FDA Grants Priority Review to Durvalumab for Patients With Biliary Tract Cancer


The FDA has granted priority review to a supplemental biologics license application for durvalumab as treatment of patients with locally advanced or metastatic biliary tract cancer.

The FDA has granted priority review to a supplemental biologics license application (sBLA) for durvalumab (Imfinzi) as treatment of patients with locally advanced or metastatic biliary tract cancer, according to AstraZeneca.1

Findings from the phase 3 TOPAZ-1 trial (NCT03875235) which were presented at the American Society of Clinical Oncology 2022 Gastrointestinal Cancers Symposium, support the sBLA for durvalumab.

“People with advanced biliary tract cancer have faced poor outcomes and limited treatment options for too long, and today’s news for the TOPAZ-1 trial underscores the urgency to deliver new, effective therapies in this setting. We are working closely with the FDA to bring the first immunotherapy-based option to patients with this devastating cancer and potentially set a new standard of care with Imfinzi plus chemotherapy,” stated Susan Galbraith, executive vice president, oncology R&D of AstraZeneca, in the press release.

Durvalumab, an anti-PD-L1 therapy, is currently FDA approved for indication in non–small cell lung cancer (NSCLC), and extensive-stage small cell lung cancer (SCLC). Previously in December 2020, durvalumab was also granted orphan drug designation in the US for the treatment of biliary tract cancer. The agent is currently also being developed to treat other SCLC and NSCLC subgroups, bladder cancer, liver cancer, esophageal cancer, gastric cancer, gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, biliary tract cancer, and various other solid tumors.

The ongoing randomized, double-blind placebo controlled, multi-regional, international, TOPAZ-1 study includes 757 patients with unresectable advanced or metastatic BTC, including those with cholangiocarcinoma and gallbladder carcinoma.2

In 145 centers across 17 countries in the United States, Europe, South America, and Asia, patients were enrolled to receive either durvalumab with chemotherapy (gemcitabine and cisplatin) administered by intravenously for up to 8 cycles followed by monotherapy every 4 weeks until disease progression or discontinuation or a matching dose schedule of placebo plus gemcitabine and cisplatin.

The primary end point was overall survival (OS) with secondary end points investigated including duration of response, quality of life, progression-free survival (PFS), overall response rate (ORR), and disease control rate according to PD-L1 expression, serum concentration of durvalumab, and tiered results of anti-drug antibodies for durvalumab.

Eligibility in the study was open to patients aged 18 and older with histologically confirmed disease who were previously untreated with recurrent disease more than 6 months after curative surgery or adjuvant therapy. Other requirements included having a WHO/ECOG performance score of 0 or 1.

Findings showed the experimental combination to have a statistically significant and clinically meaningful improvement in OS compared with chemotherapy alone, and to achieve 2 key secondary end points of the study, improvements in PFS and ORR.

Durvalumab plus chemotherapy to reduce the risk of death by 20% vs with chemotherapy alone (HR, 0.80; 95% CI, 0.66 - 0.97; P = 0.021). Additionally, 25% of patients treated with the combination of durvalumab and chemotherapy were alive at 2 years compared to 10% treated with just chemotherapy.3

Additionally, a 25% statistically significant reduction in the risk of disease progression or death was seen in patients given the durvalumab plus chemotherapy (HR, 0.75; 95% CI, 0.64 - 0.89; P = 0.001). ORR was 26.7% with durvalumab and 18.7% with placebo.

In regard to safety, grade 3 or 4 treatment-related adverse events (TRAEs) occurred in a total of 62.7% of patients who received durvalumab and 64.9% of pts receiving placebo. TRAEs led to discontinuation in 8.9% of patients receiving durvalumab and 11.4% of patients receiving placebo.

Overall, the combination was well tolerated, and the discontinuation rate did not increase due to adverse events compared to chemotherapy alone.

  1. First phase III trial in this setting to show improved overall survival with an immunotherapy added to chemotherapy over standard-of-care chemotherapy alone. AstraZeneca. News Release. May 4, 2022. Accessed May 4, 2022. https://bit.ly/3kFJfdi
  2. 2. Durvalumab or placebo in combination with gemcitabine/cisplatin in patients with 1st line advanced biliary tract cancer (TOPAZ-1) (TOPAZ-1). Clinicaltrials.gov. Accessed May 4, 2022. https://clinicaltrials.gov/ct2/show/NCT03875235
  3. Oh D, He AR, Qin S et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. Presented at: 2022 Gastrointestinal Cancers Symposium; January 20-22, 2022; Virtual. Abstract 378
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