Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study
Abstract Background Ibrutinib, a first-in-class inhibitor of Bruton’s tyrosine kinase, is approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. Based on encouraging preclinical data, safety and efficacy of ibrutinib combined with companion drugs for advance...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11539-1 |
| _version_ | 1827770493284909056 |
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| author | Do-Youn Oh Maria Alsina Maqueda David I. Quinn Peter J. O’Dwyer Ian Chau Sun Young Kim Ignacio Duran Daniel Castellano Jordan Berlin Begona Mellado Stephen K. Williamson Keun-Wook Lee Francisca Marti Paul Mathew Muhammad Wasif Saif Ding Wang Elizabeth Chong Jacqueline Hilger-Rolfe James P. Dean Hendrik-Tobias Arkenau |
| author_facet | Do-Youn Oh Maria Alsina Maqueda David I. Quinn Peter J. O’Dwyer Ian Chau Sun Young Kim Ignacio Duran Daniel Castellano Jordan Berlin Begona Mellado Stephen K. Williamson Keun-Wook Lee Francisca Marti Paul Mathew Muhammad Wasif Saif Ding Wang Elizabeth Chong Jacqueline Hilger-Rolfe James P. Dean Hendrik-Tobias Arkenau |
| author_sort | Do-Youn Oh |
| collection | DOAJ |
| description | Abstract Background Ibrutinib, a first-in-class inhibitor of Bruton’s tyrosine kinase, is approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. Based on encouraging preclinical data, safety and efficacy of ibrutinib combined with companion drugs for advanced renal cell carcinoma (RCC), gastric/gastroesophageal junctional adenocarcinoma (GC), and colorectal adenocarcinoma (CRC) were evaluated. Methods Ibrutinib 560 mg or 840 mg once daily was administered with standard doses of everolimus for RCC, docetaxel for GC, and cetuximab for CRC. Endpoints included determination of the recommended phase 2 dose (RP2D) of ibrutinib in phase 1b and efficacy (overall response rate [ORR] for GC and CRC; progression-free survival [PFS] for CRC) in phase 2. Results A total of 39 (RCC), 46 (GC), and 50 (RCC) patients were enrolled and received the RP2D. Safety profiles were consistent with the individual agents used in the study. Confirmed ORRs were 3% (RCC), 21% (GC), and 19% (CRC). Median (90% CI) PFS was 5.6 (3.9–7.5) months in RCC, 4.0 (2.7–4.2) months in GC, and 5.4 (4.1–5.8) months in CRC. Conclusions Clinically meaningful increases in efficacy were not observed compared to historical controls; however, the data may warrant further evaluation of ibrutinib combinations in other solid tumours. Trial registration ClinicalTrials.gov, NCT02599324. |
| first_indexed | 2024-03-11T12:40:18Z |
| format | Article |
| id | doaj.art-1fe44534f0e94c6a89809b887b29866b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-11T12:40:18Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-1fe44534f0e94c6a89809b887b29866b2023-11-05T12:21:03ZengBMCBMC Cancer1471-24072023-11-0123111410.1186/s12885-023-11539-1Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 studyDo-Youn Oh0Maria Alsina Maqueda1David I. Quinn2Peter J. O’Dwyer3Ian Chau4Sun Young Kim5Ignacio Duran6Daniel Castellano7Jordan Berlin8Begona Mellado9Stephen K. Williamson10Keun-Wook Lee11Francisca Marti12Paul Mathew13Muhammad Wasif Saif14Ding Wang15Elizabeth Chong16Jacqueline Hilger-Rolfe17James P. Dean18Hendrik-Tobias Arkenau19Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Graduate SchoolVall d’Hebron Institute of Oncology (VHIO)University of Southern California Norris Comprehensive Cancer CenterUniversity of PennsylvaniaThe Royal Marsden NHS Foundation Trust-Royal Marsden HospitalAsan Medical Center, University of Ulsan College of MedicineHospital Universitario Marques de Valdecilla, IDIVALHospital UniversitarioVanderbilt-Ingram Cancer CenterMedical Oncology Department, Hospital Clinic i Provincial de Barcelona, IDIBAPS, University of BarcelonaUniversity of Kansas Hospital Cancer CenterSeoul National University College of Medicine, Seoul National University Bundang HospitalThe Christie NHS Foundation TrustTufts Medical CenterTufts Medical CenterHenry Ford HospitalPharmacyclics LLC, an AbbVie CompanyPharmacyclics LLC, an AbbVie CompanyPharmacyclics LLC, an AbbVie CompanySarah Cannon Research Institute – United Kingdom (SCRI-UK) and University College London, Cancer InstituteAbstract Background Ibrutinib, a first-in-class inhibitor of Bruton’s tyrosine kinase, is approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. Based on encouraging preclinical data, safety and efficacy of ibrutinib combined with companion drugs for advanced renal cell carcinoma (RCC), gastric/gastroesophageal junctional adenocarcinoma (GC), and colorectal adenocarcinoma (CRC) were evaluated. Methods Ibrutinib 560 mg or 840 mg once daily was administered with standard doses of everolimus for RCC, docetaxel for GC, and cetuximab for CRC. Endpoints included determination of the recommended phase 2 dose (RP2D) of ibrutinib in phase 1b and efficacy (overall response rate [ORR] for GC and CRC; progression-free survival [PFS] for CRC) in phase 2. Results A total of 39 (RCC), 46 (GC), and 50 (RCC) patients were enrolled and received the RP2D. Safety profiles were consistent with the individual agents used in the study. Confirmed ORRs were 3% (RCC), 21% (GC), and 19% (CRC). Median (90% CI) PFS was 5.6 (3.9–7.5) months in RCC, 4.0 (2.7–4.2) months in GC, and 5.4 (4.1–5.8) months in CRC. Conclusions Clinically meaningful increases in efficacy were not observed compared to historical controls; however, the data may warrant further evaluation of ibrutinib combinations in other solid tumours. Trial registration ClinicalTrials.gov, NCT02599324.https://doi.org/10.1186/s12885-023-11539-1Renal cell carcinomaGastric adenocarcinomaColorectal carcinomaIbrutinibEverolimusDocetaxel |
| spellingShingle | Do-Youn Oh Maria Alsina Maqueda David I. Quinn Peter J. O’Dwyer Ian Chau Sun Young Kim Ignacio Duran Daniel Castellano Jordan Berlin Begona Mellado Stephen K. Williamson Keun-Wook Lee Francisca Marti Paul Mathew Muhammad Wasif Saif Ding Wang Elizabeth Chong Jacqueline Hilger-Rolfe James P. Dean Hendrik-Tobias Arkenau Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study BMC Cancer Renal cell carcinoma Gastric adenocarcinoma Colorectal carcinoma Ibrutinib Everolimus Docetaxel |
| title | Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study |
| title_full | Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study |
| title_fullStr | Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study |
| title_full_unstemmed | Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study |
| title_short | Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study |
| title_sort | ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours results from a phase 1b 2 study |
| topic | Renal cell carcinoma Gastric adenocarcinoma Colorectal carcinoma Ibrutinib Everolimus Docetaxel |
| url | https://doi.org/10.1186/s12885-023-11539-1 |
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