BMC Cancer. 2023;23(1):1056.

Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study.

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제1저자 오도연 · 교신저자 오도연

PMID 37919668 PMC10623721 DOI 10.1186/s12885-023-11539-1 IF 4.1 혈액종양내과

소속 (18)

Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Graduate School, Seoul, South Korea. ohdoyoun@snu.ac.kr.
Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
University of Pennsylvania, Philadelphia, PA, USA.
The Royal Marsden NHS Foundation Trust-Royal Marsden Hospital, London, UK.
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
Hospital Universitario, 12 de Octubre, Madrid, Spain.
Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Medical Oncology Department, Hospital Clinic i Provincial de Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
University of Kansas Hospital Cancer Center, Kansas City, KS, USA.
Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
The Christie NHS Foundation Trust, Manchester, UK.
Tufts Medical Center, Boston, MA, USA.
Orlando Health Cancer Institute, Orlando, FL, USA.
Henry Ford Hospital, Detroit, MI, USA.
Pharmacyclics LLC, an AbbVie Company, South San Francisco, CA, USA.
Sarah Cannon Research Institute - United Kingdom (SCRI-UK) and University College London, Cancer Institute, London, UK.

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.

Keywords

CetuximabColorectal carcinomaDocetaxelEverolimusGastric adenocarcinomaIbrutinibRenal cell carcinoma

Figures

**Fig. 1** PFS per investigator assessment in the a) RCC cohort, b) GC cohort, and c) CRC cohort. CI, confidence interval; CRC, colorectal carcinoma; GC, gastric adenocarcinoma; PFS, progression-free survival; RCC, renal cell carcinoma

**Fig. 2** OS in the a) RCC cohort, b) GC cohort, and c) CRC cohort. CI, confidence interval; CRC, colorectal carcinoma; GC, gastric adenocarcinoma; OS, overall survival; RCC, renal cell carcinoma

그림 출처: PubMed Central 공개 논문 (PMC10623721)

Conflict of interest statement

D-YO: consulting/advisory role with AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, Bristol Myers Squibb/Celgene, BeiGene, Basilea, and Turning Point Therapeutics; and research funding from AstraZeneca, Novartis, Array BioPharma, Eli Lilly, Servier, BeiGene, Merck Sharp & Dohme, and Handok; MAM: consulting/advisory role with Merck Sharp & Dohme, Bristol Myers Squibb, Eli Lilly, and Servier; and travel accommodations from Eli Lilly; DIQ: honoraria from and consulting/advisory role with Astellas, Bristol Myers Squibb, Bayer, Pfizer, Merck, EMD Serono, Genentech/Roche, and Seagen; and employment with AbbVie; PJO: consulting/advisory role with Genentech and Array BioPharma; research funding from Pfizer, Genentech, Bristol Myers Squibb, AstraZeneca, GlaxoSmithKline, Five Prime Therapeutics, Forty Seven, Merck, Syndax, bbi-biotech GmbH, Novartis, Celgene, Incyte, Eli Lilly/ImClone, Array BioPharma, H3 Biomedicine, Taiho, Minneamrita, Pharmacyclics LLC, an AbbVie Company, and Mirati; and expert testimony for Bayer and Eli Lilly; IC: honoraria from Eli Lilly and Eisai; consulting/advisory role with Eli Lilly, Bristol Myers Squibb, Merck Sharp & Dohme, Bayer, Roche, Merck-Serono, Five Prime Therapeutics, AstraZeneca, OncXerna, Pierre Fabre, Boehringer Ingelheim, Incyte, and Astellas; and institutional research funding from Eli Lilly, Sanofi Oncology, and Cilag-Janssen; SYK: institutional research funding from F. Hoffman-La Roche; ID: honoraria from Roche-Genentech, Merck Sharp & Dohme, Bristol Myers Squibb, Ipsen, AstraZeneca, and Eusa Pharma; consulting/advisory role with Roche-Genentech, Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, Ipsen, AstraZeneca, Debiopharm, Seagen, and Pharmacyclics, LLC, an AbbVie Company; institutional research funding from Roche and AstraZeneca; and travel accommodations from Ipsen and AstraZeneca; DC: honoraria from and consulting/advisory role with Astellas, Janssen, Roche, Merck, Ipsen, Exelixis, Pfizer, Bristol Myers Squibb, Eisai, and AstraZeneca; JB: consulting/advisory role with Ipsen, Bayer, QED, Eisai, Seagen, Mirati, Clovis, Insmed, and EMD Serono; institutional research funding from AbbVie, Bristol Myers Squibb, Boston Biomedical, I-Mab, Dragonfly, Symphogen, Immunomedics, Eli Lilly, Bayer (Loxo), EMD Serono, Incyte, Karyopharm, Pfizer, Astellas, and Atreca; travel accommodations from EMD Serono and Seagen; and other relationship (data and safety monitoring board) with Novocure, Karyopharm, and Pancreatic Cancer Action Network; BM: research funding from Roche, Bayer, and Janssen; speakers bureau with Roche, Sanofi, Janssen, Astellas, Pfizer, Novartis, Bristol Myers Squibb, and Ipsen; and travel accommodations and expenses from Pfizer and Janssen; SKW: stock or other ownership in Horizon Therapeutics, Merus, and Iovance Biotherapeutics; and institutional research funding from Daiichi Sankyo, Bayer Health, Acceleron Pharma, Sotio, Rogosin Institute, Pharmacyclics LLC, an AbbVie Company, Merck Serono, EMD Serono, Sanofi, Novartis, Nektar, Seagen, Astellas Pharma, Aleon Pharma, Bristol Myers Squibb, and Regeneron; K-WL: honoraria from Bristol Myers Squibb, Eli Lilly, and Genexine; consulting/advisory role with ISU ABXIS, Bayer, Bristol Myers Squibb, and Daiichi Sankyo; and institutional research funding from Ono Pharmaceutical, Merck Sharp & Dohme, AstraZeneca/MedImmune, Merck KGaA, Pfizer, MacroGenics, Green Cross, ABL Bio, Y-Biologics, Daiichi Sankyo, Taiho Pharmaceutical, Five Prime Therapeutics, Oncologie, Pharmacyclics, LLC, an AbbVie Company, LSK. BioPharma, ALX Oncology, Zymeworks, BeiGene, and Genexine; FM: consulting/advisory role and speakers bureau with, and travel accommodations from Servier; PM: reports no conflict of interest; MWS: research funding from Pharmacyclics LLC, an AbbVie Company; DW: consulting/advisory role with Castle Biosciences; EC: employment with and stock ownership in Pharmacyclics LLC, an AbbVie Company; JHR: employment with AbbVie and stock ownership in AbbVie; immediate family member stock ownership in Celgene/Bristol Myers Squibb; JPD: employment with and stock ownership in Pharmacyclics LLC, an AbbVie Company; HTA: employment with HCA Healthcare UK/Sarah Cannon Research Institute; honoraria from BeiGene, Bicycle, LabGenius, CellCentric, iOnctura, Taiho, Servier, and Guardant; consulting/advisory role with iOnctura, Engitix, LabGenius, CellCentric, Daiichi Sankyo, Bicycle, and BeiGene; institutional research funding from Sarah Cannon Research Institute; and speakers bureau with Servier and Guardant.

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