Nivolumab Granted Accelerated Approval By The FDA

Nivolumab Granted Accelerated Approval By The FDA

shutterstock_180415025The U. S. Food and Drug Administration (FDA) recently granted accelerated approval to nivolumab (commercialized as OPDIVO by the Bristol-Myers Squibb Company) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

Nivolumab (OPDIVO) is a human programmed death receptor-1 (PD-1) blocking antibody, that upon binding with the checkpoint receptor PD-1 expressed on activated cancer cells, inhibits the capacity of tumor cells to evade the immune system, allowing for an effective immunological anti-tumoral response.

Effectiveness of nivolumab was confirmed based on the overall response rate (ORR) and response duration of 120 patients from a continuing open label randomised clinical trial of 370 patients with unresectable or metastatic melanoma, after a 6 month follow-up of a 3mg/kg nivolumab dose given intravenously every 2 weeks or chemotherapy (in the form of dacarbazine or in the form of combined carboplatin and paclitaxel). Treatment was given until disease progression or observed toxicity.

Of these 120 patients, 58% and 42% had ECOG performance status measured at baseline of 0 or 1, respectively. Disease features included BRAF V600 mutation -positive melanoma (22%), elevated lactate dehydrogenase (56%), M1c disease (76%), history of brain metastases (18%), and two or more preceding treatments for advanced or metastatic disease (68%).

Results from the trial revealed that the ORR was 32%, with four complete responses and 34 partial responses. Five responding patients have progressed, while the remaining 33 patients (87%) have ongoing responses (range 2.6+ to 10+ months).  Thirteen patients have ongoing responses of 6 months or longer.

Most common side effects (>20%) seen in 2% to less than 5% of the 268 patients receiving nivolumab included abdominal pain, hyponatremia, augmented aspartate aminotransferase, and increased lipase.  Immune-mediated unfavourable responses included pneumonitis, colitis, hepatitis, nephritis/renal dysfunction, hypothyroidism, and hyperthyroidism.

Despite the encouraging results, the FDA still requires Bristol-Myers Squibb to conduct a multicenter randomized controlled trial/trials to evaluate nivolumab upon comparison with other compounds, as a leading effective therapy for patients with unresectable or metastatic melanoma.

Nonetheless, based on preliminary results of its clinical feasibility in this group of patients, nivolumad was granted breakthrough therapy from the FDA last September.

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