Imfinzi Seen to Safely Help Certain Patients with Advanced Head and Neck Cancer in Phase 2 Trial

Imfinzi Seen to Safely Help Certain Patients with Advanced Head and Neck Cancer in Phase 2 Trial

Data from the Phase 2 CONDOR trial continue to support the safety, and show some efficacy, of treatment with Imfinzi (durvalumab) in certain pre-treated patients with advanced head and neck cancer.

The findings also suggest that the therapy can slow the growth of tumors that lack or express very little PD-L1 protein — a marker that predicts response to immune checkpoint inhibitors like Imfinzi. It was the first such finding for this treatment in patients with little or no PD-L1.

The results were presented at the recent Multidisciplinary Head and Neck Cancers Symposium in Scottsdale, Arizona. The poster was titled, “A Randomized, Open-Label, Multicenter, Global Phase 2 Study of Durvalumab (D), Tremelimumab (T), or D Plus T, in Patients With PD-L1 Low/Negative Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: CONDOR.”

Cancer cells increase the expression of programmed death-ligand 1 (PD-L1) to escape immune system attacks. Therapeutics that block PD-L1 — such as Imfinzi, being developed by AstraZeneca — reduce tumor growth by stimulating immune activity.

The CONDOR trial (NCT02319044) enrolled 267 people with advanced head and neck cancers — those of the oral cavity, oropharynx, hypopharynx or larynx — who had failed to respond to prior platinum-based chemotherapy. In the majority of patients (64%), the cancer had already spread (metastatic). All had very low or lacked the expression of PD-L1.

Patients were categorized according to prognostic factors, including human papillomavirus (HPV) and smoking status, before being randomized to one of three treatments — Imfinzi alone (67 people), tremelimumab alone (67), or Imfinzi plus tremelimumab (133).

Tremelimumab (developed by MedImmune) is also an immune checkpoint inhibitor, but it targets the CTLA-4 molecule. Medicines targeting the PD-L1 and CTLA-4 molecules have been shown to activate the immune system in different ways. Their combination is thought to increase anti-tumor responses.

Imfinzi showed anti-tumor activity administered either alone or in combination with tremelimumab.

After a median follow-up of 5.8 months, 17 patients showed a decrease in tumor burden (partial response) in response to treatment. Response rates were 9.2% for Imfinzi, 7.8% for Imfinzi plus tremelimumab, and 1.6% for tremelimumab alone.

Overall survival rates were also somewhat extended when Imfinzi was given alone — 7.6 months — compared to Imfinzi plus tremalimumab or tremalimumab alone: 6.0 months and 5.5. months, respectively. This suggests that combining Imfinzi with tremelimumab has no additional positive effects compared to Imfinzi alone.

The safety profile of Imfinzi and tremelimumab was similar to other immunotherapies. Patients who received Imfinzi had a higher percentage of treatment-related adverse effects (63.1%) compared to 57.9% and 55.4% for the combination and tremelimumab alone, respectively.

However, severe adverse effects (grade 3 or 4) affected more patients treated with tremelimumab (16.9%), compared to those who received Imfinzi plus tremelimumab (15.8%), or Imfinzi alone (12.3%).

Twelve people left the trial due to treatment-related adverse events — seven in the combination arm and five in the tremelimumab arm. One death in the combination group was associated with treatment.

“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. For immunotherapy to increase its clinical utility, it’s important that we can better identify the patients who will most likely respond to treatment,” Lillian Siu, MD, the trial’s lead author and a medical oncologist at Princess Margaret Cancer Centre in Toronto, Ontario, said in a press release.

“In the phase II CONDOR trial, durvalumab [Imfinzi], 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,” Siu said. “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.”