NCT06267729
Recruiting
Phase 1
A Phase I/II Open Label Study to Evaluate the Safety, Cellular Kinetics, and Efficacy of AZD0754, a Chimeric Antigen Receptor (CAR) T-cell Therapy Directed Against STEAP2, in Adult Participants With Metastatic Prostate Cancer: APOLLO
ConditionsMetastatic Prostate Cancer
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- AstraZeneca
- Enrollment
- 60
- Locations
- 15
- Primary Endpoint
- Incidence of participants with Dose-limiting Toxicity (DLTs)/DLT-like events, Adverse Events (AEs), including Adverse Events of Special Interest (AESIs) and Serious Adverse Events (SAEs).
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and antitumour activity of AZD0754 CAR T-cell therapy in participants with metastatic prostate cancer.
Detailed Description
This is a first-time in human, multi-center, open label, Phase I/II study of AZD0754 autologous CAR T-cell therapy administered intravenously to participants with metastatic prostate cancer. The study is intended to assess the safety, cellular kinetics, pharmacodynamics, preliminary efficacy, and feasibility of manufacturing AZD0754 for patients with metastatic prostate cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
Open-Label
Eligibility Criteria
- Ages
- 18 Years to 130 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participant must be 18 years or older at the time of signing the informed consent form.
- •Type of Participant and Disease Characteristics
- •Participants with:
- •A histologically confirmed diagnosis of metastatic adenocarcinoma of the prostate without known neuroendocrine differentiation or small cell features.
- •Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone analogue. Participants receiving medical castration therapy with gonadotropin releasing hormone analogues should continue this treatment during the study.
- •Measurable PSA \>/=1 ng/mL AND
- •Evidence of progression within 6 months prior to screening according to one of the following:
- •(i) Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumours Version 1.1 criteria with or without PSA progression as per Prostate Cancer Working Group Criteria 3 (PCWG3) (ii) Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan as per Prostate Cancer Working Group Criteria 3 (PCWG3).
- •(iii) Evidence of disease progression in bone according to PSMA PET scan results in tandem with PSA progression according to PCWG3 criteria."
- •Participant has previously received a NHA (ie, abiraterone, enzalutamide, apalutamide, darolutamide) and a taxane as part of their treatment for prostate cancer (whether before or in the metastatic castration-resistant setting). Participants who are ineligible for taxanes or refuse these therapies may be enrolled at the discretion of the investigator.
Exclusion Criteria
- •Participants with weight less than 39 kg
- •History of another primary malignancy except for malignancy treated with curative intent with no known active disease (≥ 2 years) before the first dose of study intervention and of low potential risk for recurrence. Such exceptions include non-melanoma cancer of the skin that has undergone curative therapy or adequately treated carcinoma in situ without evidence of disease.
- •Participants with known brain metastases.
- •Prior solid organ transplantation.
- •Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion:
- •Participants with vitiligo or autoimmune alopecia.
- •Participants with autoimmune hypothyroidism (eg, following Hashimoto thyroiditis) stable on hormone replacement.
- •Any chronic inflammatory or autoimmune 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 Sponsor.
- •Participants with coeliac disease controlled by diet alone.
Arms & Interventions
AZD0754
Experimental
AZD0754 monotherapy for treatment of participants with metastatic prostate cancer.
Intervention: AZD0754 (Biological)
AZD2287
Experimental
AZD2287 is a novel imaging agent for STEAP2
Intervention: AZD2287 (Biological)
Outcomes
Primary Outcomes
Incidence of participants with Dose-limiting Toxicity (DLTs)/DLT-like events, Adverse Events (AEs), including Adverse Events of Special Interest (AESIs) and Serious Adverse Events (SAEs).
Time Frame: Through study completion, an average of 2 years
Determine if treatment with AZD0754 is safe and tolerable through assessment of DLTs/DLT-like events, AEs, AESIs, SAEs, and changes from baseline in laboratory parameters, vital signs, and ECGs.
Secondary Outcomes
- Prostate-specific antigen (PSA) response rate - PSA50(Through study completion, an average of 2 years)
- Time to PSA Response (TTPSA50, TTPSA90)(Through study completion, an average of 2 years)
- Duration of PSA Response (DoPSA50, DoPSA90)(Through study completion, an average of 2 years)
- Duration of Response (DoR)(Through study completion, an average of 2 years)
- Pharmacokinetics - Exposure of AZD0754(Through study completion, an average of 2 years)
- Objective Response Rate (ORR)(Through study completion, an average of 2 years)
- Durable Response Rate (DRR)(Through study completion, an average of 2 years)
- Pharmacokinetics - time taken to reach maximum serum concentration (Tmax) of AZD0754(Through study completion, an average of 2 years)
- Biomarker - STEAP2 expression in Tumor(Through study completion, an average of 2 years)
- Durable PSA Response Rate (DRRPSA50, DRRPSA90)(Through study completion, an average of 2 years)
- Best Overall Response (BOR)(Through study completion, an average of 2 years)
- Disease Control Rate (DCR)(12 and 24 weeks after AZD0754 infusion)
- Pharmacokinetics - Last measurable serum concentration (Clast) of AZD0754(Through study completion, an average of 2 years)
- Pharmacokinetics - time of last measurable serum concentration (Tlast) of AZD0754(Through study completion, an average of 2 years)
- PSA response rate - PSA90(Through study completion, an average of 2 years)
- Time to PSA Progression (TTPSAP50, TTPSAP90)(Through study completion, an average of 2 years)
- Time to Response (TTR)(Through study completion, an average of 2 years)
- Percentage change in tumor size(Through study completion, an average of 2 years)
- Radiographic Progression-free Survival (rPFS)(Through study completion, an average of 2 years)
- Time from AZD0754 Infusion to the first Symptomatic Skeletal-related Events (SSRE)(Through study completion, an average of 2 years)
- Overall Survival (OS)(Through study completion, an average of 2 years)
- Pharmacokinetics - maximum observed serum concentration (Cmax) of AZD0754(Through study completion, an average of 2 years)
Investigators
Study Sites (15)
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