FDA Grants Durvalumab Orphan Drug Status in Small Cell Lung Cancer

The FDA has granted an Orphan Drug Designation to durvalumab for the treatment of patients with small cell lung cancer, according to AstraZeneca, the developer of the PD-L1 inhibitor.

José Baselga, MD

The FDA has granted an Orphan Drug Designation to durvalumab (Imfinzi) for the treatment of patients with small cell lung cancer (SCLC), according to AstraZeneca, the developer of the PD-L1 inhibitor.1

The designation follows the announcement of the phase III CASPIAN trial data, in which the combination of durvalumab and standard etoposide and platinum-based chemotherapy showed a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy alone for patients with extensive-stage SCLC.2 Results of the study will be presented at an upcoming medical meeting.

“This Orphan Drug Designation comes on the heels of positive results from the phase III CASPIAN trial, which is the first trial to offer the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer,” José Baselga, MD, executive vice president, R&D Oncology, AstraZeneca, stated in a press release. “We are eager to expand treatment options for patients facing such a devastating diagnosis and look forward to working with regulatory authorities to bring forward new options as soon as possible.”

SCLC, which comprises approximately 15% of all lung cancer diagnoses, has a poor prognosis with an estimated 5-year OS rate of 6%. Orphan Drug Designation status is granted to current and emerging therapies intended for the treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States.

In the international, multicenter, open-label, phase III CASPIAN study, 988 treatment-naïve patients with extensive-stage SCLC were randomized 1:1:1 to durvalumab plus etoposide and either cisplatin or carboplatin, durvalumab plus the CTLA-4 inhibitor tremelimumab and chemotherapy, or chemotherapy alone. In both experimental arms, patients received ≤4 cycles of chemotherapy, while the control arm permitted ≤6 cycles of chemotherapy and prophylactic cranial irradiation.

In the durvalumab arms, the PD-L1 inhibitor is given intravenously every 3 weeks for four 12-week cycles, and every 4 weeks thereafter until progressive disease or treatment discontinuation. In the durvalumab/tremelimumab arm, the CTLA-4 inhibitor is given IV every 3 weeks for four 12-week cycles, and an additional dose is given in week 16.

Those enrolled on the trial were adult patients aged ≥18 years with histologically or cytologically documented stage IV extensive-stage SCLC, based on the American Joint Committee on Cancer Stage 7th edition. Patients must also have a World Health Organization/ECOG performance status of 0 or 1.

If patients had a history of radiation to the chest prior to systemic therapy or had planned consolidation chest radiation therapy; paraneoplastic syndrome of autoimmune nature; active infection with tuberculosis, HIV, hepatitis B and C; active or prior autoimmune or inflammatory disorders; or uncontrolled intercurrent illness, they were excluded from enrollment.

The trial’s primary endpoint was OS; secondary endpoints included progression-free survival (PFS), overall response rate, 6- and 12-month PFS rates, 18-month OS rate, quality of life, pharmacokinetics, and pharmacodynamics. Safety was also assessed as another outcome measure.

Patients were assessed at time of screening as a baseline, with follow-ups at week 6 ±1 week from the date of randomization, at week 12 ±1 week from the date of randomization, and then every 8 weeks ±1 week until disease progression. The safety and tolerability of the dosing and schedule from the experimental arms are reviewed via an Independent Data Monitoring Committee at two early stages of enrollment.

The study is being conducted in more than 200 institutions across 22 countries. AstraZeneca previously stated that the safety and tolerability findings of the immunotherapy/chemotherapy combination were consistent with the safety profile of each agent alone.

The PD-L1 inhibitor is currently being evaluated in the phase III ADRIATIC trial, which is looking at the agent following concurrent chemoradiation therapy in patients with limited-stage SCLC.

Durvalumab is currently approved for the treatment of patients with unresectable, stage III non—small cell lung cancer following chemotherapy and radiation therapy in more than 45 countries including the United States, European Union, and Japan.


  1. Imfinzi Granted US Orphan Drug Designation for Small Cell lung cancer. AstraZeneca. Published July 12, 2019. https://bit.ly/32lVIIE. Accessed July 12, 2019.
  2. Imfinzi Improves Overall Survival at Interim Analysis in the Phase III CASPIAN Trial in 1st-Line Extensive-Stage Small Cell Lung Cancer. AstraZeneca. Published June 27, 2019. https://bit.ly/2RFpKlz. Accessed June 27, 2019.