Bristol-Myers said it received a so-called complete response letter from the health regulator, which indicated the need for additional data in the BRAF mutated patient population.
The regulator issues a complete response letter when a new or generic treatment cannot be approved in its current form.
The FDA approved Opdivo as a single agent for the treatment of patients with BRAF V600 wild-type melanoma earlier this week, but on Friday declined the approval of the drug for treating BRAF V600 mutation positive metastatic melanoma.
Opdivo, first approved in December 2014, raked in worldwide revenue of $467 million in the nine months ended Sept. 30.
The drug has been approved for five other indications in the past 12 months.
Metastatic melanoma is the least common skin cancer. It is also the most deadly because it spreads (metastasizes) quickly and easily to other parts of the body.