2025-524171-22-00招募中2 期
A Modular Open-label, Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Ascending Doses of AZD4956 as Monotherapy, and in Combination with Anti-Cancer Agents in Participants with Advanced/Metastatic Homologous Recombination Repair Defective Solid Tumours (PARTHENON)
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- For Part A (Dose Escalations) and Part B (Dose Expansion): • Incidence (%) of DLTs (for Part A only). • Incidence of AEs/SAEs (%). • Changes from baseline in physical examination, vital signs, ECGs, and laboratory findings. For Part B (Dose Expansion) Only:Radiological response evaluated according to RECIST v1.1 • PFS
研究概览
简要总结
Part A (Dose Escalations) and Part B (Dose Expansion): To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s) For Part B (Dose Expansion) Only: To assess the preliminary anti-tumour activity of AZD4956 in combination with anti-cancer agent(s)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- •Female participants must not breastfeed and must not donate or retrieve ova for their own use from screening to approximately 6 months after the last dose of study intervention.
- •Male participants: (a) Non-sterilised male participants who are sexually active with a female partner of child-bearing potential must use a male condom plus an additional contraceptive method during the study and for approximately 6 months after the last dose of study intervention. (b) Must refrain from fathering a child or donating sperm during the study and for approximately 6 months after the last dose of study intervention. (c) Female partners of male participants who are of child-bearing potential should use at least one highly effective method of contraception throughout this period.
- •Participants willing and able to comply with the study protocol for the duration of the study including undergoing study interventions and scheduled visits/examinations.
- •Ability to swallow oral medication intact and to retain it.
- •Module 1 Part A: Demonstrated evidence of disease progression, via imaging, during or following standard therapy known to provide clinical benefit for their condition.
- •Module 1 Part A: Participants must have advanced or metastatic solid tumours and are required to have a local genomic testing result, as specified in the protocol Note: Participants with stromal, sex cord or germ cell tumours are excluded. Participants with carcinosarcoma are eligible.
- •Module 1 Part A: Participants may have received up to one prior line of therapy with a PARPi-based regimen (either as a treatment or as maintenance).
- •Module 2 Part A and Part A-PD: Participants must have evaluable disease as described in the study protocol.
- •Module 2 Part A and Part A-PD: Participants in PD backfill cohorts must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance). For participants in dose escalation cohorts, one prior line of therapy with a PARPi-based regimen (either as a treatment or as maintenance) is allowed but not required.
- •Module 2 Part A and Part A-PD: In the opinion of the investigator, participants must be suitable for treatment with a PARPi.
- •Consent to provide adequate baseline tumour sample prior to start of treatment, as applicable per module-specific criteria.
- •Module 2 Part A-Non-PD and Part B:Participants must have documented metastatic disease by clear evidence of ≥ 1 bone lesion (defined as one lesion with positive uptake on bone scan) and/or ≥ 1 soft tissue lesion (measurable or non-measurable).
- •Module 2 Part A-Non-PD and Part B: Participants must have received the following prior approved systemic therapies for metastatic prostate cancer: at least one but no more than 2 prior ARPIs and, if applicable, at least one but no more than 2 prior taxane-based chemotherapies (regardless of whether in hormone-sensitive prostate cancer or CRPC settings). Participants who are not amenable to chemotherapy (unfit, intolerant, participant choice) or to other standard therapies (where available), or for whom no therapy of proven efficacy exists for mCRPC may also be considered, provided it is documented that they were informed about all therapeutic options, or 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.
- •Module 2 Part A-Non-PD and Part B: Participants must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).
- •Participants must be ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), at the time of signing the ICF.
- •Documented locally advanced or metastatic solid tumour malignancy. For further specification, please refer to the individual modules.
- •ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to screening and first day of dosing.
- •Minimum life expectancy ≥ 12 weeks, as judged by the investigator.
- •Adequate organ and marrow function.
- •Male and/or female, as assigned at birth, inclusive of all gender identities.
- •Female participants of child-bearing potential: (a) Must have a negative pregnancy test result at screening and prior to each cycle of study intervention. (b) If sexually active with a non-sterilised male partner, must use at least one highly effective method of birth control plus a barrier method (eg, condom with spermicide, in accordance with local guidelines) from screening to approximately 6 months after the last dose of study intervention. Note: The use of hormonal contraceptive methods is not permitted in this study for female participants of child-bearing potential.
