The PD-1 inhibitor cemiplimab (Libtayo) in combination with radiotherapy, cyclophosphamide, and GM-CSF did not demonstrate efficacy superior to other PD-1 inhibitor monotherapies in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to results from a phase I expansion cohort that were presented at the 2018 ESMO Congress.
Treatment for patients with HNSCC has evolved with the introduction of immunotherapy. For example, the anti–PD-1 agents pembrolizumab (Keytruda) and nivolumab (Opdivo) have received FDA approval for the treatment of patients who have progressed on platinum-based chemotherapy, with response rates of 18% and 13%, respectively. However, additional treatment options for this patient population are needed.
In an open-label, multicenter, ascending dose-escalation phase I trial (NCT02383212), investigators are evaluating the use of cemiplimab alone and in combination with other anti-cancer therapies in patients with advanced malignancies.
For the phase I expansion cohort of patients with recurrent or metastatic HNSCC, investigators aimed to evaluate the efficacy, safety, tolerability, and dose-limiting toxicities of the cemiplimab combination regimen.
A total of 15 patients with recurrent/metastatic HNSCC who were refractory to first-line therapy and had disease for which palliative radiotherapy was clinically indicated were enrolled in the phase I expansion cohort. The sub-sites of the head and neck tumors were as follows: oral cavity in 6 patients (40%), hypopharynx in 3 patients (20.0%), oropharynx in 3 patients (20.0%), larynx in 2 patients (13.3%), and oropharyngeal in 1 patient (6.7%).
Patients were eligible to enroll if they were 18 years of age or older, had an ECOG performance status of 0 or 1, had acceptable organ function, and had at least 1 lesion determined to be measurable via RECIST v.1.1 criteria.
Those who had ongoing or recent autoimmune disease and received systemic immunosuppressive treatment, received prior treatment with a PD-1/PD-L1 inhibitor, had brain metastases that had not been treated or could be considered active, had pneumonitis within the past 5 years, received immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks of beginning cemiplimab, or had a known hypersensitivity to GM-CSF or any component that contains yeast-derived products were ineligible for enrollment.
Patients received 3 mg/kg of cemiplimab intravenously (IV) once bi-weekly for up to 48 weeks (up to 6 cycles, with each cycle consisting of 56 days), plus daily 250 μg in the first 7 days of a 2-week cycle for a total of 4 cycles, plus 27 Gy of radiotherapy—9 Gy 3 times over 1 week—starting 1 week after the first dose of cemiplimab, in addition to 300 mg/m2
of IV cyclophosphamide every 14 days for a total of 4 doses. Investigators also performed response assessments every 8 weeks to measure ORR.
At the September 1, 2017, cutoff date, 3 patients (20.0%) were still on treatment, while the majority of patients (n = 12, 80.0%) had discontinued treatment, mostly due to disease progression (n = 8). The median number of doses of cemiplimab administered was 6 (range: 1-19), while the median duration of exposure to the drug was 12.3 weeks (range, 2.0-41.7). In addition, the median duration of follow-up was 3.3 months (range, 0.5-10.2).
Results showed that the median progression-free survival (PFS) in those who received the cemiplimab combination was 1.8 months (95% CI, 1.7-4.7), while the overall tumor response rate was 6.7% (95% CI, 0.2-3.19). One patient experienced a partial response (6.7%), 5 patients had stable disease (33.3%), 7 patients had progressive disease (46.7%), and 2 patients were not evaluable (13.3%).
The safety profile of the cemiplimab combination proved consistent with safety profiles that had been previously reported with cemiplimab monotherapy. No new safety signals were reported.
All-grade treatment-emergent adverse events (TEAEs) were observed in 14 of the 15 patients (93.3%). The most common TEAEs, regardless of attribution, included fatigue (n = 6), constipation (n = 4), asthenia (n = 3), dyspnea (n = 3), maculo-papular rash (n = 3), pneumonia (n = 3, 20.0%), arthralgia (n = 2), decreased appetite (n = 2), dehydration (n = 2), hypokalemia (n = 2), nausea (n = 2), rash (n = 2), stomatitis (n =2), and weight decrease (n = 2).
Six patients (40.0%) experienced serious TEAEs, and the most frequent grade ≥3 TEAE was pneumonia (n = 2, 13.3%). One TEAE—community-acquired pneumonia—resulted in treatment discontinuation (n = 1, 6.7%).
The investigators concluded that the use of cemiplimab in combination with radiotherapy, cyclophosphamide, and GM-CSF did not show greater efficacy than what has been achieved with other PD-1 inhibitor monotherapies in patients with recurrent or metastatic HNSCC.
Babiker H, Brana, I, Mahadevan, D, et al. Phase 1 expansion cohort results of cemiplimab, a human PD-1 monoclonal antibody, in combination with radiotherapy, cyclophosphamide and GM-CSF, in patients with recurrent or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2018;29(suppl):8. Abstract 1171P.