[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07446855":3,"trial-entities:NCT07446855":291,"trial-summary:NCT07446855":302},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":25,"primary_purpose":26,"phases":27,"enrollment_info":30,"interventions":33,"primary_outcomes":49,"secondary_outcomes":61,"sex":130,"minimum_age":131,"maximum_age":132,"healthy_volunteers":15,"eligibility_criteria":133,"std_ages":162,"locations":165,"central_contacts":282,"overall_officials":288,"references":289,"see_also_links":290},"NCT07446855","D8570C00001","Study of AZD4956 as Monotherapy and in Combination With Anti-Cancer Agents in Participants With Advanced\u002FMetastatic Homologous Recombination Deficient Solid Tumours","A Modular Open-label, Phase I\u002FIIa 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\u002FMetastatic Homologous Recombination Repair Defective Solid Tumours","RECRUITING","2030-03-29","2026-08","2026-08-11","2026-03-17","AstraZeneca","INDUSTRY",false,"The purpose of this modular, first trial in human study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of ascending dose levels (DLs) of AZD4956 monotherapy and in combination with other anti-cancer agents in participants with advanced\u002Fmetastatic solid tumours with homologous recombination repair (HRR) deficiencies.","The study consists of individual modules each evaluating the safety and tolerability of AZD4956 dosed as monotherapy, or with a specific combination partner. There are following 2 modules -\n\n1. Module 1: AZD4956 monotherapy\n2. Module 2: AZD4956 in combination with saruparib\n\nEach module may further contain 2 parts-\n\n* Part A (dose escalation\u002Fdose finding): To determine the safety, tolerability, PK, PD, and preliminary efficacy of AZD4956 as monotherapy or in combination.\n* Part B (dose expansion): To further evaluate the safety and preliminary efficacy of AZD4956 in combination with other anti-cancer agents.",[19],"Solid Tumours",[21,22,23,24],"Advanced\u002Fmetastatic homologous recombination repair defective solid tumours","Poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi)","Pharmacokinetics","Pharmacodynamics","INTERVENTIONAL","TREATMENT",[28,29],"PHASE1","PHASE2",{"count":31,"type":32},180,"ESTIMATED",[34,44],{"type":35,"name":36,"description":37,"armGroupLabels":38},"DRUG","AZD4956","AZD4956 will be administered orally.",[39,40,41,42,43],"Module 1 Part A: AZD4956 monotherapy (Dose escalation)","Module 2 Part A Optional PD backfill cohort: AZD4956 + saruparib","Module 2 Part A Optional non-PD backfill cohort: AZD4956 + saruparib","Module 2 Part A: AZD4956 + saruparib (Dose escalation)","Module 2 Part B: AZD4956 + saruparib (Dose expansion)",{"type":35,"name":45,"description":46,"armGroupLabels":47},"Saruparib","Saruparib will be administered orally.",[40,48,41,42,43],"Module 2 Part A Optional PD backfill cohort: Saruparib monotherapy",[50,54,58],{"measure":51,"description":52,"timeFrame":53},"Parts A and B: Number of participants with adverse events (AEs) and serious adverse events (SAEs)","To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s).","From Screening (Day -28) to follow-up (up to 3.5 years)",{"measure":55,"description":56,"timeFrame":57},"Part B: Progression free survival (PFS)","PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression.","Up to 3.5 years",{"measure":59,"description":52,"timeFrame":60},"Part A - Number of participants with dose-limiting toxicities (DLTs)","Up to 28 days",[62,65,68,71,74,77,80,82,85,89,91,94,97,101,104,107,111,115,117,119,122,124,126],{"measure":63,"description":64,"timeFrame":57},"Objective response (OR)","OR is defined as if a participant achieves a best overall response (BOR) of confirmed complete response (CR) or partial response (PR), as assessed by the investigator, according to response evaluation criteria in solid tumours (RECIST) v1.1 criterion.",{"measure":66,"description":67,"timeFrame":57},"Duration of response (DoR)","DoR is defined as the time from the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by prostate cancer working group 3 (PCWG3), until the date of documented disease progression or death in the absence of disease progression.",{"measure":69,"description":70,"timeFrame":57},"Best Overall Response (BOR)","To assess the preliminary anti-tumour activity of AZD4956 monotherapy and in combination with anti-cancer agent(s).",{"measure":72,"description":73,"timeFrame":57},"Time to response (TTR)","TTR is defined as the time from the date of first dose of study intervention until the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3, which is subsequently confirmed.",{"measure":75,"description":76,"timeFrame":57},"Disease control (DC)","DC is defined as if a participant