Back to Trials
NCT05123482PHASE1, PHASE2Recruiting

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

AstraZeneca

Start Date

10/18/2021

Completion Date

9/29/2027

Summary

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

Detailed Description

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

Eligibility Criteria

Age Range: 18 years to No maximum

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 bone marrow, hepatic, and renal function as defined in the protocol Additional Inclusion Criteria For Sub-Study 1 Part A: • Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer Additional Inclusion Criteria 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) 5. Cohort B5 (Squamous Non-Small Cell Lung Cancer) Additional Inclusion Criteria For Sub-Study 2 Part A: * Minimum body weight ≥ 30 kg. * Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC, endometrial cancer or squamous non-small cell lung cancer. Additional Inclusion Criteria For Sub-Study 3 Part A: * Minimum body weight ≥ 30 kg (for participants enrolled in cohorts including rilvegostomig only). * Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC, endometrial cancer or squamous non-small cell lung cancer. Additional Inclusion Criteria For Sub-Study 4 Part A: * Minimum body weight ≥ 30 kg (for participants enrolled in cohorts including rilvegostomig only). * Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, endometrial cancer or squamous non-small cell lung cancer. * Participants must have progressed following at least one but no more than 3 prior lines of treatment for metastatic or relapsed disease and have no satisfactory alternative treatment option as judged by the Investigator. Key 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. * Patients with history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML (as determined by prior diagnostic investigation) Additional Exclusion Criteria For Sub-Study 2 Part A: * Thromboembolic event within 3 months before the first dose of study intervention - No longer applicable per amendment 7 * 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. * History of organ transplant Additional Exclusion Criteria For Sub-Study 2 Part B • Previous treatment with any therapy that contains a TOP1i (eg. irinotecan, topotecan, trastuzumab deruxtecan, etc.) Additional Exclusion Criteria For Sub-Study 3 Part A: * Concomitant use of medications or herbal supplements known to be strong cytochrome P (CYP) 3A4 inducers/inhibitors. * Any history of persisting (\> 2 weeks) severe cytopenia due to any cause * Patients with any known predisposition to bleeding * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib. * Previous treatment with any therapy that contains a TOP1i (eg. irinotecan, topotecan, trastuzumab deruxtecan, etc.) Additional Exclusion Criteria For Sub-Study 4 Part A: * Patients have received prior therapy with AZD9574 or more than 1 prior line of any other PARPi-based regimen * Concomitant use of medications or herbal supplements known to be strong cytochrome P (CYP) 3A4 inducers/inhibitors. * Previous treatment with rilvegostomig for the cohort treated with rilvegostomig * Previous treatment with any therapy that contains a TOP1i (eg. irinotecan, topotecan, trastuzumab deruxtecan, etc.) * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9574

Interventions

DRUG

AZD8205

DRUG

AZD8205 and AZD2936 (Rilvegostomig)

DRUG

AZD8205 and AZD5305 (saruparib)

DRUG

AZD8205 and AZD5305 (saruparib) and AZD2936 (rilvegostomig)

DRUG

AZD8205 in combination with AZD9574

DRUG

AZD8205 in combination with AZD9574 plus rilvegostomig (AZD2936)

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Breast CancerBiliary Tract CarcinomaOvarian CancerEndometrial CancerSquamous Non-Small Cell Lung Cancer

Locations

Research Site

Duarte, California 91010

United States

Research Site

Irvine, California 92618

United States

Research Site

Santa Monica, California 90404

United States

Research Site

Santa Rosa, California 95403

United States

Research Site

Shreveport, Louisiana 71103

United States

Research Site

Baltimore, Maryland 21231

United States

Research Site

Boston, Massachusetts 02215

United States

Research Site

St Louis, Missouri 63110

United States

Research Site

Albuquerque, New Mexico 87109

United States

Research Site

Commack, New York 11725

United States

Research Site

New York, New York 10029

United States

Research Site

Charlotte, North Carolina 28204

United States

Research Site

Pittsburgh, Pennsylvania 15213

United States

Research Site

Houston, Texas 77030

United States

Research Site

Clayton, 3168

Australia

Research Site

Melbourne, VIC 3000

Australia

Research Site

Nedlands, 6009

Australia

Research Site

Anderlecht, 1070

Belgium

Research Site

Leuven, 3000

Belgium

Research Site

Calgary, Alberta T2N 5G2

Canada

Research Site

Vancouver, British Columbia V5Z 4E6

Canada

Research Site

Ottawa, Ontario K1H 8L6

Canada

Research Site

Toronto, Ontario M5G 2M9

Canada

Research Site

Montreal, Quebec H4A 3J1

Canada

Research Site

Beijing, 100142

China

Research Site

Beijing, 100142

China

Research Site

Changsha, 410013

China

Research Site

Changsha, 410013

China

Research Site

Chongqing, 400030

China

Research Site

Guangzhou, 510060

China

Research Site

Kunming, 650118

China

Research Site

Shandong,

China

Research Site

Budapest, 1062

Hungary

Research Site

Budapest, 1082

Hungary

Research Site

Budapest, 1122

Hungary

Research Site

Milan, 20141

Italy

Research Site

Milan, 20159

Italy

Research Site

Modena, 41125

Italy

Research Site

Roma, 00168

Italy

Research Site

Chūōku, 104-0045

Japan

Research Site

Hidaka-shi, 350-1298

Japan

Research Site

Kashiwa, 277-8577

Japan

Research Site

Kōtoku, 135-8550

Japan

Research Site

Kurume-shi, 830-0011

Japan

Research Site

Sunto-gun, 411-8777

Japan

Research Site

Amsterdam, 1066 CX

Netherlands

Research Site

Gdansk, 80-214

Poland

Research Site

Warsaw, 02-781

Poland

Research Site

Seoul, 03080

South Korea

Research Site

Seoul, 03722

South Korea

Research Site

Seoul, 05505

South Korea

Research Site

Seoul, 06351

South Korea

Research Site

Barcelona, 8035

Spain

Research Site

L'Hospitalet de Llobregat, 08908

Spain

Research Site

Madrid, 28027

Spain

Research Site

Málaga, 29010

Spain

Research Site

Pamplona, 31008

Spain

Research Site

Taichung, 40705

Taiwan

Research Site

Tainan, 704

Taiwan

Research Site

Taipei, 10002

Taiwan

Research Site

Taipei, 11259

Taiwan

Research Site

Taoyuan, 333

Taiwan

Research Site

Bangkok, 10330

Thailand

Research Site

Chiang Mai, 50200

Thailand

Research Site

Cambridge, CB2 0XY

United Kingdom

Research Site

Cardiff, CF14 2TL

United Kingdom

Research Site

London, EC1A 7BE

United Kingdom