"Me and Earl and the Dying Girl" is a smart film about thoughtful teenage characters who have far more on their minds than who they are taking to prom (although that's also on some of their minds, too). A sensation at the 2015 Sundance Film Festival—it won both the Grand Jury Prize and the Audience Award—the picture inadvertently invites comparison to 2014's similar "The Fault in Our Stars," but is different enough in style and sensibility to stand on its own without coming off as a familiar redux. Director Alfonso Gomez-Rejon (2014's "The Town That Dreaded Sundown") and screenwriter Jesse Andrews (adapting his own 2012 novel) bring welcome scope and culture to a slyly humored drama about an unlikely friendship between two high school seniors moving toward very different fates as they approach graduation. There are hints of undisputable inspiration in Gomez-Rejon's approach—Wes Anderson's "Rushmore" and Alexander Payne's "Election" come immediately to mind while watching—but the filmmaker uses them merely as a jumping-off point for his own uniquely perceptive viewpoint.

Greg Gaines (Thomas Mann) is a die-hard cinephile and aspiring director whose 42 home-made films (most of them affectionate movie spoofs) adorn his family's living-room shelves. At his Pittsburgh high school, his goal is to blend in rather than be noticed. At lunch, he typically heads to the office of history teacher Mr. McCarthy (Jon Bernthal) to watch classic cinema alongside his sort-of friend/kind-of co-worker Earl Jackson (RJ Cyler). When Greg's mom (Connie Britton) learns that his classmate, Rachel Kushner (Olivia Cooke), has been diagnosed with acute myelogenous leukemia, she urges him to reach out to her. Greg barely knows Rachel, and when he drops by her house she, in turn, makes it clear that she is not interested in being his charity case. Nevertheless, the more they hang out, the more they bond with each other. This isn't like the movies, though, Greg informs us, and there will be no passionate declarations of love or riding off into the sunset. Rachel doesn't die, either, he adds reassuringly, but as Rachel grows sicker and Greg neglects his schoolwork to secretly complete an original film dedicated to her, hope for their respective futures starts to gradually dim.

"Me and Earl and the Dying Girl" sounds on paper like a downer, and there are certainly heavy topics at play, but a straightforward synopsis cannot do justice to the wit and exuberance with which Gomez-Rejon and Andrews tackle the subject matter. Greg, who narrates, treats his own story like a movie, verbally breaking the fourth wall to speak to an audience whom he is sure has begun to second-guess the story's potential maudlin trappings. Greg and Rachel are reserved and even contentious at first—he has been all but forced by his mom to contact her, and she isn't sure she should get close to anyone as she faces a tough battle ahead—but they become warmer as they discover they genuinely like each other. That they never can quite say out loud what they mean to each other is both painfully accurate and a little disappointing for viewers who are accustomed to more overt onscreen gestures. If there is an unfinished quality to this pair and their time together, that is in keeping with Rachel's confrontation with her own piercingly delicate mortality. Still, it wouldn't have hurt to include one or two additional scenes with them to more fully flesh out the impact of their relationship.

Thomas Mann (2015's "Welcome to Me") is a revelation as Greg, the earnest eyes and ears of the picture. Prone to being irresponsible and unreliable as he floats through his final gasps of high school—his choice to drop the ball on all tests and assignments is frustrating, to say the least—Greg ultimately balances out his errors in judgment with his big heart and creative ambition. Olivia Cooke (2014's "Ouija") brings a heartaching dignity to Rachel even in moments when she threatens to give up her fight. Kids Rachel's age are normally in the thrall of saying good-bye to childhood and hello to a horizon involving higher education and newfound independence, but she doesn't have that luxury. Her alternate bitterness, strength and sense of hopelessness all ring true. Likewise, Greg has never before been close to anyone who has been so ill, and the steps he takes to navigate this tricky terrain hold an honest pang. Mann and Cooke work exceedingly well together even when few words are being spoken.

In an unassumingly confident screen debut, RJ Cyler portrays Greg's somewhat enigmatic confidante Earl, a young man who is faithful to a fault but far from a pushover. Despite being prominently featured in the title, Earl is an admitted afterthought next to his two fellow lead protagonists. In smaller but affecting turns, Molly Shannon (2014's "Life After Beth") is both funny and vulnerable as Rachel's single mother, Denise, casually self-medicating as she confronts losing her only child, while Katherine C. Hughes (2014's "Men, Women & Children") is spirited and vivacious as Rachel's friend, Madison, revealing appreciable shades that allow her to grow beyond a pretty archetype.

Cleverly buoyant before hitting a number of genuinely poignant notes, "Me and Earl and the Dying Girl" is respectful and understanding of teenage behavior and the struggles life can throw no matter one's age. Andrews' writing is cunning and tonally controlled, never overstepping into farce and only approaching melodrama when it is earned. The script isn't airtight, however, as in an early scene where Greg seeks out Mr. McCarthy to ask him if he knows anything about leukemia. Why the savvy, free-thinking Greg wouldn't just take the initiative to research the disease on the Internet is never answered. As for the story's final beats, they conceptually come together, but are the one section where it seems as if Garcia-Rejon gets lost, searching for the proper way to close out the picture. Minor nitpicks aside, this is an inspired coming-of-age entry, meticulously lensed by cinematographer Chung-hoon Chung (2013's "Stoker"). To have an adolescent protagonist in a picture set in the twenty-first century who is passionate and well-educated in cinema history may be a clever way to pander to a specific brand of upscale audience, but there will be no complaints on this front. Best-case scenario, "Me and Earl and the Dying Girl" might serve to expand the horizons of younger viewers who do not quite grasp its amusing wave of film references. Enthusiasts of The Criterion Collection will be in heaven.