A Modular Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0516 as Monotherapy and in Combination with Anti-cancer Agents in Participants with Metastatic Prostate Cancer.

AstraZeneca AB6 个研究点分布在 1 个国家目标入组 38 人2025年12月12日

概览

阶段: 1/2 期
干预措施: 未指定
疾病 / 适应症: 未指定
发起方: AstraZeneca AB
入组人数: 38
试验地点: 6
主要终点: Dose Escalation (Part A) - Safety: Incidence of AEs, AESIs, SAEs. Incidence of DLTs. Rate of AZD0516 discontinuation due to toxicity. Clinically significant changes from baseline in laboratory parameters, vital signs, ECGs, ECOG performance status, and physical examination.
状态: 尚未招募
最后更新: 4个月前

概览研究者入排标准结局指标研究点相似试验

概览

简要总结

Dose Escalation (Part A) Safety To assess the safety and tolerability and to determine the MTD and/or RDE(s) of AZD0516 as monotherapy and in combination with anti-cancer agents. Dose Optimisation (Part B) Efficacy To assess the preliminary antitumour activity of AZD0516 as monotherapy and in combination with anti-cancer agents. Dose Optimisation (Part B) Safety To assess the safety and tolerability of AZD0516 as monotherapy and in combination with anti-cancer agents. Efficacy Expansion (Part C) Efficacy To assess the anti-tumour activity of AZD0516 as monotherapy and/or in combination with other anti-cancer agents.

注册库

euclinicaltrials.eu

开始日期

2025年12月12日

结束日期

待定

最后更新

4个月前

性别

Male

研究者

发起方

AstraZeneca AB

责任方

Principal Investigator

主要研究者

AstraZeneca Clinical Study Information Center

Scientific

AstraZeneca AB

入排标准

入选标准

•Informed Consent - Capable of giving signed informed consent as described in the study protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
•Type of Participant and Disease Characteristics - ECOG performance status of 0 or
•Type of Participant and Disease Characteristics - Life expectancy of at least 12 weeks in the opinion of the investigator.
•Type of Participant and Disease Characteristics - Adequate organ and marrow function in the absence of blood transfusion or growth factor support (within 21 days prior to the scheduled first dose of study intervention as indicated in the study protocol).
•Type of Participant and Disease Characteristics - Participants must have received and progressed on, are refractory or are intolerant to standard therapy in accordance with local practice for their stage of disease or, in the opinion of the investigator, a clinical study is the best option for the participant’s next treatment based on response and/or tolerability to prior therapy. Participants with contraindications, to standard of care therapy, may also be considered if it is documented, and they have been informed about all therapeutic options.
•Sex and Contraceptive/Barrier Requirements - Male, as assigned at birth, inclusive of all gender identities: (a) Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. (b) Participants who are sexually active with a female partner of childbearing potential, including a pregnant partner, must use a male condom (and add spermicide, if available) while on study and for an appropriate period after final dose of study intervention. (i) Investigators are to advise participants about the preservation of sperm prior to AZD
•(ii) It is strongly recommended for the female partner of a male participant to also use a highly effective method of contraception throughout this period, as described below: Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study interventions [periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception]), a vasectomised partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™, Xulane™, or NuvaRing®.
•Sex and Contraceptive/Barrier Requirements - Participants must refrain from sperm donation while on study and for an appropriate period following the last dose of study intervention.
•Informed Consent - Consent to provide adequate baseline tumour sample prior to start of treatment, as applicable per module-specific criteria.
•Informed Consent - Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional Genomics Initiative research that supports the Genomic Initiative (see study protocol). Participants who do not provide informed consent for Optional Genetic Research may still be enrolled in the study.

