JAVELIN Head and Neck 100 Trial Discontinued Due to Efficacy Doubts

The phase III JAVELIN 100 trial of avelumab (Bavencio) plus chemoradiotherapy (CRT) versus standard-of-care (SOC) CRT in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) has been terminated due to doubt that the combination will meet the primary end point, progression-free survival (PFS), EMD Serano and Pfizer announced in a press release.¹

A detailed analysis of the study is underway and results will be shared at a later date.

The JAVELIN Head and Neck 100 trial was the first initiated to serve an unmet need for additional therapeutic options that can prevent recurrence or the development of metastatic disease in patients with locally advanced HNSCC.

The randomized, double-blind, placebo-controlled, parallel-arm study included 697 patients who had no previous treatment for locally advanced HNSCC who were randomized to receive the experimental combination of avelumab 10 mg/kg intravenously (IV) plus SOC CRT or the control combination of placebo plus SOC CRT. The trial was broken down into 3 segments: the lead-in, CRT, and maintenance phases. During the lead-in, patients received a single dose of avelumab or placebo, followed by concurrent avelumab or placebo with CRT for 7 weeks, and finally avelumab or placebo every 2 weeks for 12 months as maintenance. This was done to activate an immune response during the lead-in and CRT phases and lengthen and sustain immune memory once patients reach the maintenance phase.²

In the study, the PFS primary end point is investigator-assessed per modified RECIST v1.1 criteria. Key secondary end points included overall survival, objective response rate, locoregional failure, distant metastatic failure, and the duration of response. Formal interim analyses of both PFS and overall survival were performed. Other secondary end points included investigator-assessed antitumor activity per modified RECIST v1.1, safety, the pharmacokinetics of avelumab and cisplatin, anti-drug antibodies against avelumab, patient-reported outcomes, candidate biomarker expression of PD-L1, and tumor-infiltrating CD8-positive T cells.

The exploratory end points in JAVELIN Head and Neck 100 included the molecular, cellular, and soluble markers for antitumor response or disease progression and PET scans and pathological testing of neck dissection.

Patients were eligible to enroll in the study given that they were at least 18 years of age and had histologically confirmed locally advanced HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx. Patients were required to have high-risk disease based on human papillomavirus status and tumor stage, not received prior therapy for advanced HNSCC; an ECOG performance status of 0 or 1; adequate renal, hepatic, and hematologic function; and be eligible for treatment with cisplatin.

Individuals were ineligible for JAVELIN Head and Neck 100 if they had prior treatment that targeted T-cell co-stimulation or any immune checkpoint pathways, major surgery or involvement in therapeutic studies within 4 weeks or less prior to randomization, hepatitis B or C infection, prior immunodeficiency requiring therapy, active infection, an autoimmune disease requiring systemic therapy, known hypersensitivity to monoclonal antibodies or drugs used in the study, or a diagnosis of another malignancy within 5 years of randomization.

Avelumab is a human anti—PD-L1 lgG1 antibody, which has shown clinical activity across multiple tumor types. JAVELIN Head and Neck 100 is one of many clinical trials that fall under a global strategic alliance between Merck, and Pfizer, to investigate the potential of avelumab across malignancies.

Thus far, 2 of the studies have been terminated, including the phase III JAVELIN Ovarian PARP 100 trial.³The pivotal JAVELIN Merkel 200 trial is active and showing durable responses in patients with Merkel cell carcinoma.⁴

References

1. EMD serono and Pfizer provide update on phase III JAVELIN Head and Neck 100 study [news release]. Rockland, Massachusetts and New York, New York. EMD Serono, Inc. and Pfizer, Inc. March 13, 2020. https://bit.ly/33doufx. Accessed March 13, 2020.
2. Lee, NY, Ferris, RL, Beck JT, et al. JAVELIN head and neck 100: A phase 3 trial of avelumab in combination with chemoradiotherapy (CRT) vs CRT for 1st-line treatment of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Poster presented at: 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, IL. Abstract TPS6093.
3. 3. MERCK kgaa, darmstadt, germany, and Pfizer announce discontinuation of phase III JAVELIN Ovarian Parp 100 trial in previously untreated advanced ovarian cancer [news release]. Rockland, Massachusetts and New York, New York: Merck and Pfizer, Inc. March 19, 2019. https://bit.ly/2W9YiRp. March 13, 2020.
4. Two-year update of pivotal javelin merkel 200 trial shows continued durable responses with bavencio® (avelumab) [news release]. Rockland, Massachusetts and New York, New York: Merck and Pfizer, Inc. June 4, 2018.https://bit.ly/2xtuF34. Accessed March 13, 2020.