Phase Ib/II study of ibrutinib (ibr) in combination with cetuximab (cetux) in patients (pts) with previously treated metastatic colorectal cancer (mCRC)
Oh DY, Arkenau T, Lee KW, Alsina M, Marti FM, Chung IJ, Saif W, Wang D, O'Dwyer P, Chau I, Lee MA, Chong E, Hilger-Rolfe J, Cole G, and Kim SY. Phase Ib/II study of ibrutinib (ibr) in combination with cetuximab (cetux) in patients (pts) with previously treated metastatic colorectal cancer (mCRC). Annals of Oncology 2020; 31:S428.
Annals of Oncology
Background: Third- or later-line treatments for mCRC have low response rates (1–37%) and limited PFS (1.4–5.6 mo) and OS (6.1–14.0 mo) (Arnold Ann Oncol 2018). Ibr is a once-daily Bruton’s tyrosine kinase (BTK) inhibitor approved for the treatment of various B-cell malignancies. Ibr also inhibits other kinases, including ETK, ITK, and EGFR tyrosine kinase (Wang Clin Cancer Res 2018; Dubovsky Blood 2013; Gao J Natl Cancer Inst 2014), and may provide complementary activity with cetux. Dual targeting of EGFR may improve OS in mCRC (Weickhardt J Clin Oncol 2012). This cohort of the phase Ib/II study (NCT02599324) evaluated efficacy and safety of ibr + cetux in pts with mCRC. Methods: Eligible pts had KRAS or NRAS wild type mCRC previously treated with 2–4 regimens and were cetux-naive. Pts received oral ibr once daily at 560 mg (starting dose) or 840 mg (recommended phase II dose) plus IV cetux (400 mg/m2 initial dose then 250 mg/m2 weekly) in 21-d cycles until unacceptable toxicity or progression. Efficacy (overall response rate [ORR], PFS, duration of response [DOR], disease control rate [DCR], and OS) and safety are reported. Results: 58 pts received ibr + cetux (ibr 560 mg, n=8; ibr 840 mg, n=50). Median age was 62 y; 38%, 40%, and 22% of pts had received 2, 3, and 4 prior regimens for mCRC, respectively. Median follow-up was 20.9 mo. ORR was 16% (Table). Median PFS was 4.8 mo (range 3.9–5.6). Median treatment duration was 3.2 mo for ibr and 3.0 mo for cetux. Grade ≥3 adverse events (AEs) occurred in 41 pts (71%); the only grade ≥3 AE occurring in ≥10% of pts was dermatitis acneiform (15 pts [26%]). Two pts (3%) had AEs leading to death; neither were related to study drug. Two pts (3%) had major hemorrhage and 53 pts (91%) had rash of any grade (grade ≥3 in 17 pts [29%]). Conclusions: Ibr + cetux was moderately active in heavily pretreated, refractory, cetux-naive pts with mCRC. There were no new safety signals and the safety profile was consistent with those of the individual drugs. [Formula presented] Clinical trial identification: NCT02599324.