439P - Phase Ib/II study of ibrutinib (ibr) in combination with cetuximab (cetux) in patients (pts) with previously treated metastatic colorectal cancer (mCRC)

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. Table: 439P

*Confirmed by repeat assessments ≥28 days apart.

Clinical trial identification

NCT02599324.

Editorial acknowledgement

Medical writing support was provided by Melanie Sweetlove, MSc, and was funded by Pharmacyclics LLC.

Legal entity responsible for the study

Pharmacyclics LLC, an AbbVie Company.

Funding

Pharmacyclics LLC, an AbbVie Company.

Disclosure

D-Y. Oh: Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: Mereck Serono; Advisory/Consultancy: Bayer; Advisory/Consultancy: Taiho; Advisory/Consultancy: ASLAN; Advisory/Consultancy: Halozyme; Advisory/Consultancy: Zymeworks; Research grant/Funding (self): Array; Research grant/Funding (self): Eli Lilly. T. Arkenau: Research grant/Funding (self), Full/Part-time employment: HCA/Sarah Cannon; Honoraria (self): Roche; Honoraria (self): Guardant; Honoraria (self): Bayer; Honoraria (self): Bicycle; Honoraria (self): Servier. K-W. Lee: Honoraria (self): BMS; Honoraria (self): Eli Lilly; Honoraria (self): Genexine; Research grant/Funding (self): Ono pharmaceutical; Research grant/Funding (self): Merck Sharp & Dohme Corp., AstraZeneca/MedImmune, Merck KGaA; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Macrogenics; Research grant/Funding (self): Green Cross Corp; Research grant/Funding (self): Five Prime Therapeutics; Research grant/Funding (self): Pharmacyclics LLC, an Abbvie Company; Research grant/Funding (self): LSK BioPharm. M. Alsina: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Amgen. F.M. Marti: Honoraria (self), Travel/Accommodation/Expenses: SERVIER PHARMACEUTICALS. W. Saif: Research grant/Funding (self): Pharmacyclics LLC, an Abbvie Company. D. Wang: Advisory/Consultancy, Travel/Accommodation/Expenses: Qurgen, Inc. P. O'Dwyer: Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): Celgene; Advisory/Consultancy, Research grant/Funding (self): Array; Research grant/Funding (self): Pfizer; Research grant/Funding (self): BMS; Research grant/Funding (self): GSK; Research grant/Funding (self): Five Prime; Research grant/Funding (self): FortySeven; Research grant/Funding (self): BBI; Research grant/Funding (self): Novartis; Research grant/Funding (self): Incyte; Research grant/Funding (self): Lilly/Imclone; Research grant/Funding (self): h3biomedicine; Research grant/Funding (self): Taiho; Research grant/Funding (self): Pharmacyclics LLC, an Abbvie Company; Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: Lilly. I. Chau: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck-Serono; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Astra-Zeneca; Advisory/Consultancy: Oncologie International; Advisory/Consultancy: Pierre-Fabre; Research grant/Funding (self): Janssen-Cilag; Research grant/Funding (self): Sanofi Oncology. E. Chong: Full/Part-time employment: Pharmacyclics LLC, an Abbvie Company. J. Hilger-Rolfe: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pharmacyclics LLC, an Abbvie Company; Shareholder/Stockholder/Stock options: Abbvie; Shareholder/Stockholder/Stock options: Celgene; Shareholder/Stockholder/Stock options: BMS. G. Cole Jr: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. S.Y. Kim: Research grant/Funding (self): Roche. All other authors have declared no conflicts of interest.