474PPharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy
Abstract Background In this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), an anti-CTLA-4 antibody, in combination with one of four standard platinum-doublet chemotherapy regimens. We will present t...
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| Veröffentlicht in: | Annals of oncology 2019-10, Vol.30 (Supplement_5) |
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| creator | Hao, D Ellis, P M Laurie, S A Juergens, R A Mates, M Bradbury, P A Tsao, M Tehfe, M Kollmannsberger, C K Goffin, J R Wheatley-Price, P Hilton, J Robinson, A G Brown-Walker, P Tu, D Smoragiewicz, M Seymour, L K |
| description | Abstract
Background
In this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), an anti-CTLA-4 antibody, in combination with one of four standard platinum-doublet chemotherapy regimens. We will present the PK, and update overall survival data.
Methods
Regardless of tumour PD-L1 status, patients were enrolled into one of four cohorts: pemetrexed, gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin), each of which were evaluated in one of six dose levels [Table]. Dose escalation followed a Rolling Six type design. Concurrent enrollment of cohorts was allowed. Limited PK was collected ≤1 hour pre-dose and ≤10 minutes post-dose on day 1 of cycles 1-3 as well as week 6 or 8 post chemotherapy.
Results
One hundred and thirty-six patients (median age=62 (range 30-83); males:females=67:69; ECOG PS 0/1=32%/68%). The majority of patients had non-small cell (53.7%) or small cell (13.2%) lung cancer. Immune-related adverse events (irAEs) that were considered related to D or T were mainly |
| doi_str_mv | 10.1093/annonc/mdz244.036 |
| format | Article |
| fullrecord | <record><control><sourceid>oup</sourceid><recordid>TN_cdi_oup_primary_10_1093_annonc_mdz244_036</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/annonc/mdz244.036</oup_id><sourcerecordid>10.1093/annonc/mdz244.036</sourcerecordid><originalsourceid>FETCH-oup_primary_10_1093_annonc_mdz244_0363</originalsourceid><addsrcrecordid>eNqVkMtKxDAYhYMoWC8P4O5fKtiZ9DIdux4VRZAu3Je_SWqjuZQ0Galv5cYH8MmMji_g6vDB4Rz4CDnL6CKjdbFEY6xhS83f87Jc0KLaI0m2qur0ipbZPklonRfpelWUh-Roml4opVWd1wn5LNdl0wzoNDL7Ko3wksF583ABaDiEkaMXHKbgtnKLCiIi9M5q8IOADRrkEg0wNEw48E6imuDZ2TDC_eP1Is8rmHzgM9geeBxBFTR28PURu0ILJfUvyzhhdScNemkNvEk_wKgimKBTbkOnhAc2CG3jrcNxPiEHfbwSp395TC5vb542d2l8bkcnNbq5zWj746bduWl3btropvhn_RtsEnMH</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>474PPharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Hao, D ; Ellis, P M ; Laurie, S A ; Juergens, R A ; Mates, M ; Bradbury, P A ; Tsao, M ; Tehfe, M ; Kollmannsberger, C K ; Goffin, J R ; Wheatley-Price, P ; Hilton, J ; Robinson, A G ; Brown-Walker, P ; Tu, D ; Smoragiewicz, M ; Seymour, L K</creator><creatorcontrib>Hao, D ; Ellis, P M ; Laurie, S A ; Juergens, R A ; Mates, M ; Bradbury, P A ; Tsao, M ; Tehfe, M ; Kollmannsberger, C K ; Goffin, J R ; Wheatley-Price, P ; Hilton, J ; Robinson, A G ; Brown-Walker, P ; Tu, D ; Smoragiewicz, M ; Seymour, L K</creatorcontrib><description>Abstract
Background
In this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), an anti-CTLA-4 antibody, in combination with one of four standard platinum-doublet chemotherapy regimens. We will present the PK, and update overall survival data.
Methods
Regardless of tumour PD-L1 status, patients were enrolled into one of four cohorts: pemetrexed, gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin), each of which were evaluated in one of six dose levels [Table]. Dose escalation followed a Rolling Six type design. Concurrent enrollment of cohorts was allowed. Limited PK was collected ≤1 hour pre-dose and ≤10 minutes post-dose on day 1 of cycles 1-3 as well as week 6 or 8 post chemotherapy.