排除标准
- •Any significant laboratory finding or any severe and uncontrolled medical condition, including but not limited to uncontrolled hypertension, bleeding diathesis, hepatic failure, unstable respiratory or cardiac conditions, active interstitial lung disease, active bacterial, viral, fungal or other infection requiring treatment, which in the investigator’s opinion makes it undesirable or pose a safety risk for the participant to participate in the study.
- •Active gastrointestinal disease or other condition that will interfere significantly with the swallowing, absorption, distribution, metabolism or excretion of oral therapy.
- •History of another primary malignancy except for: (a) Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. (b) Adequately treated non melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease. (d) Locally non-invasive primary under surveillance (eg, basal cell carcinoma of the skin).
- •Participants with history of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
- •Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy, excluding alopecia. Note: Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).
- •Prohibited concomitant therapies are listed in the protocol. Adequate treatment wash-out periods are listed in the study protocol. Inability to stop the use thereof, at least 21 days or at least 5 half-lives (whichever is longer) before the first dose of study intervention until 30 days after the last dose of study intervention.
- •Concomitant medications known to prolong QTc should be used with caution and cannot be used starting with the first dose of study intervention and through the DLT review period or during the scheduled ECG assessments.
- •Any concurrent anti-cancer treatment. Note: Concurrent use of hormonal therapy for non cancer-related conditions (eg, hormone replacement therapy) is allowed.
- •Participants with a known hypersensitivity to the investigational product(s) or any of the excipients of the product(s).
- •Module 2 Part A (Non-PD Backfill Cohorts) and Part B (Dose Expansion Cohorts): Participants who are unevaluable for both bone and soft tissue progression as defined by meeting both of the following criteria: (a) A bone scan referred to as a superscan showing an intense symmetric activity in the bones and no or limited technetium excretion by the kidneys, and (b) No soft tissue lesion (measurable or non-measurable) that can be assessed by RECIST v1.1 criteria.
- •Participants with any known predisposition to bleeding (eg, active peptic ulceration, proliferative diabetic retinopathy).
- •Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease. Note: Participants with asymptomatic, radiographically stable brain metastases and not requiring steroids for symptomatic management will be eligible, as well as participants who have completed definitive therapy, are not on steroids, and have a stable neurologic status for at least 4 weeks prior to start of study intervention.
- •Allogenic organ transplantation.
- •Participants with any of the cardiac criteria described in the protocol.
- •Other cardiovascular diseases as defined in the protocol.
- •Known to have active infection, including hepatitis B virus (HBV) or hepatitis C virus (HCV). Screening for chronic conditions is not required.
- •Known history of infection with HIV. Screening for HIV is not required.
- •Any history of persisting (> 2 weeks) severe pancytopaenia due to any cause (eg, ANC < 0.5 × 10^9/L or platelets < 50 × 10^9/L).
结局指标
主要结局
For Part A (Dose Escalations) and Part B (Dose Expansion): • Incidence (%) of DLTs (for Part A only). • Incidence of AEs/SAEs (%). • Changes from baseline in physical examination, vital signs, ECGs, and laboratory findings. For Part B (Dose Expansion) Only:Radiological response evaluated according to RECIST v1.1 • PFS
For Part A (Dose Escalations) and Part B (Dose Expansion): • Incidence (%) of DLTs (for Part A only). • Incidence of AEs/SAEs (%). • Changes from baseline in physical examination, vital signs, ECGs, and laboratory findings. For Part B (Dose Expansion) Only:Radiological response evaluated according to RECIST v1.1 • PFS
次要结局
- Efficacy: Radiological response evaluated according to RECIST v1.1 as described in the protocol. PK: Plasma concentrations of AZD4956 and plasma PK parameters, Urine PK parameters of AZD4956, as data permits. PD: Assessment of biomarker in tumour cells at baseline and during treatment.
- Module 2: PK: Plasma concentrations of saruparib and plasma PK parameters, including but not limited to AUC, Cmax, and tmax as data allow
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (3)
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