Fouad Namouni, MD
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended adding the option of a 4-week dosing schedule to the label for nivolumab (Opdivo) for the treatment of patients with advanced melanoma and previously treated renal cell carcinoma (RCC).1
The committee is recommending approval of a 4-week dosing regimen with 480 mg of nivolumab for these indications. The panel has also issued its support for replacing weight-based dosing with 240 mg every 2 weeks for the 6 nivolumab monotherapy indications approved in the European Union (EU)—melanoma, non–small cell lung cancer (NSCLC), RCC, classical Hodgkin lymphoma, head and neck squamous cell carcinoma (HNSCC), and urothelial carcinoma.
Bristol-Myers Squibb’s (BMS’s) Marketing Authorization Application will now go to the full European Commission. If approved, these dosing options will be available throughout the EU.
“BMS is committed to improving cancer care by, among other things, addressing scheduling and convenience concerns of patients with a range of dosing options for an immuno-oncology agent that allows for enhanced flexibility,” Fouad Namouni, MD, head of development, Oncology, Bristol-Myers Squibb, said in a statement.
“This positive CHMP opinion reinforces our commitment and we look forward to hearing from the European Commission. Once approved, the Opdivo four-week dosing infused over 60 minutes would enable BMS to deliver on our promise to explore potentially more flexible and convenient dosing options for patients, caregivers and healthcare providers alike.”
Earlier this month, the FDA approved a supplemental biologics license application adding the 4-week dosing schedule for nivolumab across several of the PD-1 inhibitor’s indications.
Physicians can now prescribe the new dosing schedule of 480 mg of nivolumab infused every 30 minutes every 4 weeks for these approved indications:
- Metastatic melanoma (monotherapy or monotherapy phase after combination treatment with ipilimumab [Yervoy])
- Previously treated metastatic NSCLC
- Advanced RCC following prior antiangiogenic therapy
- Previously treated locally advanced or metastatic urothelial carcinoma following disease progression during or after platinum-based chemotherapy
- Classical Hodgkin lymphoma following relapse/progression after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or three or more lines of systemic therapy that includes autologous HSCT
- Recurrent/metastatic HNSCC following platinum-based therapy
- Hepatocellular carcinoma after prior sorafenib therapy
- Adjuvant therapy for patients with completely resected melanoma with lymph node involvement or metastatic disease.
Physicians now have the option of using either the new 4-week dosing schedule or the previously approved schedule of 240 mg every 2 weeks, now available in a new 240 mg vial.
Research presented at the 2017 AACR Annual Meeting indicated that safety and efficacy would be similar between a nivolumab dosing schedule of 480 mg every 4 weeks compared with 3 mg/kg every 2 weeks.2
Using quantitative clinical pharmacology analyses and safety assessments, the investigators examined the predicted risk/benefit profile of the less frequent 480-mg regimen relative to the 3-mg/kg regimen.
Among patients with melanoma, NSCLC, or RCC, there was a <1% difference in the predicted probability of achieving a response. The predicted 1- and 2-year survival probabilities were also similar among patients with these tumor types receiving either of the 2 doses, with differences ranging between 0% to 4.6% at year 1, and 1.9% to 6.9% at year 2.
The FDA first approved nivolumab as a single agent for advanced melanoma in December 2014, as a treatment for patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600–positive, a BRAF inhibitor.
- Bristol-Myers Squibb Receives Positive CHMP Opinion Recommending Approval of Opdivo Four-Week Dosing Schedule for Advanced Melanoma and Previously Treated Renal Cell Carcinoma. Bristol-Myers Squibb. https://bit.ly/2pGtRkQ. Accessed March 26, 2018.
- A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res. 2017;77(13 Suppl): Abstract CT101. doi:10.1158/1538-7445.AM2017-CT101.