has achieved a best OR of confirmed CR or PR or SD as BOR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3.",{"measure":78,"description":79,"timeFrame":57},"Clinical benefit rate (CBR)","CBR is defined as the percentage of advanced cancer participants who achieve CR, PR, or at least 16 weeks\u002F24 weeks of stable disease, assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3, as a result of therapy.",{"measure":81,"description":56,"timeFrame":57},"Part A: Progression free survival (PFS)",{"measure":83,"description":84,"timeFrame":57},"Percentage change from baseline in tumour size","The best percentage change from baseline in target lesion (TL) tumour size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST v1.1 assessments.",{"measure":86,"description":87,"timeFrame":88},"Number of participants with cancer antigen 125 (CA125) response (for ovarian cancer participants)","CA125 response is defined as if at least a 50% reduction in CA125 levels from a pre-treatment sample.","From baseline up to 3.5 years",{"measure":90,"description":56,"timeFrame":57},"Radiological progression free survival (rPFS) (for prostate cancer participants)",{"measure":92,"description":93,"timeFrame":88},"Change from baseline in prostate specific antigen 50 (PSA50) response rate (for prostate cancer participants)","PSA50 response is defined as if a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later has been achieved.",{"measure":95,"description":96,"timeFrame":88},"Change from baseline in PSA90 response rate (for prostate cancer participants)","PSA90 response is defined as if a ≥ 90% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later has been achieved.",{"measure":98,"description":99,"timeFrame":100},"Change from baseline in PSA undetectable rate","Undetectable PSA is defined as a measurement of \\\u003C 0.2 ng\u002FmL.","At 3, 6 and 9 months",{"measure":102,"description":103,"timeFrame":57},"Time to PSA50\u002F90 response (for prostate cancer participants)","Time to PSA50\u002F90 response is defined as the time from the date of first dose of study intervention until the date of first documented PSA response (≥ 50%\u002F90% decrease in PSA from baseline) that is confirmed by a second consecutive PSA assessment at least 3 weeks later.",{"measure":105,"description":106,"timeFrame":57},"Time to PSA progression (for prostate cancer participants)","Time to PSA progression is defined as the time from date of first dose of study intervention until the date of first documented PSA progression or the last PSA result in the absence of progression.",{"measure":108,"description":109,"timeFrame":110},"PSA PFS at 6 months (PSA-6)","PSA progression is defined as an increase in PSA of ≥ 25% from the nadir and an absolute increase of at least 2 ng\u002FmL above nadir beyond 12 weeks. To assess the preliminary anti-tumour activity of AZD4956 monotherapy and in combination with anti-cancer. agent(s)","At 6 months",{"measure":112,"description":113,"timeFrame":114},"Area under the concentration-time curve (AUC)","To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s).","From date of first dose of study intervention up to 59 days after first dose",{"measure":116,"description":113,"timeFrame":114},"Maximum concentration (Cmax)",{"measure":118,"description":113,"timeFrame":114},"Time to maximum concentration (Tmax)",{"measure":120,"description":113,"timeFrame":121},"Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe(t1-t2))","From date of first dose of study intervention up to 16 days after first dose",{"measure":123,"description":113,"timeFrame":121},"Renal clearance (CLR)",{"measure":125,"description":113,"timeFrame":121},"Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 (Ae(t1-t2))",{"measure":127,"description":128,"timeFrame":129},"Change in amount of KRAB-associated protein-1 phosphorylated on serine 824 [pKAP1 (Ser824)] biomarker in tumour cells at baseline and during treatment","To evaluate PD of AZD4956 in tumour cells when given orally as monotherapy and in combination with anti-cancer agent(s).","From Baseline up to 3.5 years","ALL","18 Years","130 Years",{"inclusion":134,"exclusion":150,"raw_text":161},[135,136,137,138,139,140,141,142,143,144,145,146,147,148,149],"Documented locally advanced or metastatic solid tumour malignancy.","Eastern cooperative oncology group (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.","Adequate organ and marrow function.","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.","Demonstrated evidence of disease progression.","Participants must have advanced or metastatic solid tumours.","Participants may have received up to one prior line of therapy with a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi)-based