WASHINGTON – and associated with deep and durable responses in patients with recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck, according to data from an ongoing cohort expansion study.
As of Aug. 21, 2018, the primary study endpoint of overall response rate in 40 evaluable patients enrolled in the single-arm, nonrandomized phase 1/2 study was 27.5%, Roger Cohen, MD, reported at the annual meeting of the Society for Immunotherapy of Cancer.
There were 11 confirmed responses, including 1 complete response and 10 partial responses at a median follow-up of 8 months, said, a professor of medicine at the Hospital of the University of Pennsylvania and director of clinical research at the Abramson Cancer Center, Philadelphia.
Median progression-free survival and overall survival were 5.0 months and 10.3 months, respectively.
“We observed responses in patients who were naive to immunotherapy, as well as patients who had received and progressed after immunotherapy. We observed responses in patients who were platinum resistant, and we also saw responses in [human papillomavirus (HPV)]–positive and –negative patients,” he said, adding that responses occurred relatively early at a median of 1.6 months, and that there was little difference between those who had and had not received prior immunotherapy with programmed death-1 (PD-1) antibodies.
A number of the responses, as well as the stable diseases, were durable for “a considerable period of time.” The median duration of response was 5.6 months, he said.
Study participants were mainly middle-aged men with recurrent or metastatic HPV-positive or -negative advanced disease and “decent” performance status. They received monalizumab at a dose of 10 mg/kg every 2 weeks plus cetuximab at the labeled loading dose of 400 mg/m2 once weekly then 250 mg/m2 once weekly. All had progressed after prior platinum-based chemotherapy and had no more than two prior lines of therapy in the recurrent/metastatic setting; 17 (43%) had prior anti–programmed death-ligand 1 (PD-L1) therapy, 5 (13%) had prior cetuximab, but none of those patients were cetuximab resistant.
They were treated until disease progression or unacceptable toxicity and were assessed every 8 weeks for response per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, he said.
This treatment combination was shown in the phase 1 portion of the study to have a favorable safety profile, and the safety profile was confirmed in this expansion cohort; adverse events related to the combination were dominated by EGFR antibody–related side effects in the skin, as well as hypomagnesemia. Most adverse events associated with monalizumab were grade 1-2.
“Serious adverse events are in the single digits,” Dr. Cohen said.
Monalizumab is a first-in-class humanized immunoglobulin-G4 monoclonal antibody against the human natural killer group 2A (NKG2A), which is the receptor for the NKG2A ligand, HLA-E.
“The HLA-E NKG2A diad shuts down NK cells and tumor-infiltrating CD8-positive T-cells,” he explained, adding that “the concept behind the antibody is that by blocking the interaction of the receptor for the ligand you can reduce this inhibitory signaling by NK cells and thereby unleash their ability to target tumor.”
Cetuximab is an established and approved EGFR inhibitor for the treatment of patients with head and neck SCC who progress after platinum-based chemotherapy. It has been associated with a 13% response rate.
“The therapeutic hypothesis is that dual targeting with these two antibodies will allow us to realize greater antitumor activity in head and neck cancer than is seen with cetuximab alone,” he said, later adding that “the combination of monalizumab and cetuximab results in early, deep, and durable responses in patients with squamous cell cancer of the head and neck ... and the activity indeed is higher than cetuximab alone, compared with historical data.”
Additionally, the safety is acceptable, and preliminary translational analyses do show some immunological proof-of-concept – mainly that infiltration of the tumor stroma with NK and CD8-positive T cells is correlated with response, he said.
“Importantly, this study is continuing to enroll patients, and taking account of the ever-changing landscape in the treatment of patients with advanced cancer, we are going to enroll another 40 patients, except this time we will require them to be platinum, as well as PD-1 antibody exposed. These patients still represent an enormous unmet medical need.
“We think these results do warrant further development of the combo of monalizumab and cetuximab in patients with advanced SCC of the head and neck,” he concluded.
Dr. Cohen reported receiving consulting fees and/or research funding from Cantargia, Celldex, Genocea, Innate, HEAT, Kyntherapeutics, Merck, Takeda Macrogenics, and Tmunity.
SOURCE: Cohen R et al. SITC 2018, .