Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer
On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance. We performed a safety lead-in followed by expansion in endometrial...
Uloženo v:
| Vydáno v: | Clinical cancer research Ročník 27; číslo 23; s. 6354 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.12.2021
|
| Témata: | |
| ISSN: | 1557-3265, 1557-3265 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance.
We performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days.
A total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (
= 6); therefore, DL1 was reexplored (
= 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics.
The combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit. |
|---|---|
| AbstractList | On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance.
We performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days.
A total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (
= 6); therefore, DL1 was reexplored (
= 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics.
The combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit. On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance.PURPOSEOn the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance.We performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days.PATIENTS AND METHODSWe performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days.A total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (n = 6); therefore, DL1 was reexplored (n = 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics.RESULTSA total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (n = 6); therefore, DL1 was reexplored (n = 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics.The combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit.CONCLUSIONSThe combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit. |
| Author | Chelariu-Raicu, Anca Soliman, Pamela T Kim, Tae-Beom Frumovitz, Michael Labrie, Marilyne Blucher, Aurora Marszalek, Joseph R Yuan, Ying Liu, Jinsong Meyer, Larissa A Sood, Anil K Ma, XiaoYan Lu, Karen H Lee, Sanghoon Fang, Yong Schmeler, Katheleen M Chen, Tsun Hsuan Kabil, Nashwa Jazaeri, Amir Vellano, Christopher P Feng, Ningping Sun, Charlotte C Coleman, Robert L Westin, Shannon N Creason, Allison Litton, Jennifer K Murthy, Rashmi Fellman, Bryan Mills, Gordon B |
| Author_xml | – sequence: 1 givenname: Shannon N orcidid: 0000-0002-1922-0156 surname: Westin fullname: Westin, Shannon N email: swestin@mdanderson.org organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. swestin@mdanderson.org – sequence: 2 givenname: Marilyne surname: Labrie fullname: Labrie, Marilyne organization: Knight Cancer Institute and Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon – sequence: 3 givenname: Jennifer K surname: Litton fullname: Litton, Jennifer K organization: Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 4 givenname: Aurora orcidid: 0000-0001-6460-010X surname: Blucher fullname: Blucher, Aurora organization: Knight Cancer Institute and Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon – sequence: 5 givenname: Yong surname: Fang fullname: Fang, Yong organization: Knight Cancer Institute and Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon – sequence: 6 givenname: Christopher P surname: Vellano fullname: Vellano, Christopher P organization: TRACTION, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 7 givenname: Joseph R surname: Marszalek fullname: Marszalek, Joseph R organization: TRACTION, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 8 givenname: Ningping orcidid: 0000-0003-1917-9648 surname: Feng fullname: Feng, Ningping organization: TRACTION, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 9 givenname: XiaoYan surname: Ma fullname: Ma, XiaoYan organization: TRACTION, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 10 givenname: Allison orcidid: 0000-0001-5724-1276 surname: Creason fullname: Creason, Allison organization: Knight Cancer Institute and Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon – sequence: 11 givenname: Bryan surname: Fellman fullname: Fellman, Bryan organization: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 12 givenname: Ying surname: Yuan fullname: Yuan, Ying organization: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 13 givenname: Sanghoon surname: Lee fullname: Lee, Sanghoon organization: Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 