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The phrase "a major setback in" is correct and usable in written English.
It can be used to describe a significant obstacle or difficulty encountered in a process, project, or situation.
Example: "The unexpected loss of funding was a major setback in the development of the new software."
Alternatives: "a significant obstacle in" or "a considerable hindrance to".
Exact(57)
Recent blows included a major setback in a workers' compensation insurance arrangement that went sour.
This has been described as a major setback in efforts to tackle the disease.
In January 2008, Dr. Benhamou told Mr. Skowron of a major setback in the trial before the information became public.
Bath suffered a major setback in the 17th minute when Lipman was felled after an accidental collision.
Donald Trump suffered a major setback in Iowa overnight, as the Republican hopeful came second in the first caucus to Texas junior senator Ted Cruz.
He said the paper's closure "would be a major setback in the development of the free press in Belarus and a great loss for Belarussian society".
Several officials said Mr. Karzai's release of Mr. Dastagir was a major setback in the struggle to roll back the Taliban presence in Badghis.
Chris Hughton refused to view this draw as a major setback in Norwich's quest to distance themselves from the Premier League relegation fight.
She stayed but suffered a major setback in the fourth game of her sophomore season, when she tore the anterior cruciate ligament in her left knee.
Anti-slavery groups are mounting a spirited effort to have the register reinstated, as its demise would be a major setback in the fight against slavery.
The revolt by Mr. Misuari represented a major setback in what had once seemed an important step toward bringing the often rebellious Muslim minority into the national framework.
More suggestions(16)
a substantial setback in
a major obstacle in
a major impediment in
a major reversal in
a major failure in
a major defeat in
a tremendous setback in
a considerable setback in
a major backlash in
a major blow in
a major disappointment in
a major drawback in
a major relapse in
a major inconvenience in
a major lapse in
a major event in
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Since I tried Ludwig back in 2017, I have been constantly using it in both editing and translation. Ever since, I suggest it to my translators at ProSciEditing.

Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com