ASCO24: Gilead, Arcus' etrumadenant extends survival in refractory colorectal cancer
24 May 2024
ASCOClinical ResultPhase 2
Arcus Biosciences' etrumadenant, an oral adenosine receptor antagonist that has fallen short in previous trials, could get a new lease on life after showing promising survival benefits in a Phase II study in metastatic colorectal cancer (mCRC).
Data from the ARC-9 study, revealed in Thursday's abstract drop ahead of the American Society of Clinical Oncology (ASCO) conference later this month, suggested the drug together with the experimental anti-PD-1 antibody zimberelimab plus standard chemotherapy may help mCRC patients live significantly longer without disease progressing.
Etrumadenant, partnered with Gilead Sciences, was deprioritised in prostate cancer last August due to lack of clinical benefit in the Phase II ARC-6 study, and prior to that also had its third-line EGFR-mutant non-small-cell lung cancer programme shelved after failing to show "differentiated clinical activity" in the early-stage ARC-4 trial.
Cohort B of the ARC-9 study has enrolled 112 mCRC patients who progressed on both oxaliplatin- and irinotecan-containing regimens. Participants were randomised to receive either a combination consisting of etrumadenant, zimberelimab plus FOLFOX/bevacizumab or Bayer's Stivarga (regorafenib) administered as part of standard chemotherapy regimen.
OS benefit of almost 10 months
With a median follow-up of 20.4 months, the etrumadenant arm demonstrated a 73% improvement in progression-free survival (PFS) versus Stivarga, meeting the study's primary endpoint. Median PFS was 6.2 months and 2.1 months, respectively. There was also a 63% improvement on the key secondary goal of overall survival (OS) compared to Stivarga, with patients surviving a median 19.7 months and 9.5 months, respectively.
On the safety front, Grade ≥3 treatment-emergent adverse events (TEAEs) were more frequent in the etrumadenant arm at over 82%, versus nearly 49% with Stivarga, although TEAEs leading to discontinuations were more likely with Stivarga, where the rate was roughly 17%, compared to 5.4% for etrumadenant.
During the company's recent earnings call, CEO Terry Rosen highlighted the ARC-9 data as further validating the adenosine pathway as an important therapeutic target in oncology.
Between ARC-8, which evaluated Arcus' CD73 inhibitor small molecule quemliclustat in combination with chemotherapy in first-line pancreatic cancer, MORPHEUS-PDAC, which evaluated etrumadenant with chemo in first-line pancreatic cancer, "and now ARC-9, we have three independent, but similar datasets which together provide compelling evidence demonstrating that mitigating the immunosuppressive action of adenosine combined with immunogenic chemotherapy may prolong survival relative to…chemotherapy alone," he said.
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