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

JRCT ID: jRCT2031210585

Registered date:28/01/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Breast Cancer, Biliary Tract Carcinoma, Ovarian Cancer, Endometrial Cancer
• Date of first enrollment: 24/01/2022
• Target sample size: 198
• Countries of recruitment: US,Japan,Australia,Japan,Canada,Japan,China,Japan,South Korea,Japan,Taiwan,Japan,Thailand,Japan,United of Kingdom,Japan
• Study type: Interventional

Intervention(s)

Drug: AZD8205
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, cholangiocarcinoma, ovarian, and endometrial cancers

Outcome(s)

Primary Outcome

- The number of patients with adverse events [ Time Frame: From time of Informed consent to 30 days post last dose (approximately 1 year). ]
Number of patients with adverse events by system organ class and preferred term

- The number of patients with serious adverse events [ Time Frame: From time of Informed consent to 30 days post last dose (approximately 1 year) ]
Number of patients with serious adverse events by system organ class and preferred term

- The number of patients with dose-limiting toxicity (DLT), as defined in the protocol. [ Time Frame: From first dose of study treatment until the end of Cycle 1 (approximately 21 days). ]
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.

- The number of patients with changes from baseline laboratory findings, ECGs and vital signs [ Time Frame: From time of informed consent to 30 days post last dose (approximately 1 year) ]
Description of laboratory findings and vital signs variables over time including change from baseline.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Age18 years or more

- 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 expectancy12 weeks or more

- 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, CCA or endometrial cancer

For Sub-Study 1 Part B:

- Histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort:
1.Cohort B1 (Biliary Tract Cancer)
2.Cohort B2 (Ovarian Cancer)
3.Cohort B3 (Breast Cancer)
4.Cohort B4 (Endometrial Cancer)

Exclude criteria

- Treatment with any of the following:

1. Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment

2. 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

3. Any other anticancer treatment within the following time periods prior to the first dose of study intervention:

a. Cytotoxic treatment: 21 days

b. Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter)

c. 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:

1. 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.

2. Uncontrolled hypertension.

3. Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months.

4. History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening.

5. Symptomatic heart failure (NYHA class 2 or more).

6. Prior or current cardiomyopathy.

7. Severe valvular heart disease.

8. Mean resting QTcF > 470 msec.

9. 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.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT05123482