Additionally, the response rate with durvalumab was almost double that of placebo (28.4% vs 16.0%; P < .001). Patients assigned to durvalumab also had a significantly longer time to distant metastasis or death compared with placebo (23.2 months vs 14.6 months; P < .001).
Several ongoing clinical trials are also evaluating durvalumab as a single agent or in combination with other therapies, such as tremelimumab, and as a first-line therapy.
A phase 1/2 study (ClinicalTrials.gov Identifier: NCT01693562) used a standard 3+3 dose-escalation phase for durvalumab in patients with advanced solid tumors. Updated results in patients with NSCLC showed that durvalumab had a tolerable safety profile with clinical activity seen in patients with high PD-L1 expression, who had a median overall survival of 21.0 months.3
But early results from the phase 3 MYSTIC trial (ClinicalTrials.gov Identifier: NCT02453282) showed that the study, which tested durvalumab with or without tremelimumab compared with platinum-based standard of care chemotherapy, failed to meet its primary endpoint of PFS.4 Overall survival data are still awaited.
Other clinical trials of durvalumab are still recruiting and include:
- NEPTUNE (ClinicalTrials.gov Identifier: NCT02542293) – first-line durvalumab with tremelimumab vs standard of care for NSCLC
- POSEIDON (ClinicalTrials.gov Identifier: NCT03164616) – first-line comparison of durvalumab plus tremelimumab with chemotherapy, durvalumab with chemotherapy, or chemotherapy alone
- Caspian (ClinicalTrials.gov Identifier: NCT03043872) – first-line durvalumab with or without tremelimumab in combination with platinum-based chemotherapy in extensive-stage small-cell lung cancer
Durvalumab is also being assessed in combination with tremelimumab in phase 3 trials of metastatic urothelial carcinoma and head and neck squamous cell carcinoma, and in early phase studies in hepatocellular carcinoma and several hematologic malignancies.
- Imfinzi granted Breakthrough Therapy Designation by US FDA for patients with locally-advanced unresectable non-small cell lung cancer [news release]. AstraZeneca: July 31, 2017. https://www.astrazeneca.com/media-centre/press-releases/2017/imfinzi-granted-breakthrough-therapy-designation-by-us-fda-for-patients-with-locally-advanced-unresectable-non-small-cell-lung-cancer-31072017.html. Accessed October 23, 2017.
- Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage iii non–small-cell lung cancer. N Engl J Med. 2017 Sep 8. doi: 10.1056/NEJMoa1709937 [Epub ahead of print]
- Antonio SJ, Brahmer JH, Balmanoukian AS, et al. Safety and clinical activity of first-line durvalumab in advanced NSCLC: updated results from a phase 1/2 study. J Clin Oncol. 2017;35(suppl; abstr e20504).
- AstraZeneca reports initial results from the ongoing MYSTIC trial in stage IV lung cancer [news release]. AstraZeneca: July 27, 2017. https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-reports-initial-results-from-the-ongoing-mystic-trial-in-stage-iv-lung-cancer-27072017.html. Accessed October 23, 2017.