14 givenname: Tae-Beom surname: Kim fullname: Kim, Tae-Beom organization: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 15 givenname: Jinsong surname: Liu fullname: Liu, Jinsong organization: Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 16 givenname: Anca orcidid: 0000-0003-2944-9488 surname: Chelariu-Raicu fullname: Chelariu-Raicu, Anca organization: Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany – sequence: 17 givenname: Tsun Hsuan surname: Chen fullname: Chen, Tsun Hsuan organization: Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 18 givenname: Nashwa surname: Kabil fullname: Kabil, Nashwa organization: AstraZeneca, Gaithersburg, Maryland – sequence: 19 givenname: Pamela T surname: Soliman fullname: Soliman, Pamela T organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 20 givenname: Michael surname: Frumovitz fullname: Frumovitz, Michael organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 21 givenname: Katheleen M surname: Schmeler fullname: Schmeler, Katheleen M organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 22 givenname: Amir orcidid: 0000-0003-4335-4151 surname: Jazaeri fullname: Jazaeri, Amir organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 23 givenname: Karen H surname: Lu fullname: Lu, Karen H organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 24 givenname: Rashmi orcidid: 0000-0002-0103-4718 surname: Murthy fullname: Murthy, Rashmi organization: Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 25 givenname: Larissa A orcidid: 0000-0002-2687-7463 surname: Meyer fullname: Meyer, Larissa A organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 26 givenname: Charlotte C surname: Sun fullname: Sun, Charlotte C organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 27 givenname: Anil K surname: Sood fullname: Sood, Anil K organization: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 28 givenname: Robert L orcidid: 0000-0001-9343-8754 surname: Coleman fullname: Coleman, Robert L organization: US Oncology Research, The Woodlands, Texas – sequence: 29 givenname: Gordon B orcidid: 0000-0002-0144-9614 surname: Mills fullname: Mills, Gordon B organization: Knight Cancer Institute and Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34518313$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkMtOwzAQRS1UBKXwCSAvWTTgR-ykyxLKQ6ooqmBdTZIJGCVOsNNC_4cPxSogsZk7I505I80RGdjWIiGnnF1wrtJLzpI0YrEUF1m2jASPuFZ6jwy5UkkkhVaDf_0hOfL-jTEecxYfkEMZK55KLofk6_EVPNL7nF63IWefHVhvWkvBlvTJhaGGPsxQ02koW4-ethVd1NCBMzk1lmZtkxu7o-iH6V9pBp3ZBKvrf4AlFmvn0PZ0Zsu2wd4ZqMfBbroaowd8CbsbpFcOwffj3eXFJtghuMEW6I7JfgW1x5PfHJHnm9lTdhfNF7f32XQeFVLpPtJVOtExJpDGpU4rlvBE5xKYjoVQiZYVLwsxkWmFiss8Z1UZo4BS54kodVEVYkTOf7yda9_X6PtVY3yBdQ0W27VfBYtQYsImIqBnv-g6b7Bcdc404Larv8-Kb_l2f8A |
| CitedBy_id | crossref_primary_10_1016_j_bbcan_2022_188804 crossref_primary_10_3390_ijms23031701 crossref_primary_10_1002_jcp_31015 crossref_primary_10_1080_14737140_2024_2393251 crossref_primary_10_1016_j_gore_2022_100974 crossref_primary_10_1080_13543784_2022_2067527 crossref_primary_10_3390_cancers14246257 crossref_primary_10_1016_j_tranon_2024_101893 crossref_primary_10_1016_j_biopha_2023_115676 crossref_primary_10_1007_s00044_025_03375_8 crossref_primary_10_1158_1078_0432_CCR_22_2585 crossref_primary_10_1200_PO_24_00614 crossref_primary_10_1038_s41416_023_02326_7 crossref_primary_10_3390_ijms241511890 crossref_primary_10_1177_17588359241255174 crossref_primary_10_3390_cancers14040897 crossref_primary_10_3390_cancers14174332 crossref_primary_10_3389_fonc_2023_1217805 crossref_primary_10_3389_fonc_2025_1547083 crossref_primary_10_3390_cancers15082357 crossref_primary_10_1080_14789450_2024_2432477 crossref_primary_10_3390_pharmaceutics15092241 crossref_primary_10_1016_j_currproblcancer_2024_101114 crossref_primary_10_1080_14789450_2022_2070065 crossref_primary_10_1038_s41698_024_00634_6 crossref_primary_10_1080_14712598_2024_2408756 crossref_primary_10_3390_biom13101480 crossref_primary_10_1038_s41392_024_01760_0 crossref_primary_10_1016_j_breast_2022_03_018 crossref_primary_10_1158_0008_5472_CAN_24_1846 crossref_primary_10_3389_fimmu_2022_1034903 crossref_primary_10_1186_s13046_024_03207_4 crossref_primary_10_3390_cimb47090702 crossref_primary_10_3390_ijms24032289 crossref_primary_10_1177_17588359231173183 crossref_primary_10_3390_biom14050585 crossref_primary_10_1136_ijgc_2022_003698 crossref_primary_10_3390_diagnostics15151872 crossref_primary_10_1007_s40265_024_01998_6 crossref_primary_10_1038_s41467_024_48637_y crossref_primary_10_3390_pharmaceutics17050554 |