排除标准

•Medical Conditions - Cancer related spinal cord compression, or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to study enrolment. Any participant at high risk of cord compression based on imaging at screening should have the bone lesions treated prior to study enrolment. A scan to confirm the absence of brain metastases is not required.
•Medical Conditions - History of non-infectious ILD/pneumonitis that has required oral or intravenous steroids, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening (findings from screening CT/HRCT if available).
•Medical Conditions - Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement or prior pneumonectomy or require supplemental oxygen (including intermittent or discretionary use).
•Medical Conditions - Participants with MDS/AML or with features suggestive of MDS/AML.
•Prior/Concomitant Therapy - Previous treatment with a STEAP2 targeting modality.
•Prior/Concomitant Therapy - Previous treatment with a chemotherapeutic agent or ADC that inhibits TOP1 activity.
•Prior/Concomitant Therapy - Any concomitant medications or herbal supplements known to be strong inhibitors of metabolic enzymes. The required washout period prior to starting study intervention is at least 21 days or 5 half-lives, whichever is longer.
•Prior/Concomitant Therapy - Treatment with any of the following agents and interventions: (a) Any other anti-cancer agents within the following time periods prior to the first dose of study intervention (i) Cytotoxic treatment: 21 days. (ii) Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is longer). (iii) Biological products including immuno-oncology agents: 28 days. (iv) Any investigational agents or study interventions from a previous clinical study: 28 days or 5 half-lives (whichever is longer). (b) Radiotherapy: Participants who have received wide field of radiation (including whole brain radiotherapy) within 28 days prior to the first dose of study intervention or limited field radiotherapy (including stereotactic radiotherapy or gamma-knife) for palliative intent within 14 days prior to the first dose of study intervention. Participants who have not recovered from radiotherapy-related toxicity to Grade 1 or baseline will not be eligible. (c) Major surgery (as defined by the investigator): Within 28 days prior to the first dose of study intervention. (d) Chloroquine/hydroxychloroquine: At least 14 days prior to the first dose of study intervention.
•Prior/Concomitant Therapy - Any concurrent anti-cancer treatment except for GnRH modulators, which should be continued throughout the study (unless bilateral orchiectomy). Participants on a stable bisphosphonate or denosumab regimen are eligible.
•Prior/Concomitant Therapy - Any concomitant medications known to prolong QTc and/or have a known risk for TdP should not be combined with AZD

结局指标

主要结局

Dose Escalation (Part A) - Safety: Incidence of AEs, AESIs, SAEs. Incidence of DLTs. Rate of AZD0516 discontinuation due to toxicity. Clinically significant changes from baseline in laboratory parameters, vital signs, ECGs, ECOG performance status, and physical examination.

Dose Optimisation (Part B) and Efficacy Expansion (Part C) - Efficacy: PSA50 response rate.

Dose Optimisation (Part B) - Safety: Incidence of AEs, AESIs, SAEs. Rate of AZD0516 discontinuation due to toxicity. Clinically significant changes from baseline in laboratory parameters, vital signs, ECGs, ECOG perform.

次要结局

Dose Escalation (Part A) Dose Optimisation (Part B) Efficacy Expansion (Part C)-Efficacy-PSA related endpoints: PSA50 response rate(Part A), PSA90 response rate, Time to PSA50 response, Time to PSA90 response, Duration of PSA50 response, Duration of PSA90 response, Durable PSA50 response rate, Durable PSA90 response rate, Time to PSA progression, and PSA over time.
Dose Escalation (Part A) Dose Optimisation (Part B) Efficacy Expansion (Part C)-Efficacy:Radiological response endpoints and estimands, assessed by the investigator evaluated according to RECIST v1.1 (soft tissue) and PCWG3 (bone) criteria: ORR, BOR, DoR, DRR, DCR, TTR, percentage change in tumour size, and rPFS. Other efficacy endpoint: OS
Dose Escalation (Part A) and Dose Optimisation (Part B) - Pharmacokinetics: Plasma concentration of AZD0516, total antibody (conjugated and unconjugated) and total unconjugated warhead. Plasma PK parameters of AZD0516, total antibody (conjugated and unconjugated) and including but not limited to AUC, Cmax, tmax, clearance, and t1/2, as data allow.
Dose Escalation (Part A) and Dose Optimisation (Part B) - Biomarker:Target expression via STEAP2 IHC on treatment versus at baseline (in paired biopsy cohorts). Evaluate association of STEAP2 expression with AZD0516 response.
Dose Escalation (Part A) and Dose Optimisation (Part B) - Immunogenicity: Evaluate the number and percentage of participants who develop ADA.
Efficacy Expansion (Part C) - Safety:Incidence of AEs, AESIs, SAEs. Rate of AZD0516 discontinuation due to toxicity. Clinically significant changes from baseline in laboratory parameters, vital signs, ECGs, ECOG performance status, and physical examination.