Results
One hundred and thirty-six patients (median age=62 (range 30-83); males:females=67:69; ECOG PS 0/1=32%/68%). The majority of patients had non-small cell (53.7%) or small cell (13.2%) lung cancer. Immune-related adverse events (irAEs) that were considered related to D or T were mainly </=Grade 2, the most common of which were skin (38%), diarrhea/colitis (29%), and hypothyroidism (18%). Cmax and Ctrough increased in a dose-proportional manner over the dose range of 1 to 3 mg/kg for tremelimumab Q3W. PK exposures for both durvalumab at 15 mg/kg, 1125mg, or 1500mg Q3W and tremelimumab at 1, 3 mg/kg, 56, and 75mg demonstrated accumulation after the administration of multiple doses. PK parameters did not appear to differ across platinum-doublets. After a median follow-up of 19.6 months, 19 patients continued on protocol therapy. Survival data will be updated prior to the meeting. Table
Table:474PDose LevelDurvalumab Q3WTremelimumab (with chemotherapy)Tremelimumab (after chemotherapy)015mg/kg--115mg/kg1 mg/kg X 11-2 doses2a15mg/kg1 mg/kg X 3 Q6w1-2 doses2b15mg/kg3 mg/kg X 11-2 doses Q6w31125mg56 mg X 4 Q3w56 mg X 2 Q3w41500mg75 mg X 4 Q3w75 mg X 1
Conclusions
Standard platinum-doublet chemotherapy regimens did not alter the PK of D+T or D compared with historical monotherapy therapy data. Toxicities were manageable and were not associated with PK.
Clinical trial identification
NCT02537418.
Legal entity responsible for the study
Canadian Cancer Trials Group (CCTG).
Funding
AstraZeneca provided drug and partial funding to support of this Canadian Cancer Trials Group (CCTG) study.
Disclosure
D. Hao: Honoraria (self), Advisory Board: Roche; Honoraria (self), Advisory Board; funding for clinical trial: BMS; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: Merck; Honoraria (self), Advisory Board: BI. P.M. Ellis: Honoraria (self), Advisory / Consultancy, Advisory Board: AstraZeneca; Advisory / Consultancy, Advisory Board: Takeda; Honoraria (self), Advisory / Consultancy, Advisory Board: Abbvie; Honoraria (self): Pfizer; Honoraria (self): BMS. R.A. Juergens: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer. P.A. Bradbury: Honoraria (self), Advisory / Consultancy: Abbvie; Honoraria (self): Pfizer; Honoraria (self): Lilly; Advisory / Consultancy: BI. M. Tsao: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck. M. Tehfe: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celegen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda. C.K. Kollmannsberger: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Sanofi. J.R. Goffin: Honoraria (self), Speaker Bureau / Expert testimony, 2014, 2018: Amgen; Honoraria (self), 2015: Boehringer Ingelheim; Honoraria (self), 2015: Bristol-Myers Squibb; Honoraria (self), 2018: Merck; Travel / Accommodation / Expenses, 2017: AstraZeneca. P. Wheatley-Price: Advisory / Consultancy: Takeda; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Abbvie; Advisory / Consultancy: Roche. J. Hilton: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Puma; Advisory / Consultancy: Eli Lilly. L.K. Seymour: Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Received funding on behalf of CCTG from AstraZeneca to support the study: AstraZeneca. All other authors have declared no conflicts of interest.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdz244.036</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>Annals of oncology, 2019-10, Vol.30 (Supplement_5)</ispartof><rights>European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids></links><search><creatorcontrib>Hao, D</creatorcontrib><creatorcontrib>Ellis, P M</creatorcontrib><creatorcontrib>Laurie, S A</creatorcontrib><creatorcontrib>Juergens, R A</creatorcontrib><creatorcontrib>Mates, M</creatorcontrib><creatorcontrib>Bradbury, P A</creatorcontrib><creatorcontrib>Tsao, M</creatorcontrib><creatorcontrib>Tehfe, M</creatorcontrib><creatorcontrib>Kollmannsberger, C K</creatorcontrib><creatorcontrib>Goffin, J R</creatorcontrib><creatorcontrib>Wheatley-Price, P</creatorcontrib><creatorcontrib>Hilton, J</creatorcontrib><creatorcontrib>Robinson, A G</creatorcontrib><creatorcontrib>Brown-Walker, P</creatorcontrib><creatorcontrib>Tu, D</creatorcontrib><creatorcontrib>Smoragiewicz, M</creatorcontrib><creatorcontrib>Seymour, L K</creatorcontrib><title>474PPharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy</title><title>Annals of oncology</title><description>Abstract
Background
In this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), an anti-CTLA-4 antibody, in combination with one of four standard platinum-doublet chemotherapy regimens. We will present the PK, and update overall survival data.
