Durvalumab: Previous Findings and Current Research

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.

References

1. 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.
2. 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]
3. 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).
4. 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.