regimen (either as a treatment or as maintenance).","Participants must have one of the following conditions-","Participants must have evaluable disease.","Participants in PD backfill cohorts must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).","Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and advanced\u002Fmetastatic CRPC.","Participants must have documented metastatic disease by clear evidence of ≥ 1 bone lesion (defined as one lesion with positive uptake on bone scan) and\u002For ≥ 1 soft tissue lesion (measurable or non-measurable).","Participants must have received the prior approved systemic therapies for metastatic prostate cancer.","Participants must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).",[151,152,153,154,155,156,157,158,159,160],"Any significant laboratory finding or any severe and uncontrolled medical condition.","Participants with any known predisposition to bleeding.","Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease.","Allogenic organ transplantation.","Known to have active infection, including hepatitis B virus (HBV) or hepatitis C virus (HCV).","Known history of infection with human immunodeficiency virus (HIV).","Active gastrointestinal disease or other condition that will interfere significantly with the swallowing, absorption, distribution, metabolism or excretion of oral therapy.","Participants with history of myelodysplastic syndrome (MDS)\u002Facute myeloid leukaemia (AML) or with features suggestive of MDS\u002FAML.","Participants with a known hypersensitivity to the investigational product(s) or any of the excipients of the product(s).","Previous dosing with AZD4956.","Core Inclusion Criteria:\n\n* Documented locally advanced or metastatic solid tumour malignancy.\n* Eastern cooperative oncology group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to screening and first day of dosing.\n* Minimum life expectancy ≥ 12 weeks.\n* Adequate organ and marrow function.\n* 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.\n\nModule 1 Inclusion Criteria:\n\n* Demonstrated evidence of disease progression.\n* Participants must have advanced or metastatic solid tumours.\n* Participants may have received up to one prior line of therapy with a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi)-based regimen (either as a treatment or as maintenance).\n\nModule 2 Inclusion Criteria:\n\nPart A (AZD4956 in Combination with Saruparib Dose Escalation) and Part A-PD (PD Backfill Cohorts):\n\n* Participants must have one of the following conditions-\n\n  1. Histologically or cytologically confirmed carcinoma of the breast with recurrent locally advanced or metastatic disease and evidence of a predicted loss of function germline or somatic mutation.\n  2. Histologically or cytologically confirmed advanced ovarian, fallopian tube, or primary peritoneal cancer.\n  3. Histologically or cytologically confirmed adenocarcinoma of the prostate and advanced\u002Fmetastatic castrate resistant prostate cancer (CRPC).\n  4. Histologically or cytologically confirmed advanced\u002Fmetastatic pancreatic cancer.\n* Participants must have evaluable disease.\n* Participants in PD backfill cohorts must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).\n\nPart A (PD Backfill Cohorts) - Participants Undergoing Paired Biopsies:\n\n\\- Participants must have a tumour suitable for biopsy.\n\nPart A-Non-PD (Non-PD Backfill Cohorts) and Part B (Dose Expansion Cohorts):\n\n* Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and advanced\u002Fmetastatic CRPC.\n* Participants must have documented metastatic disease by clear evidence of ≥ 1 bone lesion (defined as one lesion with positive uptake on bone scan) and\u002For ≥ 1 soft tissue lesion (measurable or non-measurable).\n* Participants must have received the prior approved systemic therapies for metastatic prostate cancer.\n* Participants must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).\n\nCore Exclusion Criteria:\n\n* Any significant laboratory finding or any severe and uncontrolled medical condition.\n* Participants with any known predisposition to bleeding.\n* Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease.\n* Allogenic organ transplantation.\n* Known to have active infection, including hepatitis B virus (HBV) or hepatitis C virus (HCV).\n* Known history of infection with human immunodeficiency virus (HIV).\n* Active gastrointestinal disease or other condition that will interfere significantly with the swallowing, absorption, distribution, metabolism or excretion of oral therapy.\n* Participants with history of myelodysplastic syndrome (MDS)\u002Facute myeloid leukaemia (AML) or with features suggestive of MDS\u002FAML.