BEIRUT (AFP) - Islamic State in Iraq and Syria (ISIS) militants clashed on Saturday (July 23) with US-backed fighters in the Syrian town of Manbij, pursuing their fierce defence of the militant stronghold and ignoring a deadline to leave.

There are growing fears for the fate of civilians trapped in Manbij, formerly a key stop along ISIS' supply route from neighbouring Turkey into its self-styled Islamic "caliphate" in Syria.

The US-backed Syrian Democratic Forces (SDF) penetrated the town one month ago but have since been hindered by a bloody ISIS counter-offensive amid concerns about civilians.

On Saturday, ISIS militants appeared to ignore a 48-hour ultimatum to leave issued by the Manbij Military Council, a key SDF member.

"The 48-hour period is over, and there will be no more opportunities like this one for Daesh (ISIS)," a commander from the council told AFP on condition of anonymity.

ISIS has "not responded" to the SDF's offer and instead "attacked our positions", he said.

The ultimatum came after at least 56 civilians, including children, were reportedly killed on Tuesday in US-led coalition air strikes near Manbij.

The commander pledged that his forces would "intensify our attacks on their remaining positions".

The council's spokesman, Sherfan Darwish, stressed in an online statement Saturday that SDF forces in Manbij "are committed to securing safe passage to the best of their ability for any civilian able to flee Daesh's brutality".

Thousands of civilians have already fled Manbij, which is in Syria's northern Aleppo province.

More than half of Syria's population has been displaced since the conflict erupted in 2011, and at least 280,000 people have been killed.

The Syrian Observatory for Human Rights said SDF forces were advancing in Manbij, moving steadily north from districts they already control in the west and south.

An SDF field commander inside Manbij told AFP on Saturday that the main clashes were "near the security quarter in the centre of the town".

The civilian deaths in Tuesday's raids sparked an intense backlash from activists and rights groups, and a call from a prominent Syrian opposition body for the coalition to halt its air campaign until a thorough investigation is completed.

The coalition has said it is investigating the reports of civilian fatalities in the town of Al-Tukhar, 14km from Manbij.

Bombing raids have, meanwhile, continued unabated, with the Pentagon reporting nine strikes near Manbij on Friday.

Coalition spokesman Chris Garver said Friday that ISIS was mounting an exceptionally tough fightback.

The battle has intensified as SDF units move deeper into the town, he said, "which is sort of different than what we saw in Ramadi and what we saw in Fallujah", two Iraqi cities from which militants were ousted this year.

"It's a fight like we haven't seen before." Garver estimated that the SDF had seized roughly half the town, an area still housing at least 2,000 civilians.

ISIS was using residents "as human shields and as bait" in order to draw SDF fire towards civilians, Garver added.

Observatory head Rami Abdel Rahman accused ISIS of "pushing children towards the frontlines" as it tried to defend its positions.

Garver said Tuesday's controversial air raid was called after the SDF "observed a large group of Daesh fighters in a convoy who appeared to be readying for a counterattack".

The coalition later received reports that there may have been civilians mixed in among the militants, he added.

Earlier this year, the coalition said 41 civilians had been killed in its bombing raids in both Iraq and Syria since August 2014.

But the Britain-based Observatory says that 594 civilians have been killed in coalition raids across Syria - more than 100 in Manbij alone.

ISIS and its militant rival Al-Nusra Front are not included in global efforts to end the fighting in war-ravaged Syria.

Repeated attempts by Washington and steadfast regime ally Moscow to reinforce a nationwide ceasefire have largely failed, with violence continuing.

Dozens of civilians died in bombardment Saturday, the Observatory said, with 10 killed in raids by unidentified warplanes in the eastern province of Deir Ezzor and eight dead in suspected Russian strikes in the north-west.

Air raids killed seven family members, including four children, in the central Hama province, and another eight people including three children east of Damascus, it said.

The besieged parts of northern Aleppo city were also pounded including with barrel bombs, killing 12 civilians in several neighbourhoods.