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).

Phase 2

Withdrawn

• Conditions: Progressive Metastatic Castrate-Resistant Prostate Cancer - Prostate cancer; 10027476

• Registration Number: NL-OMON51202
• Lead Sponsor: Astra Zeneca

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

Inclusion Criteria

Age
1 Participant must be 18 years of age inclusive at the time of signing the
informed consent.
Type of Participant and Disease Characteristics
2 Histologically confirmed adenocarcinoma of the prostate
* Disease must be metastatic and inoperable and for which there is no curative
intervention available. Participants may have bone-only disease.
* Participants presenting with treatment-emergent neuroendocrine
differentiation, but not primary small-cell features, are eligible.
3 Known castrate-resistant disease, defined as:
* Testosterone level in the castration range (levels < 50 ng/dl) because of a
previous, and ongoing, androgen-deprivation with luteinizing hormone-releasing
hormone (LHRH) agonists or antagonists or bilateral orchiectomy. Participants
must have developed progression of metastases following surgical castration or
during medical androgen ablation therapy. Participants receiving medical
castration therapy with gonadotropin-releasing hormone (GnRH) analogues should
continue this treatment during this study.
4 Evidence of disease progression * 6 months defined by one or more of the
following:
* Progression as defined by RECIST v1.1 criteria for assessment of malignant
soft tissue disease and lymph nodes
* Progression of bone lesions on bone scan from a previous or baseline
assessment per PCWG3
* Rising PSA defined as at least two consecutive rises in PSA to be documented
over a reference value (measure 1) taken at least 1 week apart. The first
rising PSA (measure 2) should be taken at least 7 days after the reference
value. A third confirmatory PSA measure is required (2nd and beyond the
reference level) to be greater than the second measure and it must be obtained
at least 7 days after the 2nd measure. If this is not the case, a fourth PSA
measure is required to be taken and be greater than 2nd measure. The third (or
the fourth) confirmatory PSA should be taken within 4 weeks prior to study
entry.
5 Must have measurable disease:
* 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 is
suitable for repeated measurement
Or
* Non-measurable disease must have measurable PSA * 1.0 ng/mL as the minimum
starting level for trial entry if the confirmed rise is the only indication of
progression (excluding small cell carcinoma).

Weight
6 Body weight > 30 kg at screening.

Reproduction
7 Willingness to adhere to the study treatment-specific contraception
requirements: Participants must be surgically sterile or using an acceptable
method of contraception (defined as a male condom in conjunction with
spermicides) for the duration of the study (from the time they sign ICF) and
for 12 weeks (3 months) after the last dose of AZD4635 and/or durvalumab and
for 24 weeks (6 months) after the last dose of cabazitaxel to prevent pregnancy
in a female partner. Participants must not donate or bank sperm for 24 weeks
after treatment. The reporting of any pregnancy in the female partner of a
participant is described in Section 8.3.9.1 of the protocol.

Bone Marrow Reserve and Organ Function
8 Adequate bone marrow reserve and organ function as demonstrated by all of the
following laboratory values:
* Absolute neut

Exclusion Criteria

Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:

Medical Conditions
1 Active brain metastases or leptomeningeal metastases. Participants with brain
metastases are eligible if treated and there is no evidence of progression for
at least 8 weeks after treatment is completed and within 28 days prior to the
first dose of study intervention.
2 There must be no requirement for immunosuppressive doses of systemic
corticosteroids (> 10 mg/day prednisone/equivalent) for at least 2 weeks prior
to study enrollment. For current or prior use of immunosuppressive medication
within 14 days before the first dose the following will be exceptions to this:
* Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra-articular injection)
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
* Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
3 Participant with a history of pneumonitis.
4 History of a second malignancy that is progressing and/or received active
treatment * 3 years before the first dose of study intervention.
5 As judged by the Investigator, any evidence of severe or uncontrolled
systemic diseases, including uncontrolled hypertension, active bleeding
diatheses, active infection including hepatitis B, hepatitis C, and human
immunodeficiency virus, chronic gastrointestinal diseases (e.g., Crohn's
disease, chronic colitis), ongoing or active infection, symptomatic congestive
heart failure, uncontrolled hypertension, unstable angina pectoris,
uncontrolled cardiac arrhythmia, or active interstitial lung disease (ILD).
Screening for chronic conditions is not required.
6 Creatinine clearance < 50 mL/min (calculated by Cockcroft-Gault equation).
7 Prior exposure to immune-mediated therapy including, but not limited to
anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies, excluding
therapeutic anti-cancer vaccines.
8 History of allogeneic organ transplantation.
9 Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis
[with the exception of diverticulosis], systemic lupus erythematosus,
Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis,
Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The
following are exceptions to this criterion:
* Participants with vitiligo or alopecia
* Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable
on hormone replacement
* Any chronic skin condition that does not require systemic therapy
* Participants without active disease in the last 5 years may be included but
only after consultation with the Study Physician
* Participants with coeliac disease controlled by diet alone
10 History of active primary immunodeficiency.
11 Active infection including tuberculosis (clinical evaluation that may
include clinical history, physical examination and radiographic findings, and
tuberculosis testing in line with local practice).
12 Receipt of live attenuated vaccine within 30 days prior to the first dose of
study intervention.

Additional Exclusion Criteria Specific for Arm B: Medical Conditions
13 Participant w

Study & Design

• Study Type: Interventional
• Study Design: Not specified