Methods
Regardless of tumour PD-L1 status, patients were enrolled into one of four cohorts: pemetrexed, gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin), each of which were evaluated in one of six dose levels [Table]. Dose escalation followed a Rolling Six type design. Concurrent enrollment of cohorts was allowed. Limited PK was collected ≤1 hour pre-dose and ≤10 minutes post-dose on day 1 of cycles 1-3 as well as week 6 or 8 post chemotherapy.
Results
One hundred and thirty-six patients (median age=62 (range 30-83); males:females=67:69; ECOG PS 0/1=32%/68%). The majority of patients had non-small cell (53.7%) or small cell (13.2%) lung cancer. Immune-related adverse events (irAEs) that were considered related to D or T were mainly </=Grade 2, the most common of which were skin (38%), diarrhea/colitis (29%), and hypothyroidism (18%). Cmax and Ctrough increased in a dose-proportional manner over the dose range of 1 to 3 mg/kg for tremelimumab Q3W. PK exposures for both durvalumab at 15 mg/kg, 1125mg, or 1500mg Q3W and tremelimumab at 1, 3 mg/kg, 56, and 75mg demonstrated accumulation after the administration of multiple doses. PK parameters did not appear to differ across platinum-doublets. After a median follow-up of 19.6 months, 19 patients continued on protocol therapy. Survival data will be updated prior to the meeting. Table
Table:474PDose LevelDurvalumab Q3WTremelimumab (with chemotherapy)Tremelimumab (after chemotherapy)015mg/kg--115mg/kg1 mg/kg X 11-2 doses2a15mg/kg1 mg/kg X 3 Q6w1-2 doses2b15mg/kg3 mg/kg X 11-2 doses Q6w31125mg56 mg X 4 Q3w56 mg X 2 Q3w41500mg75 mg X 4 Q3w75 mg X 1
Conclusions
Standard platinum-doublet chemotherapy regimens did not alter the PK of D+T or D compared with historical monotherapy therapy data. Toxicities were manageable and were not associated with PK.
Clinical trial identification
NCT02537418.
Legal entity responsible for the study
Canadian Cancer Trials Group (CCTG).
Funding
AstraZeneca provided drug and partial funding to support of this Canadian Cancer Trials Group (CCTG) study.
Disclosure
D. Hao: Honoraria (self), Advisory Board: Roche; Honoraria (self), Advisory Board; funding for clinical trial: BMS; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: Merck; Honoraria (self), Advisory Board: BI. P.M. Ellis: Honoraria (self), Advisory / Consultancy, Advisory Board: AstraZeneca; Advisory / Consultancy, Advisory Board: Takeda; Honoraria (self), Advisory / Consultancy, Advisory Board: Abbvie; Honoraria (self): Pfizer; Honoraria (self): BMS. R.A. Juergens: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer. P.A. Bradbury: Honoraria (self), Advisory / Consultancy: Abbvie; Honoraria (self): Pfizer; Honoraria (self): Lilly; Advisory / Consultancy: BI. M. Tsao: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck. M. Tehfe: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celegen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda. C.K. Kollmannsberger: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Sanofi. J.R. Goffin: Honoraria (self), Speaker Bureau / Expert testimony, 2014, 2018: Amgen; Honoraria (self), 2015: Boehringer Ingelheim; Honoraria (self), 2015: Bristol-Myers Squibb; Honoraria (self), 2018: Merck; Travel / Accommodation / Expenses, 2017: AstraZeneca. P. Wheatley-Price: Advisory / Consultancy: Takeda; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Abbvie; Advisory / Consultancy: Roche. J. Hilton: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Puma; Advisory / Consultancy: Eli Lilly. L.K. Seymour: Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Received funding on behalf of CCTG from AstraZeneca to support the study: AstraZeneca. All other authors have declared no conflicts of interest.