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A Phase I/IIa Study of AZD8205 Given Alone or in Combination With Anticancer Drugs, in Participants With Advanced or Metastatic Solid Malignancies

PHASE1PHASE2RECRUITING

This research study is studying a new compound, AZD8205, as a possible treatment for advanced or metastatic solid tumours alone or in combination with anti-cancer agents.

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Study details:

This study is a Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination with Anticancer Agents in Participants with Advanced Solid Tumors.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer

Minimum body weight ≥ 30 kg.

Exclusion 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:

1. Cytotoxic treatment: 21 days

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

3. 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).

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.

Thromboembolic event within 3 months before the first dose of study intervention.

Experienced a toxicity that led to permanent discontinuation of prior immunotherapy.

Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2021-10-18

Primary completion: 2025-12-30

Study completion finish: 2025-12-30

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT05123482

Intervention or treatment

DRUG: AZD8205

DRUG: AZD8205 and AZD2936 (Rilvegostomig)

Conditions

• Breast Cancer
• Ovarian Cancer
• Endometrial Cancer
• Biliary Tract Carcinoma

Condition: Breast Cancer, Ovarian Cancer and more
DRUG: AZD8205 and other drugs
Clayton, Not Specified, Australia and more
Sponsor: AstraZeneca

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Research Site

Research sites nearby

Select from list below to view details:

Research Site
Clayton, Not Specified, Australia
Research Site
South Brisbane, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Sub-Study 1 AZD8205 Monotherapy 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 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
EXPERIMENTAL: Sub Study 2: AZD8205 in combination with rilvegostomig Sub-Study 2 has two parts: Part A : Dose escalation to determine the safety, tolerability of AZD8205 + rilvegostomig Part B: Dose expansion to evaluate anti-tumor activity of AZD8205 + rilvegostomig in select solid tumors.	DRUG: AZD8205 and AZD2936 (Rilvegostomig) 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. Rilvegostomig is a bispecific antibody that specifically binds to human TIGIT and PD-1 and is a potential anticancer therapy in patients with advanced or metastatic solid tumors.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Sub-Study 1 AZD8205 Monotherapy

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

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

EXPERIMENTAL: Sub Study 2: AZD8205 in combination with rilvegostomig

Sub-Study 2 has two parts:
Part A : Dose escalation to determine the safety, tolerability of AZD8205 + rilvegostomig Part B: Dose expansion to evaluate anti-tumor activity of AZD8205 + rilvegostomig in select solid tumors.

DRUG: AZD8205 and AZD2936 (Rilvegostomig)

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.
Rilvegostomig is a bispecific antibody that specifically binds to human TIGIT and PD-1 and is a potential anticancer therapy in patients with advanced or metastatic solid tumors.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome 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

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome 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 (RECIST 1.1) 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 (RECIST 1.1).	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 )
Sub Study 1: AZD8205 monotherapy Pharmacodynamics	To assess the intratumoral pharmacodynamic biomarkers (gamma H2AX H-scores) to AZD8205 when administered as a monotherapy.	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Sub Study 2: AZD8205 in combination with AZD2936 Pharmacodynamics	To assess the change in intratumoral pharmacodynamic biomarkers (gamma H2AX H-scores) to AZD8205 when administered in combination with rilvegostomig.	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )

Frequently Asked Questions

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References

Clinical Trials Gov: A Phase I/IIa Study of AZD8205 Given Alone or in Combination With Anticancer Drugs, in Participants With Advanced or Metastatic Solid Malignancies