\n* Participants with a known hypersensitivity to the investigational product(s) or any of the excipients of the product(s).\n* Previous dosing with AZD4956.",[163,164],"ADULT","OLDER_ADULT",[166,174,182,189,196,203,209,216,222,229,232,239,242,245,251,257,263,270,276],{"facility":167,"status":8,"city":168,"state":168,"zip":169,"country":170,"geoPoint":171},"Research Site","New York","10065","United States",{"lat":172,"lon":173},40.71427,-74.00597,{"facility":167,"status":175,"city":176,"state":177,"zip":178,"country":170,"geoPoint":179},"NOT_YET_RECRUITING","Providence","Rhode Island","02903",{"lat":180,"lon":181},41.82399,-71.41283,{"facility":167,"status":8,"city":183,"state":184,"zip":185,"country":170,"geoPoint":186},"Houston","Texas","77030",{"lat":187,"lon":188},29.76328,-95.36327,{"facility":167,"status":8,"city":190,"state":191,"zip":192,"country":170,"geoPoint":193},"Fairfax","Virginia","22031",{"lat":194,"lon":195},38.84622,-77.30637,{"facility":167,"status":8,"city":197,"zip":198,"country":199,"geoPoint":200},"Melbourne","3000","Australia",{"lat":201,"lon":202},-37.814,144.96332,{"facility":167,"status":175,"city":204,"zip":205,"country":199,"geoPoint":206},"Westmead","2145",{"lat":207,"lon":208},-33.80383,150.98768,{"facility":167,"status":175,"city":210,"zip":211,"country":212,"geoPoint":213},"Chūōku","104-0045","Japan",{"lat":214,"lon":215},33.63867,130.67068,{"facility":167,"status":8,"city":217,"zip":218,"country":212,"geoPoint":219},"Kashiwa","277-8577",{"lat":220,"lon":221},35.86224,139.97732,{"facility":167,"status":175,"city":223,"zip":224,"country":225,"geoPoint":226},"Seoul","03080","South Korea",{"lat":227,"lon":228},37.566,126.9784,{"facility":167,"status":175,"city":223,"zip":230,"country":225,"geoPoint":231},"120-752",{"lat":227,"lon":228},{"facility":167,"status":175,"city":233,"zip":234,"country":235,"geoPoint":236},"Barcelona","08023","Spain",{"lat":237,"lon":238},41.38879,2.15899,{"facility":167,"status":175,"city":233,"zip":240,"country":235,"geoPoint":241},"08036",{"lat":237,"lon":238},{"facility":167,"status":175,"city":233,"zip":243,"country":235,"geoPoint":244},"8035",{"lat":237,"lon":238},{"facility":167,"status":175,"city":246,"zip":247,"country":235,"geoPoint":248},"Logroño","26006",{"lat":249,"lon":250},42.46615,-2.45115,{"facility":167,"status":175,"city":252,"zip":253,"country":235,"geoPoint":254},"Pozuelo de Alarcón","28223",{"lat":255,"lon":256},40.43293,-3.81338,{"facility":167,"status":175,"city":258,"zip":259,"country":235,"geoPoint":260},"Seville","41013",{"lat":261,"lon":262},37.38283,-5.97317,{"facility":167,"status":175,"city":264,"zip":265,"country":266,"geoPoint":267},"Cambridge","CB2 0QQ","United Kingdom",{"lat":268,"lon":269},52.2,0.11667,{"facility":167,"status":175,"city":271,"zip":272,"country":266,"geoPoint":273},"London","SE1 9RT",{"lat":274,"lon":275},51.50853,-0.12574,{"facility":167,"status":175,"city":277,"zip":278,"country":266,"geoPoint":279},"Sutton","SM25PT",{"lat":280,"lon":281},51.35,-0.2,[283],{"name":284,"role":285,"phone":286,"email":287},"AstraZeneca Clinical Study Information Center","CONTACT","1-877-240-9479","information.center@astrazeneca.com",[],[],[],{"nct_id":4,"conditions":292,"biomarkers":300},[293,294,295,296,297,298,299],"Breast Carcinoma","Fallopian Tube Carcinoma","Malignant Ovarian Neoplasm","Pancreatic Carcinoma","Primary Peritoneal Cancer","Prostate Carcinoma","Solid Neoplasm",[301],"AHRR Gene",{"nct_id":4,"found":303,"summary":304,"prompt_version":314},true,{"design":305,"status":306,"heading":307,"summary":308,"follow_up":309,"word_count":310,"commitments":311,"compensation":312,"drugs_mentioned":313},"This study is designed in modules, with some parts testing AZD4956 alone and others testing it with Saruparib. It will involve up to 180 participants.","completed","Study of AZD4956 for Advanced Solid Tumors","This study is testing a new medication called AZD4956, both by itself and in combination with another anti-cancer drug called Saruparib. We are looking for people with advanced or metastatic (spread to other parts of the body) solid tumors that have specific genetic changes called homologous recombination repair (HRR) deficiencies. The main goals are to understand how safe AZD4956 is, what side effects it might cause, and if it helps to slow down or stop cancer growth. We will be looking at how long people live without their cancer getting worse. You may be able to join if you are at least 18 years old, have a solid tumor that has spread, and are generally well enough to participate.","Participants will be followed for adverse events and serious adverse events for up to 3.5 years after treatment.",119,"Not specified in the trial record.","Not stated in the trial record.",[36,45],"v2"]