Durvalumab, an experimental immunotherapy drug, may be a potential treatment approach for patients with advanced lung or head and neck cancers, according to preliminary data from a Phase 1/2 trial.
Preliminary safety and efficacy data showing promising overall response and overall survival rates were recently presented at the European Society for Medical Oncology 2016 Congress in Denmark.
“We are presenting encouraging early preliminary data for patients with lung or head and neck cancers at this year’s congress,” David Berman, senior vice president, head of Oncology Innovative Medicines at MedImmune, said in a press release. “From efficacy data for durvalumab monotherapy in pre-treated patients to the results of our early-phase trials in combination with novel small-molecule medicines, we have signalled our commitment to finding treatments for patients with these aggressive cancers.”
Durvalumab is an investigational human monoclonal antibody that targets the PD-L1 molecule, impairing its interaction with both PD-1 and the CD80 ligand found at the surface of T-cells. By inhibiting this interaction, durvalumab enhances T-cell responses against the tumor cells, and counters their immune system evasion mechanisms.
The U.S. Food and Drug Administration granted durvalumab Fast Track Designation as a possible treatment of PD-L1-positive patients with mestastatic head and neck squamous cell carcinoma (HNSCC) in 2015, and designated it a Breakthrough Therapy for PD-L1-positive patients with advanced urothelial bladder cancer who had progressed following one planinum-based therapy in 2016.
Now, follow-up data from the Phase 1/2 1108 trial (NCT01693562) evaluating durvalumab in patients with advanced solid tumor has shown promising results in two patient subgroups: people with advanced non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC).
The NSCLC study cohort enrolled 287 patients who had received at least one prior line of therapy and evaluated durvulumab as a monotherapy. Patients with high PD-L1 expressing tumors were found to have better response rates to therapy, showing an overall response rate of 25 percent, compared to only 6 percent in the low PD-L1 expression group.
Consistently, six-month overall survival was also higher in patients with high PD-L1 expression. Indeed, those who had received one, two, or at least three prior lines of therapy and had high PD-L1 expression showed six-month overall survival of 80%, 69%, and 66%, respectively. In those with low PD-L1 expression, however, six-month overall survival rates were 56%, 66%, and 53%, respectively.
Durvalumab’s safety profile was consistent with that observed in prior studies, with the most frequent adverse events being fatigue, reduced appetite, and diarrhea.
In the HNSCC study cohort, durvalumad was assessed in 62 patients who had metastatic or recurrent HNSCC. Overall response rate was 11 percent in all evaluable patients, but higher in those with high PD-L1 expression (18%). Six-month and 12-month overall survival in all evaluable patients was 62% and 42%, respectively. The most common adverse events were fatigue, diarrhea, nausea, and rash, with 8 percent of patients experiencing grade 3 or grade 4 adverse events.