</description><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqVkMtKxDAYhYMoWC8P4O5fKtiZ9DIdux4VRZAu3Je_SWqjuZQ0Galv5cYH8MmMji_g6vDB4Rz4CDnL6CKjdbFEY6xhS83f87Jc0KLaI0m2qur0ipbZPklonRfpelWUh-Roml4opVWd1wn5LNdl0wzoNDL7Ko3wksF583ABaDiEkaMXHKbgtnKLCiIi9M5q8IOADRrkEg0wNEw48E6imuDZ2TDC_eP1Is8rmHzgM9geeBxBFTR28PURu0ILJfUvyzhhdScNemkNvEk_wKgimKBTbkOnhAc2CG3jrcNxPiEHfbwSp395TC5vb542d2l8bkcnNbq5zWj746bduWl3btropvhn_RtsEnMH</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Hao, D</creator><creator>Ellis, P M</creator><creator>Laurie, S A</creator><creator>Juergens, R A</creator><creator>Mates, M</creator><creator>Bradbury, P A</creator><creator>Tsao, M</creator><creator>Tehfe, M</creator><creator>Kollmannsberger, C K</creator><creator>Goffin, J R</creator><creator>Wheatley-Price, P</creator><creator>Hilton, J</creator><creator>Robinson, A G</creator><creator>Brown-Walker, P</creator><creator>Tu, D</creator><creator>Smoragiewicz, M</creator><creator>Seymour, L K</creator><general>Oxford University Press</general><scope/></search><sort><creationdate>20191001</creationdate><title>474PPharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy</title><author>Hao, D ; Ellis, P M ; Laurie, S A ; Juergens, R A ; Mates, M ; Bradbury, P A ; Tsao, M ; Tehfe, M ; Kollmannsberger, C K ; Goffin, J R ; Wheatley-Price, P ; Hilton, J ; Robinson, A G ; Brown-Walker, P ; Tu, D ; Smoragiewicz, M ; Seymour, L K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-oup_primary_10_1093_annonc_mdz244_0363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hao, D</creatorcontrib><creatorcontrib>Ellis, P M</creatorcontrib><creatorcontrib>Laurie, S A</creatorcontrib><creatorcontrib>Juergens, R A</creatorcontrib><creatorcontrib>Mates, M</creatorcontrib><creatorcontrib>Bradbury, P A</creatorcontrib><creatorcontrib>Tsao, M</creatorcontrib><creatorcontrib>Tehfe, M</creatorcontrib><creatorcontrib>Kollmannsberger, C K</creatorcontrib><creatorcontrib>Goffin, J R</creatorcontrib><creatorcontrib>Wheatley-Price, P</creatorcontrib><creatorcontrib>Hilton, J</creatorcontrib><creatorcontrib>Robinson, A G</creatorcontrib><creatorcontrib>Brown-Walker, P</creatorcontrib><creatorcontrib>Tu, D</creatorcontrib><creatorcontrib>Smoragiewicz, M</creatorcontrib><creatorcontrib>Seymour, L K</creatorcontrib><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hao, D</au><au>Ellis, P M</au><au>Laurie, S A</au><au>Juergens, R A</au><au>Mates, M</au><au>Bradbury, P A</au><au>Tsao, M</au><au>Tehfe, M</au><au>Kollmannsberger, C K</au><au>Goffin, J R</au><au>Wheatley-Price, P</au><au>Hilton, J</au><au>Robinson, A G</au><au>Brown-Walker, P</au><au>Tu, D</au><au>Smoragiewicz, M</au><au>Seymour, L K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>474PPharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy</atitle><jtitle>Annals of oncology</jtitle><date>2019-10-01</date><risdate>2019</risdate><volume>30</volume><issue>Supplement_5</issue><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>Abstract
Background
In this phase Ib multicenter study, we sought to characterize the PK, safety and tolerability of durvalumab (D), an anti-PD-L1 antibody, ± tremelimumab (T), an anti-CTLA-4 antibody, in combination with one of four standard platinum-doublet chemotherapy regimens. We will present the PK, and update overall survival data.
Methods
Regardless of tumour PD-L1 status, patients were enrolled into one of four cohorts: pemetrexed, gemcitabine, etoposide (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin), each of which were evaluated in one of six dose levels [Table]. Dose escalation followed a Rolling Six type design. Concurrent enrollment of cohorts was allowed. Limited PK was collected ≤1 hour pre-dose and ≤10 minutes post-dose on day 1 of cycles 1-3 as well as week 6 or 8 post chemotherapy.
