VEO Oncology Announces Positive Results from Randomized Phase 2 Study of Ficlatuzumab in Combination with Cetuximab in Pan-Refractory, Metastatic HNSCC

BOSTON – AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, today announced 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). 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, Associate Director of Translational Research, Deputy Director, University of Arizona Cancer Center, at a poster discussion session of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held June 4-8 in a virtual setting.

“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 Michael Needle, M.D., Chief Medical Officer of AVEO. “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 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).
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).

About AVEO Pharmaceuticals, Inc.

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 North America, while leveraging partnerships to support development and commercialization in other geographies. AVEO’s lead candidate, FOTIVDA® (tivozanib), received U.S. Food and Drug Administration (FDA) approval on March 10, 2021 for the treatment of adult patients with relapsed or refractory renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA® was approved in August 2017 in the European Union and other countries in the EUSA territory for the treatment of adult patients with advanced RCC. AVEO has previously reported promising clinical data on ficlatuzumab (anti-HGF IgG1 mAb) in head and neck cancer squamous cell carcinoma (HNSCC), pancreatic cancer and acute myeloid leukemia, and expects to make a go/no-go decision on the initiation of a pivotal Phase 3 study of ficlatuzumab in HPV negative HNSCC following feedback from the FDA. AVEO’s pipeline of product candidates also includes AV-380 (anti-GDF15 IgG1 mAb). AVEO has previously reported the acceptance of its investigational new drug application in the U.S. for AV-380 and its initiation of a Phase 1 clinical trial for the potential treatment of cancer cachexia. AVEO’s earlier-stage pipeline includes monoclonal antibodies in oncology development, including AV-203 (anti-ErbB3 mAb) and AV-353 (anti-Notch 3 mAb). AVEO is committed to creating an environment of diversity and inclusion.


¹Pawlowski N et al. AACR 2013. Poster 3971
²J Angulo and O Shapiro, Cancers (Basel) 2019 Sep; 11(9): 1227. [10.3390/cancers11091227]
³Decision Resources. RCC landscape and forecast. December 12, 2019.

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