| ContentType | Journal Article |
| Copyright | 2021 American Association for Cancer Research. |
| Copyright_xml | – notice: 2021 American Association for Cancer Research. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1158/1078-0432.CCR-21-1656 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1557-3265 |
| ExternalDocumentID | 34518313 |
| Genre | Journal Article Clinical Trial, Phase I Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: P50 CA098258 – fundername: NCI NIH HHS grantid: P50 CA217685 – fundername: NCI NIH HHS grantid: P30 CA016672 – fundername: NCI NIH HHS grantid: K07 CA201013 |
| GroupedDBID | --- 18M 29B 2FS 2WC 34G 39C 53G 5GY 5RE 5VS 6J9 AAFWJ AAJMC ABOCM ACGFO ACIWK ACPRK ADBBV ADCOW ADNWM AENEX AFHIN AFOSN AFRAH AFUMD ALMA_UNASSIGNED_HOLDINGS BAWUL BR6 BTFSW CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF EJD F5P FRP GX1 IH2 KQ8 L7B LSO NPM OK1 P0W P2P QTD RCR RHI RNS SJN TR2 W2D W8F WOQ YKV 7X8 |
| ID | FETCH-LOGICAL-c356t-6f8964e7a84d68f07176b3a064225763f1dc2938fe513bb0fd4e2ad6b72d6cfc2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 50 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000726530400001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1557-3265 |
| IngestDate | Thu Sep 04 20:21:55 EDT 2025 Mon Jul 21 05:59:06 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 23 |
| Language | English |
| License | 2021 American Association for Cancer Research. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c356t-6f8964e7a84d68f07176b3a064225763f1dc2938fe513bb0fd4e2ad6b72d6cfc2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0001-5724-1276 0000-0003-2944-9488 0000-0003-4335-4151 0000-0002-0144-9614 0000-0001-9343-8754 0000-0003-1917-9648 0000-0002-1922-0156 0000-0002-2687-7463 0000-0001-6460-010X 0000-0002-0103-4718 |
| OpenAccessLink | https://aacrjournals.org/clincancerres/article-pdf/27/23/6354/3015482/6354.pdf |
| PMID | 34518313 |
| PQID | 2572529092 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2572529092 pubmed_primary_34518313 |
| PublicationCentury | 2000 |
| PublicationDate | 2021-12-01 20211201 |
| PublicationDateYYYYMMDD | 2021-12-01 |
| PublicationDate_xml | – month: 12 year: 2021 text: 2021-12-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Clinical cancer research |
| PublicationTitleAlternate | Clin Cancer Res |
| PublicationYear | 2021 |
| SSID | ssj0014104 |
| Score | 2.5621705 |
| Snippet | On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 6354 |
| SubjectTerms | Antineoplastic Combined Chemotherapy Protocols - adverse effects Female Humans Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Phthalazines Piperazines Pyrimidines Pyrroles Triple Negative Breast Neoplasms - drug therapy |
| Title | Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/34518313 https://www.proquest.com/docview/2572529092 |
| Volume | 27 |
| WOSCitedRecordID | wos000726530400001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LT-MwELZYQKu98Fgey1NG2iOGxLFd54SgFLHSUioEqLfK8QMqsUmXloofxA9lxgnihITEJbnYThSP5_HNZD5CfqdJSIXNc-a0T5hQImGFNZ5pOFhWpsq52Ej79m-r29X9ft5rALdxU1b5phOjonaVRYz8EESLS54nOT8a_WfIGoXZ1YZC4xuZy8CVQalu9d-zCCKN9IFgMuEgcSWbP3hSqUFZYGdZkfGDdvuKcSRLlupjLzNam7PFr77nEllo_Ex6XAvGMpnx5U_y_aLJpK-Ql9492C_6p6CnFdw7z6AVEDijpnQ0GrCHBiakdd8SP6ZVoJcPBmkLCzosKagSCKvjKIpwLm2b0XBqML1fD7hCLB-7P9FO6ap_PjKE7MPqCO6zrr-LTcfpCdbFT_bjky-nsLqBtVEYH1fJzVnnun3OGsYGZjOpJkwFnSvhW0YLp3TAWFEVmcEgBwObLKTOgn-hg5dpVhRJcMJz41TR4k7ZYPkamS2r0v8iVHqrcpc4Cw6TgGnaRu6sJA4scr5B9t6-_wBOBKY5TOmrp_HgfQc2yHq9iYNR3bpjkAkJOizNNj8xe4v84FjAEmtXtslcAH3gd8i8nU6G48fdKGpw7fYuXgEJAN61 |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Phase+Ib+Dose+Expansion+and+Translational+Analyses+of+Olaparib+in+Combination+with+Capivasertib+in+Recurrent+Endometrial%2C+Triple-Negative+Breast%2C+and+Ovarian+Cancer&rft.jtitle=Clinical+cancer+research&rft.au=Westin%2C+Shannon+N&rft.au=Labrie%2C+Marilyne&rft.au=Litton%2C+Jennifer+K&rft.au=Blucher%2C+Aurora&rft.date=2021-12-01&rft.issn=1557-3265&rft.eissn=1557-3265&rft.volume=27&rft.issue=23&rft.spage=6354&rft_id=info:doi/10.1158%2F1078-0432.CCR-21-1656&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1557-3265&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1557-3265&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1557-3265&client=summon |