[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-380268-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-380268-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","a-signal-seeking-phase-2-study-of-olaparib-and-durvalumab-in-advanced-solid-cancers-with-homologous-recombination-repair-gene-alterations-overview-of-safety-and-efficacy","A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations - Overview of safety and efficacy","","A signal-seeking Phase II clinical trial evaluates PARP plus PD-L1 inhibition with olaparib and durvalumab in patients with advanced solid tumors carrying homologous recombination repair (HRR) defects, including predominantly rare cancers. Forty-eight patients received the combination, with cohorts defined by BRCA1/2 alterations versus other selected HRR alterations. The primary endpoint is progression-free survival at 6 months, with post hoc exploratory analyses using archival tumor tissue and serial blood samples. Results report a 35–38% PFS6 rate and durable objective tumor responses. The combination shows no new toxicity signals and identifies potential prognostic immune markers.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/a-signal-seeking-phase-2-study-of-olaparib-and-durvalumab-in-advanced-solid-cancers-with-homologous-recombination-repair-gene-alterations-overview-of-safety-and-efficacy/380268/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/a-signal-seeking-phase-2-study-of-olaparib-and-durvalumab-in-advanced-solid-cancers-with-homologous-recombination-repair-gene-alterations-overview-of-safety-and-efficacy/380268.png","ImageObject",300,407,{"name":42,"@type":43},"Jordan Avery","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What treatment combination is studied in this Phase 2 trial?","Question",{"text":63,"@type":64},"The study evaluates olaparib (PARP inhibition) plus durvalumab (PD-L1 inhibition) in advanced solid cancers with HRR gene alterations.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were patients grouped for analysis?",{"text":68,"@type":64},"Patients were treated with olaparib plus durvalumab and analyzed in two cohorts: those with BRCA1/2 alterations (group 1) and those with other selected HRR alterations (group 2).",{"name":70,"@type":61,"acceptedAnswer":71},"What were the main efficacy and safety outcomes?",{"text":72,"@type":64},"Progression-free survival at 6 months was reported as 35% (group 1) and 38% (group 2), alongside durable objective tumor responses. The combination was considered safe, with serious adverse events related to the study drugs occurring in 3 (6%) patients and no new toxicity concerns in the conclusions.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},380268,1790319946,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},1099523882367,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","British Journal of Cancer [www.nature.com/bjc](www.nature.com/bjc)  \nARTICLE OPEN   \nA signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations  \nSubotheni Thavaneswaran 1,2,3,4,13 ✉, Maya Kansara3,4,13, Frank Lin1,3,4,5, David Espinoza1, John P. Grady 3,4, Chee Khoon Lee1, Mandy L. Ballinger3,4, Lucille Sebastian 1, Theresa Corpuz3,4, Min Ru Qiu3,6, Piyushkumar Mundra3,4, Charles G. Bailey7,8,9, Ulf Schmitz 8,9,10,11, John Simes 1, Anthony M. Joshua 2,3,4 and David M. Thomas2,4,12  \n© The Author(s) 2023  \n\n|  | PURPOSE: To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects.\u003Cbr>PATIENTS AND METHODS: In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other select HRR alterations (group 2) . Overall, 32 (66%) patients had rare or less common cancers. The primary objective of this singlearm Phase II trial was a progression-free survival rate at 6 months (PFS6) . Post hoc exploratory analyses were conducted on archival tumour tissue and serial bloods.\u003Cbr>RESULTS: The PFS6 rate was 35% and 38% with durable objective tumour responses (OTR) in 3(19%) and 3(9%) in groups 1 and 2, respectively. Rare cancers achieving an OTR included cholangiocarcinoma, perivascular epithelioid cell (PEComa), neuroendocrine, gallbladder and endometrial cancer. O + D was safe, with five serious adverse events related to the study drug(s) in 3 (6%) patients. A higher proportion of CD38 high B cells in the blood and higher CD40 expression in tumour was prognostic of survival. CONCLUSIONS: O + D demonstrated no new toxicity concerns and yielded a clinically meaningful PFS6 rate and durable OTRs |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| across several cancers with HRR defects, including rare cancers. |  |  |\n|  | British Journal of Cancer (2023) 129:475–485; [https://doi.org/10.1038/s41416-023-02311-0](https://doi.org/10.1038/s41416-023-02311-0) |  |\n|  |  |  |\n\nBACKGROUND  \nHomologous recombination repair (HRR) is comprised of interwoven pathways that function in the repair of DNA doublestranded breaks and interstrand crosslinks [1] . An inability to repair complex DNA damage and resolve DNA replication strain results in genomic instability and promotes cancer development [1] . BRCA1 and 2 are the best-characterised HRR genes and predispose to breast and ovarian cancer [2, 3] . Several additional genes have been implicated in this repair pathway and many studies have characterised the exploitation of these inherent defects for therapeutic opportunities [4–6] .  \nThe use of poly-ADP ribose polymerase (PARP) inhibitors has synthetically lethal activity in the presence of non-functional HRR. Olaparib monotherapy has yielded a prolonged progression-free survival in patients with relapsed platinum-sensitive high-grade serous ovarian cancer, particularly in the presence of germline or somatic BRCA1/2 alteration [7–10] . Similarly, improved outcomes  \nhave been observed with olaparib across a range of cancer histotypes harbouring BRCA1/2, or other HRR gene alterations [5, 11–15] . Generally, patients with BRCA mutations derived greater benefits from olaparib treatment compared with other HRR gene alterations [16] .  \nThere is significant interest in the immunological consequences of DNA damage. Preclinical data suggest that DNA damage detected by the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway triggers a proinflammatory cascade of cytokines [17] . Preclinically, PARP inhibition elicits a potent antitumour immune response through activation of the STING pathway in both BRCA1-deficient tumour cells and dendritic cells, possibly indicating an association between innat","cbCaipajS8CKyU41","https://ap.wps.com/l/cbCaipajS8CKyU41","pdf",1308583,11,"English","# Purpose\n## Patients and methods\n# Results\n## Progression-free survival and objective tumor responses\n# Conclusions\n## Safety and prognostic markers","[{\"question\":\"What treatment combination is studied in this Phase 2 trial?\",\"answer\":\"The study evaluates olaparib (PARP inhibition) plus durvalumab (PD-L1 inhibition) in advanced solid cancers with HRR gene alterations.\"},{\"question\":\"How were patients grouped for analysis?\",\"answer\":\"Patients were treated with olaparib plus durvalumab and analyzed in two cohorts: those with BRCA1/2 alterations (group 1) and those with other selected HRR alterations (group 2).\"},{\"question\":\"What were the main efficacy and safety outcomes?\",\"answer\":\"Progression-free survival at 6 months was reported as 35% (group 1) and 38% (group 2), alongside durable objective tumor responses. The combination was considered safe, with serious adverse events related to the study drugs occurring in 3 (6%) patients and no new toxicity concerns in the conclusions.\"}]","A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations - Overview of safety and efficacy | PDF",1790239474,28]