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Clinical Trial 20628

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT04089553

Phase: Phase II
Principal Investigator: Zhang, Jingsong

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Overview

Study Title

A Phase II, Open-Label, Study to Assess the Efficacy, Safety, and Tolerability of AZD4635 in Combination with Durvalumab and in Combination with Cabazitaxel and Durvalumab in Patients Who Have Progressive Metastatic Castrate-Resistant Prostate Cancer (AARDVARC)

Summary

This is an open-label Phase II modular study in patients with prostate cancer which will assess safety, efficacy, and tolerability of AZD4635 in combination with other therapeutic agents in different treatment arms (referred to as modules). Combinations to be studied include: 1) Module 1: AZD4635 plus durvalumab; 2) Module 2: AZD4635 plus oleclumab; 3) Module 3: AZD4635 plus durvalumab plus oleclumab. The protocol may be amended to include other combinations.

Objective

- To determine the efficacy (as assessed by radiographic progression free survival [rPFS]) of AZD4635 plus durvalumab and separately of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC.

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy; Therapy (NOS)

Medications

AMP-514 (Durvalumab); AZD4635 (); Cabazitaxel (); Durvalumab (); Jevtana (Cabazitaxel); MEDI4736 (Durvalumab)

Inclusion Criteria

Inclusion Criteria for all Patients in all Modules:

Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses

Patient must be 18 years of age or older at the time of signing the ICF

Patients must have prostate cancer with histological or cytological confirmation

Patients must have previously received and progressed on standard-of-care therapy(ies)

Patients must be able to provide an archival tumor tissue sample. If archival tumor tissue is not available, then tissue from a fresh tumor biopsy is required.

All patients will be required to have a site of disease that is safely accessible for biopsy (paired) upon enrollment unless there are sufficient paired samples for the analysis. Accessible lesions are defined as those which are biopsiable (at screening) and amenable to repeat biopsy (after 2 weeks of AZD4635 therapy), unless clinically contraindicated. The provision of paired biopsies will be closely monitored to ensure the desired number of biopsiable patients are enrolled and investigators are aware of this requirement at all times.

Patients with measurable disease must have at least 1 documented lesion on either a bone scan or a computed tomography (CT)/ magnetic resonance imaging (MRI) scan that can be followed for response and is suitable for repeated measurement, or patients with non-measurable disease must have measurable PSA ≥1.0 ng/mL if the confirmed rise is the only indication of progression (excluding small cell carcinoma)

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no clinical deterioration over the previous 2 weeks prior to the 28-day screening period and likely able to complete at least 12 weeks of treatment.

Ability to swallow and retain oral medication.

Must have life expectancy of at least 12 weeks

Body weight ≥ 35 kg at screening 12. Willingness to adhere to the study treatment-specific contraception requirements: Patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of AZD4635 to prevent pregnancy in a female partner. Male patients must not donate or bank sperm for 24 weeks after treatment. Inclusion Criteria for Modules 1, 2, and 3:

Patients must have metastatic castrate resistant prostate cancer with histological or cytological confirmation. Patient may have bone-only metastatic disease.

Patients must have had either orchiectomy or be on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with testosterone > Patients must have previously received and progressed on ≥2 lines of approved systemic therapy for mCRPC, including a second generation hormonal agent (e.g., abiraterone, enzalutamide, or apalutamide)

Patients must have evidence of mCRPC that progressed within 6 months prior to screening according to one of the following: (a) PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment, where the PSA value at screening should be ≥ 1.0 ng/mL. (b) Radiographic disease progression in soft tissue based on RECIST Version 1.1 criteria with or without PSA progression. (c) Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression.

Exclusion Criteria

Exclusion Criteria for all Patients in all Modules:

History or presence of another primary invasive malignancy except for: malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of study drug and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease; localized non-invasive primary carcinoma under surveillance

Refractory nausea and vomiting, chronic gastrointestinal diseases, or previous significant small bowel resection that would preclude adequate absorption of AZD4635.

Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 21 days previously and there is no evidence of CNS disease progression or mild neurologic symptoms.

With the exception of alopecia, lymphopenia, and hypothyroidism, any unresolved toxicities from prior therapy greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) Grade 1 at the time of starting study treatment

Patients with prior ≥ Grade 3, serious, or life threatening immune-mediated reactions following prior anti-PD-1, anti-PD-L1, or other immuno-oncology therapies.

Prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months

Patients must have normotensive or well controlled blood pressure (> As judged by the Investigator or Medical Monitor, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B virus [known positive HBV surface antigen (HBsAg) result], hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies), or active hepatitis A. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Screening for chronic conditions is not required.

Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis, celiac disease, systemic lupus erythematous, Wegener's syndrome, myasthenia gravis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, autoimmune pneumonitis, autoimmune nephritis or nephropathy, etc.) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: a) vitiligo or alopecia, b) hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement, c) psoriasis or eczema not requiring systemic therapy for disease control, d) celiac disease controlled by diet alone.

Prior/concomitant therapy with AZD4635 or any other A2AR antagonist.

Ongoing corticosteroid use, at doses above physiologic replacement therapy. The following are exceptions to this criterion: a) use of intranasal, inhaled, topical orticosteroids, local steroid injections b) steroids as premedication for hypersensitivity reactions

Other exclusions apply

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