AVEO Oncology Announces Positive Results from Randomized Phase 2 Study of Ficlatuzumab in Combination with Cetuximab in Pan-Refractory, Metastatic HNSCC
– Study Achieved Primary Endpoint of mPFS in Patients Treated with Ficlatuzumab/Cetuximab (ERBITUX®) Combination –
– 38% ORR, Including 13% CRs and 25% PRs, and Median PFS of 4.1 months Observed in HPV Negative Patients Treated with Ficlatuzumab/Cetuximab Combination –
– Phase 3 Go/No-Go Decision Expected After FDA Feedback –
– Results to be Presented at the 2021 ASCO Annual Meeting –
“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
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 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).
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, 2021at 9:00 a.m. Eastern Time
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).
AVEO is an oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for cancer patients. AVEO’s strategy is to focus its resources toward the development and commercialization of its product candidates in
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements of AVEO within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. The words “anticipate,” “believe,” “design,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “could,” “should,” “would,” “seek,” “look forward,” “advance,” “goal,” “strategy,” or the negative of these terms or other similar expressions, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, among others, statements about: the potential for ficlatuzumab as a treatment option for patients with HPV negative HNSCC; the potential efficacy, safety, and tolerability of ficlatuzumab, both as a stand-alone drug candidate and in combination with other therapies in HPV negative HNSCC and other indications; AVEO’s execution of its clinical and regulatory strategy for ficlatuzumab; AVEO’s plans and strategies for current and future clinical trials of tivozanib, ficlatuzumab and AV-380 and for commercialization of FOTIVDA in
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Source: AVEO Oncology