FDA Approves 4-Week Dosing Schedule for Nivolumab

The FDA has approved a supplemental biologics license application to add a 4-week dosing schedule for nivolumab (Opdivo) across several of the PD-1 inhibitor’s indications. The new dosing schedule allows 480 mg of nivolumab to be infused over 30 minutes every 4 weeks for these approved indications:

• Metastatic melanoma (monotherapy or monotherapy phase after combination treatment with ipilimumab [Yervoy])
• Previously treated metastatic non—small cell lung cancer (NSCLC)
• Advanced renal cell carcinoma (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 squamous cell carcinoma of the head and neck 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, according to Bristol-Myers Squibb, the manufacturer of nivolumab.

“We continuously learn new ways to individualize treatment with immuno-oncology therapies, and in my experience, what works for one patient may not be optimal for another,” Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center at NYU Langone Health and professor of medicine at NYU School of Medicine, said in a statement.

“For instance, some patients may need the support of 2-week visits with their healthcare team, while for others, a 4-week interval may be more appropriate and better suited to their treatment needs. With this approval, we now have additional ways to help tailor patient care,” added Weber.

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. 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.

“At Bristol-Myers Squibb, we are united in our mission to fight cancer from all angles and recognize every patient has unique needs. From the introduction of our first Immuno-Oncology agent through today’s approval of flexible dosing options at two- or four-week intervals, we are relentless in pursuing innovative options for the cancer community,” Johanna Mercier, head, US Commercial, Bristol-Myers Squibb, said in a press release.

“With this approval, we now offer the most robust range of dosing options for an Immuno-Oncology medicine, providing enhanced flexibility to help address each patient’s specific needs,” added Mercier.

Reference

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.