Brad Grey was chairman and chief executive of Paramount Pictures for 12 years, during which he launched major film franchises but suffered losses of nearly half a billion dollars. (Andrew Kelly/Reuters)

Brad Grey, a Hollywood agent who produced television hits such as “The Sopranos” and spent 12 years as head of Paramount Pictures, where he greenlighted such lucrative franchises as “Transformers” and “Star Trek” and resigned in February amid massive losses, died May 14 at his home in Los Angeles. He was 59.

The cause was cancer, his family said in a statement. He stepped down as Paramount’s chairman and chief executive after a year in which the studio reported losses of nearly half a billion dollars.

Mr. Grey, whose career bridged the creative and financial sides of his industry, was long considered a rarity in the film capital: a meticulous, smooth-talking operator who courted actors and comedians, possessed a hitmaker’s taste and was known for his meticulous knowledge of the business world.

“He was the first guy I ever saw in this business who read the Wall Street Journal,” the veteran manager and producer Bernie Brillstein once told Forbes. “I saw him with the paper and said, ‘What are you doing with that ?’ ”

He began his career as an assistant and then a partner with Harvey Weinstein, a onetime concert promoter who went on to form the production company Miramax. The studio was later a crucial collaborator with Paramount, joining with a specialty film division of Mr. Grey’s devising to distribute the Oscar-nominated 2007 films “There Will Be Blood” and “No Country for Old Men.”

Mr. Grey’s “genius at picking and identifying talent was unprecedented,” Weinstein said in a statement Monday.

Born into a family of traveling salesman, Mr. Grey joined with Brillstein in 1984. The duo formed what the New York Times once described as a Hollywood “odd couple” — Brillstein, who died in 2008 and helped shape “Saturday Night Live,” was a flashy and voluble presence alongside the spare and laconic Mr. Grey — while building one of Hollywood’s most powerful management firms.

Their clients included televisions stars (Jennifer Aniston and Courtney Cox), comedians (Garry Shandling and Mike Myers), actors (Brad Pitt and Nicholas Cage) and former politicians such as New York Mayor Rudolph W. Giuliani, for whom Mr. Grey negotiated a $3 million book contract.

Crucially, in 1994 Brillstein-Grey Management also began producing films and television shows — many of them featuring some of the 200-odd stars that the firm represented.

It was, Mr. Grey acknowledged, a clear conflict of interest: managers negotiating contracts for their stars while also haggling on behalf of the programs they appeared in. “I don’t shy away from it,” he told Forbes magazine in 2002. “I like to be crystal clear about it and acknowledge it.”

The practice resulted in at least one lawsuit. In 1998, Shandling sued Mr. Grey for $100 million, alleging that the manager and producer had misused their business relationship to gain an unfair advantage for himself and for other clients. The case was settled out of court.

Mr. Grey’s strategy, which Shandling likened to “double dipping,” helped him reap millions of dollars from hits such as the NBC sitcom “Just Shoot Me” and the HBO crime drama “The Sopranos,” for which he served as co-executive producer.

“Sopranos” creator David Chase credited Mr. Grey with finding a home for the series after it was rejected by the broadcast networks, and told GQ magazine in 2005 that Mr. Grey’s blue-collar background made him a crucial collaborator behind the scenes. “Whatever he responds to I usually go with,” Chase said, “because he responds to the humanity of the stories.”

The show won Emmy Awards for outstanding drama series, in 2004 and 2007, and marked a turn toward increasingly ambitious productions for Mr. Grey. He joined Pitt and Aniston’s production company Plan B as a partner, and there — partly inspired by his two young sons — produced the Johnny Depp film “Charlie and the Chocolate Factory” (2005) and Martin Scorsese’s mobster drama “The Departed” (2006).

Mr. Grey had by then taken the reins of Paramount, with the approval of the parent company Viacom led by Sumner Redstone. Mr. Grey was charged with reversing a slump that began under his predecessor, Sherry Lansing.

He eliminated about a third of the company’s 3,000 employees and brought in fresh talent, partnering for several years with Steven Spielberg and the production company DreamWorks SKG, while also scoring first-look deals with blockbuster producers J.J. Abrams and Michael Bay.

In 2007, two years after Mr. Grey took over, the studio topped the U.S. box office charts with $1.5 billion in domestic revenue. Paramount scored hits with the franchises “Transformers,” “Star Trek” and “Mission: Impossible.” By 2012, Vanity Fair reported, Mr. Grey had produced eight of Paramount’s 10 highest-grossing films.

Yet declining movie-theater attendance and a succession of box-office bombs — among them “Teenage Mutant Ninja Turtles: Out of the Shadows” and “Zoolander 2” — caused Paramount to sink into the red. In its most recent fiscal year, the studio reported losses of $445 million.

Mr. Grey was optimistic about engineering a turnaround. “The history of show business,” he told Vanity Fair in October, “is that you’re always a couple of hits away from a turnaround.”

Four months later, with Viacom under new chief executive Bob Bakish, Mr. Grey resigned.

Bradley Alan Grey was born in the Bronx on Dec. 29, 1957, and grew up in Spring Valley, N.Y. His grandfather sold buckles in New York’s garment district, and his father sold women’s handbags to stores in the South.

Mr. Grey studied communication and business at the State University of New York at Buffalo. After graduating in 1979, he teamed with Weinstein, a fellow Buffalo alum.

His first marriage, to Jill Gutterson, ended in divorce. Survivors include his wife of six years, Cassandra Huysentruyt Grey, who runs the luxury beauty line Violet Grey; three children from his first marriage; a son from his second marriage; his mother; a brother; and a sister.

Mr. Grey liked to say that the nature of the business was to oscillate between success and failure. Last year, when Paramount reported gigantic financial losses, the studio also snagged Best Picture nominations with the science-fiction film “Arrival” and the August Wilson adaptation “Fences.”

“We fail more than we succeed in show business,” Mr. Grey told Forbes, “but every now and then we really succeed.”