On May 19, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported results from a randomized confirmatory Phase 2 study of ficlatuzumab as a single agent or in combination with cetuximab (ERBITUX), an EGFR-targeted antibody, in patients who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab (pan-refractory) with metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, AVEO, MAY 19, 2021, View Source [SID1234580271]). Ficlatuzumab is AVEO’s potent humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets hepatocyte growth factor (HGF). The results will be presented by lead investigator Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Deputy Director, University of Arizona Cancer Center, at a poster discussion session of the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held June 4-8 in a virtual setting.
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"Human papillomavirus (HPV) negative HNSCC is associated with poorer outcomes compared to HPV positive disease, particularly in pan-refractory disease, where there are currently no effective treatment options," said Professor Bauman. "Crosstalk between EGFR and HGF/cMet pathways is a known tumor intrinsic resistance mechanism, and HGF expression is known to be high in HPV negative disease, suggesting that the simultaneous inhibition of these pathways with cetuximab and ficlatuzumab could enhance anti-cancer response in this population. Results from this study are highly encouraging, with notable activity in pan-refractory, HPV negative disease warranting Phase 3 investigation."
"Results in patients with HPV negative disease who received ficlatuzumab and cetuximab produced prolonged progression free survival (PFS) and a response rate of 38%, which included two (18%) complete responses (CRs). These results suggest the combination has the potential to play a meaningful role in the treatment and the ultimate quality of life of patients with relapsed/metastatic HNSCC," said Michael Bailey, president and chief executive officer of AVEO. "The results compare favorably to historical controls of cetuximab in earlier lines of treatment. After receiving FDA feedback, we look forward to making a go/no-go decision by mid-year on the initiation of a Phase 3 study in an HPV negative HNSCC patient population, which we would expect to initiate in the first half of 2022, upon the availability of clinical drug supply."
In the Phase 2 study, a total of 60 patients with metastatic HNSCC who relapsed or were refractory to prior immunotherapy, chemotherapy, and cetuximab were randomized 1:1 to receive either ficlatuzumab alone (20 mg/kg IV) or ficlatuzumab in combination with cetuximab (500 mg/m2 IV) every two weeks. The ficlatuzumab/cetuximab combination arm met the study’s primary endpoint of median PFS, with the 32 evaluable patients in the arm demonstrating a median PFS of 3.6 months (lower bound 90% confidence interval [CI] 2.3 months; p=0.04), and 1.8 months (lower bound 90% CI: 1.7 months) for the 26 evaluable patients receiving ficlatuzumab alone. For the key secondary endpoint of overall response rate (ORR), the combination arm demonstrated an ORR of 19%, and 4% for ficlatuzumab alone.
Enrolled patients were stratified by HPV status, as HPV negative patients are known to have poorer outcomes. In an exploratory comparison of the HPV positive (n=16) and HPV negative (n=16) subgroups of the combination arm, HPV negative patients demonstrated both a superior ORR of 38% (versus 0% for HPV positive, p=0.02), with two CRs and four partial responses, and a median PFS of 4.1 months (versus 2.3 months for HPV positive, p=0.03). These results reflect updated data from those available at the time of abstract submission.
The combination of ficlatuzumab and cetuximab was generally well-tolerated with expected class toxicities from HGF/cMet inhibitors observed, including common adverse events of edema and hypoalbuminemia, and an uncommon adverse event of pneumonitis. Two treatment related deaths occurred, including pneumonitis (ficlatuzumab arm) and cardiopulmonary arrest (combination arm).
A copy of the poster will be available at www.aveooncology.com after its presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.
ASCO Presentation Details
Title: Randomized Phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).
Presenter: Julie E. Bauman, M.D., MPH, Professor of Medicine, Chief, Division of Hematology/Oncology, Associate Director of Translational Research, University of Arizona Cancer Center
Abstract: 6015
Track: Head and Neck Cancer
Date and Time: June 4, 2021 at 9:00 a.m. Eastern Time
About Ficlatuzumab
Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) immunoglobulin G1 (IgG1) inhibitory antibody that binds to the HGF ligand with high affinity and specificity. HGF is the natural ligand of c-Met and blocking HGF inhibits signaling through the HGF/c-Met signaling pathway. Ficlatuzumab is currently being evaluated in squamous cell carcinoma of the head and neck (HNSCC) and metastatic pancreatic ductal cancer (PDAC).