Oncology News Burst from FDA

September 8, 2022 Oncology News Burst from FDA: durvalumab approved for locally advanced or metastatic biliary tract cancer >

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

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.

Trial demographics were as follows: 56% Asian, 37% White, 2% Black, and 4% other race; 7% Hispanic or Latino; 50% male and 50% female; median age was 64 years (range 20-85) and 47% were 65 years or older. 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+ 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 4 weeks, or
  • placebo on Day 1+ 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 4 weeks.

Durvalumab or placebo were continued until disease progression or unacceptable toxicity. Treatment was permitted beyond disease progression if the patient was 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 6 weeks for the first 24 weeks, then every 8 weeks until confirmed objective disease progression. A statistically significant improvement in OS was demonstrated in patients randomized to receive durvalumab with gemcitabine and cisplatin 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). The 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 (≥20%) adverse reactions occurring in patients were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.

The recommended durvalumab dose is 1,500 mg every 3 weeks for patients with a body weight ≥30 kg when given with gemcitabine and cisplatin, followed by 1,500 mg every 4 weeks as a single agent until disease progression or unacceptable toxicity. For patients with a body weight <30 kg, the recommended dose is 20 mg/kg every 3 weeks with gemcitabine and cisplatin followed by 20 mg/kg every 4 weeks until disease progression or unacceptable toxicity.

View full prescribing information for Imfinzi.

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

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

This 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 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncology


July 27, 2022 Oncology News Burst from FDA: pembrolizumab >

On March 4, 2022, the Food and Drug Administration approved nivolumab (Opdivo, Bristol-Myers Squibb Company) with platinum-doublet chemotherapy for adult patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting.

This represents the first FDA approval for neoadjuvant therapy for early-stage NSCLC.

Efficacy was evaluated in CHECKMATE-816 (NCT02998528), a randomized, open label trial in patients with resectable, histologically confirmed Stage IB (≥4 cm), II, or IIIA NSCLC (AJCC/UICC staging criteria) and measurable disease (RECIST v1.1.). Patients were enrolled regardless of the tumor PD-L1 status. A total of 358 patients were randomized to receive either nivolumab plus platinum-doublet chemotherapy administered every 3 weeks for up to 3 cycles, or platinum-chemotherapy alone administered on the same schedule.

The main efficacy outcome measures were event-free survival (EFS) and pathologic complete response (pCR) by blinded independent central review. Median EFS was 31.6 months (95% CI: 30.2, not reached) in the nivolumab plus chemotherapy arm and 20.8 months (95% CI: 14.0, 26.7) for those receiving chemotherapy alone. The hazard ratio was 0.63 (97.38% CI: 0.43, 0.91; p=0.0052). The pCR rate was 24% (95% CI: 18.0, 31.0) in the nivolumab plus chemotherapy arm and 2.2% (95% CI: 0.6, 5.6) in the chemotherapy alone arm.

The most common adverse reactions (incidence ≥20%) occurring in patients were nausea, constipation, fatigue, decreased appetite, and rash. The addition of nivolumab to chemotherapy did not result in more frequent delays or cancellations of surgery. The median lengths of hospital stays following definitive surgery and the rates of adverse reactions identified as surgical complications were similar for patients in both arms of the trial.

The recommended nivolumab dose is 360 mg with platinum-doublet chemotherapy on the same day every 3 weeks for 3 cycles.

View full prescribing information for Opdivo.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews may be ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application five months ahead of the FDA goal date.

This 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.

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 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer.