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

Purpose

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

Conditions

  • Breast Cancer
  • Biliary Tract Carcinoma
  • Ovarian Cancer
  • Endometrial Cancer
  • Squamous Non-Small Cell Lung Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
The study consists a master protocol with sub studies each evaluating the safety and tolerability of AZD8205 dosed as monotherapy, or in Combination with Anticancer Agents in Participants with Advanced Solid Tumours: Sub Study 1 (AZD8205 monotherapy) - Part A Dose Escalation - Part B Dose Expansion Sub Study 2 (AZD8205 in combination with rilvegostomig) - Part A Dose Escalation - Part B Dose Expansion Sub Study 3 (AZD8205 in combination with saruparib with or without rilvegostomig) - Part A Dose Escalation - Part B Dose Expansion Sub Study 4 (AZD8205 in combination with AZD9574 with or without rilvegostomig) - Part A Dose Escalation - Part B Dose Expansion
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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, endometrial cancers and squamous non-small cell lung 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, endometrial cancers and squamous non-small cell lung 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.
Experimental
Sub-Study 3 AZD8205 in combination with saruparib, with or without rilvegostomig 		Sub-Study 3 has two parts: Part A : Dose escalation to determine the safety, tolerability of AZD8205 + saruparib. Rilvegostomig may be added in a triplet combination once an AZD8205 + saruparib combination dose/schedule has been considered safe. Part B: Dose expansion to evaluate anti-tumor activity of AZD8205 + saruparib with or without rilvegostomig in select solid tumors.
  • Drug: AZD8205 and AZD5305 (saruparib)
    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, endometrial and squamous non-small cell lung cancers. Saruparib is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors.
  • Drug: AZD8205 and AZD5305 (saruparib) 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, endometrial and squamous non-small cell lung cancers. Saruparib is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors. 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.
Experimental
Sub-Study 4: AZD8205 in combination with AZD9574 with or without rilvegostomig (AZD2936) 		Sub-Study 4 has two parts: Part A : Dose escalation to determine the safety, tolerability of AZD8205 + AZD9574. Rilvegostomig may be added in a triplet combination once an AZD8205 + AZD9574 combination dose/schedule has been considered safe. Part B: may be added in the future depending on emerging data, following a formal protocol amendment.
  • Drug: AZD8205 in combination with AZD9574
    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, endometrial and squamous non-small cell lung cancers. AZD9574 is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors.
  • Drug: AZD8205 in combination with AZD9574 plus rilvegostomig (AZD2936)
    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, endometrial and squamous non-small cell lung cancers. AZD9574 is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors. 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.

Recruiting Locations

Research Site
Santa Monica, California 90404

Research Site
Santa Rosa, California 95403

Research Site
Baltimore, Maryland 21231

Research Site
Boston, Massachusetts 02215

Research Site
St Louis, Missouri 63110

Research Site
Albuquerque, New Mexico 87109

Research Site
Commack, New York 11725

Research Site
Charlotte, North Carolina 28204

Research Site
Pittsburgh, Pennsylvania 15213

Research Site
Houston, Texas 77030

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

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