Results
One hundred and thirty-six patients (median age=62 (range 30-83); males:females=67:69; ECOG PS 0/1=32%/68%). The majority of patients had non-small cell (53.7%) or small cell (13.2%) lung cancer. Immune-related adverse events (irAEs) that were considered related to D or T were mainly </=Grade 2, the most common of which were skin (38%), diarrhea/colitis (29%), and hypothyroidism (18%). Cmax and Ctrough increased in a dose-proportional manner over the dose range of 1 to 3 mg/kg for tremelimumab Q3W. PK exposures for both durvalumab at 15 mg/kg, 1125mg, or 1500mg Q3W and tremelimumab at 1, 3 mg/kg, 56, and 75mg demonstrated accumulation after the administration of multiple doses. PK parameters did not appear to differ across platinum-doublets. After a median follow-up of 19.6 months, 19 patients continued on protocol therapy. Survival data will be updated prior to the meeting. Table
Table:474PDose LevelDurvalumab Q3WTremelimumab (with chemotherapy)Tremelimumab (after chemotherapy)015mg/kg--115mg/kg1 mg/kg X 11-2 doses2a15mg/kg1 mg/kg X 3 Q6w1-2 doses2b15mg/kg3 mg/kg X 11-2 doses Q6w31125mg56 mg X 4 Q3w56 mg X 2 Q3w41500mg75 mg X 4 Q3w75 mg X 1
Conclusions
Standard platinum-doublet chemotherapy regimens did not alter the PK of D+T or D compared with historical monotherapy therapy data. Toxicities were manageable and were not associated with PK.
Clinical trial identification
NCT02537418.
Legal entity responsible for the study
Canadian Cancer Trials Group (CCTG).
Funding
AstraZeneca provided drug and partial funding to support of this Canadian Cancer Trials Group (CCTG) study.
Disclosure
D. Hao: Honoraria (self), Advisory Board: Roche; Honoraria (self), Advisory Board; funding for clinical trial: BMS; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Advisory Board; funding for clinical trial: Merck; Honoraria (self), Advisory Board: BI. P.M. Ellis: Honoraria (self), Advisory / Consultancy, Advisory Board: AstraZeneca; Advisory / Consultancy, Advisory Board: Takeda; Honoraria (self), Advisory / Consultancy, Advisory Board: Abbvie; Honoraria (self): Pfizer; Honoraria (self): BMS. R.A. Juergens: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer. P.A. Bradbury: Honoraria (self), Advisory / Consultancy: Abbvie; Honoraria (self): Pfizer; Honoraria (self): Lilly; Advisory / Consultancy: BI. M. Tsao: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck. M. Tehfe: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Celegen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda. C.K. Kollmannsberger: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Sanofi. J.R. Goffin: Honoraria (self), Speaker Bureau / Expert testimony, 2014, 2018: Amgen; Honoraria (self), 2015: Boehringer Ingelheim; Honoraria (self), 2015: Bristol-Myers Squibb; Honoraria (self), 2018: Merck; Travel / Accommodation / Expenses, 2017: AstraZeneca. P. Wheatley-Price: Advisory / Consultancy: Takeda; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Abbvie; Advisory / Consultancy: Roche. J. Hilton: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Puma; Advisory / Consultancy: Eli Lilly. L.K. Seymour: Research grant / Funding (institution), Shareholder / Stockholder / Stock options, Received funding on behalf of CCTG from AstraZeneca to support the study: AstraZeneca. All other authors have declared no conflicts of interest.</abstract><pub>Oxford University Press</pub><doi>10.1093/annonc/mdz244.036</doi></addata></record> |
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| language | eng |
| recordid | cdi_oup_primary_10_1093_annonc_mdz244_036 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| title | 474PPharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T20%3A11%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-oup&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=474PPharmacokinetic%20(PK)%20and%20updated%20survival%20data%20from%20the%20Canadian%20cancer%20trials%20group%20IND.226%20study%20of%20durvalumab%20%C2%B1%20tremelimumab%20in%20combination%20with%20platinum-doublet%20chemotherapy&rft.jtitle=Annals%20of%20oncology&rft.au=Hao,%20D&rft.date=2019-10-01&rft.volume=30&rft.issue=Supplement_5&rft.issn=0923-7534&rft.eissn=1569-8041&rft_id=info:doi/10.1093/annonc/mdz244.036&rft_dat=%3Coup%3E10.1093/annonc/mdz244.036%3C/oup%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rft_oup_id=10.1093/annonc/mdz244.036&rfr_iscdi=true |