New Combo Proves Highly Effective in Head and Neck Cancer

According to phase 1/2 findings that were presented at the Society for Immunotherapy of Cancer (SITC) 31st Annual Meeting & Associated Programs, the combination of lirilumab with the PD-1 inhibitor Opdivo (nivolumab) resulted in an objective response rate (ORR) of 24.1 percent in patients with squamous cell carcinoma of the head and neck (SCCHN).

In the phase 1/2 study, 29 patients with SCCHN were evaluable for response, of which three had a complete response (10.3 percent) and 4 had a partial response (13.8 percent), two of which were near complete responses with a 80 percent or more reduction in tumor size. The six-month overall survival (OS) rate with lirilumab, a killer-cell immunoglobulin-like receptors (KIRs) inhibitor, plus Opdivo was 90 percent and the 12-month OS rate was 60 percent.

"This is the first report of efficacy with the anti-KIR agent lirilumab in combination with nivolumab in patients with squamous cell carcinoma of the head and neck," said lead investigator Rom Leidner, M.D., a medical oncologist at the Providence Cancer Center. "Lirilumab plus nivolumab demonstrated enhanced clinical activity, particularly in PD-L1—positive tumors and with deep and durable responses observed in some patients"

The phase 1/2 dose-escalation study enrolled 159 total patients across a variety of advanced solid tumors. All patients had progressed or were intolerant to one or more prior therapy. Opdivo was administered at 3 mg/kg every two weeks and lirilumab was given every four weeks in doses ranging from 0.1 mg/kg to 3 mg/kg. The phase 2 dose of lirilumab was established as 3 mg/kg.

The median age of patients enrolled was 60 years (range, 21-85) and the majority were male (61.6 percent). One patient had an ECOG performance status (PS) of two and the remainder were 0 (35.8 percent) or one (63.5 percent). The most commonly enrolled tumor types were melanoma (55 patients), SCCHN (41 patients), and non—small cell lung cancer (37 patients).

The update of findings at the SITC meeting focused specifically on those with SCCHN. In this group specifically, the ECOG PS was primarily 1 (78 percent). The most common tumor locations were the oral cavity (56.1 percent) and pharynx and/or oropharynx (34.1 percent). Most patients had received two prior therapies (41.5 percent), and 26.8 percent had received at least three prior regimens. Overall, 19.5 percent of patients had HPV-positive oropharyngeal cancer.

In addition to the ORR of 24.1 percent, eight patients also had stable disease, for an overall disease control rate of 51.7 percent. Three patients progressed prior to their first scans. None of the patients with HPV-positive cancer responded to the combination.

None of the nine patients with PD-L1-negative disease responded to therapy. In those with PD-L1 expression on at least 1 percent of cells (17 patients), the response rate was 41.2 percent. When looking at PD-L1 expression on 5 percent or more of cells (11 patients), the ORR was 54.5 percent, which was similar to the more than 50 percent expression cutoff (seven patients; ORR, 57.1 percent).

To show the added benefits of lirilumab, the investigators looked at the phase 1/2 data side-by-side with results from the CheckMate-141 study, which was the basis for the FDA approval for single-agent Opdivo as a treatment for patients with SCCHN. In this study, the ORR was 13.3 percent, with a CR rate of 2.5 percent. The response rate in patients with PD-L1-negative tumors was 12.3 percent and for those with a cutoff of at least 1 percent the ORR was 17 percent. The six-month OS rate was 55.6 percent and the 12-month rate was 36 percent.

Across the full study (159 patients), treatment-related adverse events (AEs) of all-grades occurred in 71.7 percent of patients treated with the combination, which was similar to Opdivo monotherapy, Leidner said. The most common AEs were fatigue (20.8 percent), pruritus (18.9 percent), infusion-related reactions (17.6 percent) and rash (16.4 percent). Just 15.1 percent of patients experienced a grade 3/4 treatment-related AE, of which 2.5 percent led to a treatment discontinuation.

"Further evaluation of the safety and efficacy of lirilumab plus nivolumab is ongoing in other tumor types," noted Leidner. "We look forward to continuing the study of this novel combination in patients with advanced platinum-refractory squamous cell carcinoma of the head and neck, which is the seventh-leading cause of cancer globally.”

In addition to head and neck cancer and other solid tumors, lirilumab is also being investigated in combination with Opdivo or azacitidine as a treatment for patients with refractory/relapsed acute myeloid leukemia and myelodysplastic syndromes (NCT02399917, NCT02599649). Additionally, the agent is being assessed with rituximab for patients with high-risk chronic lymphocytic leukemia (NCT02481297).