On September 2, 2022, the U.S. Food and Drug Administration (FDA) approved durvalumab (Imfinzi®) in combination with gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancer (BTC).

FDA Approves Durvalumab for Locally Advanced or Metastatic Biliary Tract Cancer

Efficacy was evaluated in TOPAZ-1 (NCT03875235), a randomized, double-blind, placebo-controlled, multiregional trial that enrolled 685 patients with histologically confirmed locally advanced unresectable or metastatic BTC who had not previously received systemic therapy for advanced disease.

Patients’ median age was 64 years (range = 20–85) and 47% were aged 65 years or older. Among the study participants, 56% were Asian, 50% male, 37% White, 7% Hispanic or Latino, 4% other race, and 2% Black. Fifty-six percent had intrahepatic cholangiocarcinoma, 25% had gallbladder cancer, and 19% had extrahepatic cholangiocarcinoma.

Patients were randomized 1:1 to receive:

  • Durvalumab 1,500 mg on day 1 plus gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of each 21-day cycle up to 8 cycles, followed by durvalumab 1,500 mg every four weeks, or
  • Placebo on day 1 plus gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of each 21-day cycle up to 8 cycles, followed by placebo every four weeks.

Patients continued durvalumab or placebo until they experienced disease progression or unacceptable toxicity. Treatment was permitted beyond disease progression for patients who were clinically stable and deriving clinical benefit, as determined by the investigator.

The major efficacy outcome measure was overall survival (OS). Tumor assessments were conducted every six weeks for the first 24 weeks, and then every 8 weeks until patients experienced confirmed objective disease progression. Patients randomized to receive durvalumab with gemcitabine and cisplatin demonstrated a statistically significant improvement in OS compared to those randomized to receive placebo with gemcitabine and cisplatin. Median OS was 12.8 months (95% CI = 11.1, 14) and 11.5 months (95% CI = 10.1, 12.5) in the durvalumab and placebo arms, respectively (hazard ratio = 0.80; 95% CI = 0.66, 0.97, p = 0.021). Median progression-free survival was 7.2 months (95% CI = 6.7, 7.4) and 5.7 months (95% CI = 5.6, 6.7) in the durvalumab and placebo arms, respectively. Investigator-assessed overall response rate was 27% (95% CI = 22%–32%) and 19% (95% CI = 15%–23%) in the durvalumab and placebo arms, respectively.

The most common adverse reactions reported in at least 20% of patients were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.

The recommended durvalumab dose is 1,500 mg every three weeks for patients with a body weight of at least 30 kg when given with gemcitabine and cisplatin, followed by 1,500 mg every four weeks as a single agent until patients experience disease progression or unacceptable toxicity. For patients with a body weight of less than 30 kg, the recommended dose is 20 mg/kg every three weeks with gemcitabine and cisplatin followed by 20 mg/kg every four weeks until patients experience disease progression or unacceptable toxicity.

View the full prescribing information for durvalumab.

The review was conducted under Project Orbis, an initiative of FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Singapore’s Health Sciences Authority, and Switzerland’s Swissmedic. The application reviews may be ongoing at the other regulatory agencies.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

The application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. The application also was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.