WASHINGTON — In a searing denouncement, President Barack Obama castigated Donald Trump as “unfit” and “woefully unprepared” to serve in the White House. He challenged Republicans to withdraw their support for their party’s nominee, declaring “There has to come a point at which you say ‘enough.’”

While Obama has long been critical of Trump, his blistering condemnation Tuesday was a notable escalation of his involvement in the presidential race. Obama questioned whether Trump would “observe basic decency” as president, argued he lacks elementary knowledge about domestic and international affairs, and condemned his disparagement of an American Muslim couple whose son was killed while serving the U.S. Army in Iraq.

A chorus of Republicans has disavowed Trump’s criticism of Khizr and Ghazala Khan and the Republican nominee’s calls to temporarily ban Muslims from coming to the U.S. But Obama argued that isn’t enough.

“If you are repeatedly having to say, in very strong terms, that what he has said is unacceptable, why are you still endorsing him?” Obama asked during a White House news conference. “What does this say about your party that this is your standard-bearer?” No prominent Republican responded to Obama’s challenge.

Instead, it was Trump stunningly withholding his support from top GOP lawmakers, including House Speaker Paul Ryan. In an affront to his party’s top elected official, Trump told The Washington Post he wasn’t “quite there yet” on an endorsement for Ryan in his primary next week.Ryan’s campaign said, “Neither Speaker Ryan nor anyone on his team has ever asked for Donald Trump’s endorsement. And we are confident in a victory next week regardless.”

Trump also said he was not supporting Sen. John McCain of Arizona in his primary, and he dismissed Sen. Kelly Ayotte as a weak and disloyal leader in New Hampshire

Democratic nominee Hillary Clinton sees those GOP concerns about Trump as an opportunity to reach out to party moderates — particularly women — who may be so upset by the nominee that they’re willing to look past policy differences and questions about Clinton’s character.

Obama — who is enjoying heightened popularity in his eighth and final year in office — plans to campaign robustly for Clinton through Election Day. He and first lady Michelle Obama spoke at last week’s Democratic convention in Philadelphia.

The Khans also appeared at the convention, with Khizr Khan telling the story of his son, U.S. Army Capt. Humayun Khan, who was posthumously awarded a Bronze Star and Purple Heart after his death in 2004. Khan criticized Trump’s position on Muslims and asked whether the real estate mogul had read the Constitution.

For most politicians, tangling with a bereaved military family would be out of bounds. But Trump dove in, questioning why Ghazala Khan did not speak, implying her religion prevented her from doing so, and saying he was “viciously attacked” by Khizr Khan.

Trump’s criticism was part of a familiar pattern: He can’t let go of a perceived slight, no matter the potential damage.

Trump’s unwillingness to let the Khan matter subside sparked outrage from several Republicans.

Sen. John McCain, an Arizona Republican and former prisoner of war, said Trump did not have “unfettered license to defame those who are the best among us.” Rep. Mike Coffman, a vulnerable Republican in a competitive Colorado district, said he was “deeply offended when Donald Trump fails to honor the sacrifices of all of our brave soldiers who were lost in that war.” Missouri Sen. Roy Blunt said the Khans “deserve to be heard and respected.”

Obama argued those denunciations “ring hollow” as long as Republicans continue to back Trump in the White House race.

Trump’s response? On Twitter, he said, “President Obama will go down as perhaps one of the worst president in the history of the United States!”

Sen. Mark Kirk, who is facing a tough re-election fight in Illinois, rescinded his endorsement of Trump in June after the GOP nominee criticized an American-born judge’s Mexican heritage.

Others, including Senate Majority Leader Mitch McConnell and Ryan, have broken with the nominee on individual issues but continue to back his candidacy.

• Associated Press writers Erica Werner and Jonathan Lemire contributed to this report.