeks Adequate organ and marrow function as defined in the protocol For Sub-Study 1 Part A: • Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer For Sub-Study 1 Part B: Histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort: Cohort B1 (Biliary Tract Cancer) Cohort B2 (Ovarian Cancer) Cohort B3 (Breast Cancer) Cohort B4 (Endometrial Cancer) Exclusion Criteria: Treatment with any of the following: Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 28 days (whichever is shorter) prior to the first dose of study treatment Any other anticancer treatment within the following time periods prior to the first dose of study intervention: Cytotoxic treatment: 21 days Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter) Biological products including immuno-oncology agents: 28 days Spinal cord compression or a history of leptomeningeal carcinomatosis. Brain metastases unless treated, 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. Active infection including tuberculosis and HBV, HCV or HIV 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. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses Participants with any of the following cardiac criteria: History of arrhythmia which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3); symptomatic or uncontrolled atrial fibrillation, or asymptomatic sustained ventricular tachycardia. Uncontrolled hypertension. Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months. History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening. Symptomatic heart failure (NYHA class ≥ 2). Prior or current cardiomyopathy. Severe valvular heart disease. Mean resting QTcF > 470 msec. Risk factors for QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a first time in human (FTiH) Phase I/IIa, open-label, multi-center study of AZD8205 administered to participants with advanced or metastatic solid malignancies. The study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of AZD8205.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sub-Study 1 AZD8205 Monotherapy<br>Sub-Study 1 has two parts: Part A : The aim is to determine the safety, tolerability, Recommended Phase 2 Dose(RP2D), and/or the Maximum Tolerated Dose (MTD) of AZD8205. Part B: The aim of dose expansion is to evaluate anti-tumor activity of AZD8205 as monotherapy in select solid tumors. | Drug: AZD8205<br>* AZD8205 is an antibody drug conjugate that has the potential to treat a wide variety of solid tumors including but not limited to breast cancer, Biliary Tract Cancer, ovarian, and endometrial cancers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with adverse events | Number of patients with adverse events by system organ class and preferred term | From time of Informed consent to 30 days post last dose (approximately 1 year). | 
| The number of patients with serious adverse events | 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 (approximately 1 year) | 
| The number of patients with dose-limiting toxicity (DLT), as defined in the protocol. | A DLT is defined as any toxicity that occurs from the first dose of study treatment up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation and which includes pre-defined haematological and non-haematological toxicities. | From first dose of study treatment until the end of Cycle 1 (approximately 21 days). | 
| The number of patients with changes from baseline laboratory findings, ECGs and vital signs | Description of laboratory findings and vital signs variables over time including change from baseline. | From time of informed consent to 30 days post last dose (approximately 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1). | From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years ) | 
| Duration of response (DoR) | The time from the date of first response until date of disease progression or death in the absence of disease progression. | From the first documented response to confirmed progressive disease or death ( approx. 2 years ) | 
| Progression free Survival (PFS) | The time from first dose until RECIST 1.1 defined disease progression or cessation of study treatment. | From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years ) | 
| Disease Control Rate at 12 weeks (DCR-12) | Percentage of patients with confirmed CR or PR or having SD maintained for >= 11 weeks from first dose. | Measured from first dose until progression. For each patient, this is expected to be at 12 weeks | 
| Overall Survival (OS) | The time from the date of the first dose of study treatment until death due to any cause. | From first dose of AZD8205 to death ( approx. 2 years ) | 
| Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC) | Area under the plasma concentration-time curve | From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ) | 
| Pharmacokinetics of AZD8205: Maximum plasma concentration of the study drug (Cmax) | Maximum observed plasma concentration of the study drug | From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ) | 
| Pharmacokinetics of AZD8205: Time to maximum plasma concentration of the study drug (T-max) | Time to maximum observed plasma concentration of the study drug | From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ) | 
| Pharmacokinetics of AZD8205: Clearance | A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time. | From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ) | 
| Pharmacokinetics of AZD8205: Terminal elimination half-life (t 1/2) | Terminal elimination half life. | From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ) | 
| Immunogenicity of AZD8205. | The number and percentage of participants who develop ADAs. | From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First In Human, antibody drug conjugate, cancer, solid tumour, Phase I