620P - A phase II trial evaluating the activity of cabozantinib in pre-treated patients with metastatic colorectal cancer (mCRC): ABACO trial initial molecular data

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.