Abstract 620P
Background
Angiogenesis is a crucial mechanism in colorectal cancer (CRC) development and progression, and anti-angiogenic drugs are a mainstay of CRC systemic treatment.
Methods
We conducted, according to Simon’s “minimax” two stage design, an open-label, single arm phase II trial to evaluate the antitumor activity of cabozantinib in pretreated metastatic CRC (mCRC) patients (pts), that progressed after at least 2 lines of prior therapy for metastatic disease. The primary endpoint was the Progression Free Survival (PFS) rate at 16 weeks; secondary endpoints include PFS, Overall Survival (OS), Response Rate (RR), Disease Control Rate, safety. Here we present the initial exploratory biomarkers analysis.
Results
From October 2019 to January 2023 a total of 33 (19 male and 14 female) pts, median age of 58 years (30-79), were treated with cabozantinib 60 mg/daily per os. A comprehensive genomic profiling by next generation sequencing (NGS) was performed with FoundationOne CDx and FoundationOne Liquid CDx (324 genes) on tumor tissue (20/33) and plasma circulating tumor DNA (ctDNA) (15/33) both in 8/33 pts. 11 out of 33 patients were free of progression at 16 weeks and were considered responders and among these the NGS analysis was available at the time of abstract submission in 10 pts. No specific genetic feature was identified in responders, only 1 patient had AXL amplification (that represents a potential target of cabozantinib). Of note MET amplification found in 2/25 pts did not correlate with response to cabozantinib. In not responding pts SMAD4 mutation as well as genetic alteration defying a “BRCAness" phenotype were most reported. RNASeq analysis is currently ongoing in 26/33 (78.8%) patient samples.
Conclusions
The ABACO study showed clinical activity of cabozantinib in a subset of refractory mCRC, to the date of the analysis no predictive markers were identified so far. Further analysis are ongoing.
Clinical trial identification
EudraCT 2019-000674-28.
Editorial acknowledgement
Legal entity responsible for the study
Department of Precision Medicine.
Funding
Ipsen partially funded.
Disclosure
F. Ciardiello: Financial Interests, Personal, Advisory Board: Roche, Merck Serono, Servier, Pierre Fabre, Pfizer; Financial Interests, Institutional, Research Grant: Merck Serono, Roche, Amgen; Financial Interests, Institutional, Local PI: Pfizer, Pierre Fabre, Servier. E. Martinelli: Financial Interests, Personal, Invited Speaker: Merck-Serono, Bayer, Merck S.p.a, ESMO; Financial Interests, Personal, Writing Engagement, Advisory board and invited speaker and travel grant: Pierre Fabre; Financial Interests, Personal, Writing Engagement, Advisory board and Invited speakers: INCYTE; Financial Interests, Personal, Writing Engagement, Advisory board and invited speaker: Servier, Roche; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Writing Engagement, Travel grant: AstraZeneca; Financial Interests, Personal, Writing Engagement, Advisory board: MSD. All other authors have declared no conflicts of interest.
Resources from the same session
611P - SHR-1701 in combination with BP102 and XELOX as first-line (1L) treatment for patients (pts) with unresectable metastatic colorectal cancer (mCRC): Data from a phase II/III study
Presenter: Rui-Hua Xu
Session: Poster session 10
612P - Updated results from the multicenter phase II study of fruquintinib plus mFOLFOX6/FOLFIRI as first-line therapy in advanced metastatic colorectal cancer (mCRC)
Presenter: fuxiang zhou
Session: Poster session 10
613P - Effect of prior use of anti-VEGF agents on overall survival in patients with refractory metastatic colorectal cancer: A post-hoc analysis of the phase III SUNLIGHT trial
Presenter: Gerald Prager
Session: Poster session 10
614P - Effect of KRASG12 mutations on overall survival in patients with refractory metastatic colorectal cancer: A post-hoc analysis of the phase III SUNLIGHT trial
Presenter: Josep Tabernero
Session: Poster session 10
615P - The impacts of starting regorafenib dose on treatment outcomes in metastatic colorectal cancer
Presenter: Satoshi Yuki
Session: Poster session 10
616P - Sequential treatment with regorafenib (REG) and trifluridine/tipiracil (TAS) +/- bevacizumab (Bev) in refractory metastatic colorectal cancer (mCRC) in community clinical practice in the USA
Presenter: Tanios Bekaii-Saab
Session: Poster session 10
618P - Efficacy and safety of vactosertib and pembrolizumab combination in patients with previously treated microsatellite stable metastatic colorectal cancer
Presenter: Tae Won Kim
Session: Poster session 10
619P - Pelareorep + atezolizumab and chemotherapy in third-line (3L) metastatic colorectal cancer (mCRC) patients: Interim results from the GOBLET study
Presenter: Guy Ungerechts
Session: Poster session 10
621P - The systemic proteome of consensus molecular subtypes from patients with RAS wild-type metastatic colorectal cancer: Analysis from the randomized phase II PanaMa (AIO KRK0212) trial
Presenter: Alexej Ballhausen
Session: Poster session 10