Analysis of the Phase II CONDOR trial Indicates That the immune checkpoint inhibitor durvalumab is tolerable Among heavily pre-treated Patients With recurrent or metastatic head and neck cancer and has the potential to slow growth in tumors With the low or negative expression of the PD-L1 protein.

The previously reported phase II HAWK trial demonstrated the safety and efficacy of durvalumab monotherapy in head and neck tumors that express high levels of PD-L1, and CONDOR (NCT02319044) is the first trial to show similar findings for durvalumab monotherapy in patients with low or negative PD-L1 .

Cancerous cells produces proteins to stop the body's natural immune response to recognize and respond to the disease. Immune checkpoint inhibitors such as durvalumab are designed to block these so-called " checkpoint " proteins-thus allowing the immune system to remain active and attack tumors more successfully.

"Two immunotherapies have already been approved for use in platinum-refractory recurrent or metastatic head and neck cancer, but not all patients respond to these therapies. likely to respond to treatment, "said Lillian Siu, lead author of the study.

"In the phase II CONDOR trial, durvalumab , an investigational PD-L1 inhibitor, showed an overall response rate consistent with other single-agent PD-1 / PD-L1 inhibitors in second-line settings for head and neck cancer," said Siu. , also a professor of medicine at the University of Toronto.

"Our results add to the body of evidence that this immune checkpoint inhibitor is tolerable and has demonstrated encouraging clinical activity across a range of tumors, including in heavily pre-treated recurrent or metastatic head and neck cancer," Siu added.

Findings are based on 267 patients with metastatic (64% of patients) or recurrent (36%) cancer of the oral cavity, oropharynx, hypopharynx or larynx who had not responded to prior platinum-based chemotherapy, and who had low or negative expression of the PD-L1 protein.

Patients were stratified by HPV and smoking status and randomized to one of three treatment arms: durvalumab alone (10 mg / kg, IV Q2W, n = 67); tremelimumab alone (10 mg / kg IV Q4W × 7 then Q12W × 2, n = 67); or durvalumab plus tremelimumab ([20 mg / kg D Q4W + 1 mg / kg T Q4W] × 4 then 10 mg / kg D Q2W, n = 133).

Treatment-related adverse events of any grade were highest for durvalumab alone (63.1% of patients), followed by durvalumab + tremelimumab (57.9%) and tremelimumab alone (55.4%); rates for grade 3 or 4 events, conversely, were highest for tremelimumab (16.9%), followed by durvalumab + tremelimumab (15.8%) and durvalumab (12.3%).

Durvalumab showed encouraging anti-tumor activity both alone and in combination with tremelimumab. Seventeen patients experienced partial responses to treatment, for overall response rates (ORR) of 9.2% for durvalumab alone, 7.8% for durvalumab + tremelimumab and 1.6% for tremelimumab alone.

Median overall survival was 7.6 months for durvalumab + tremelimumab, 6.0 months for durvalumab and 5.5 months for tremelimumab. There was no observed difference in clinical activity between durvalumab alone and durvalumab in combination with tremelimumab.