Samsung 950 Pro M.2 in an ASUS X99-Deluxe II w/ and i7-5820K and 2 GPUs in x16x8 Crossfire

In section 1.1.5 the manual addresses the expansion slots (pg 1-(7-10)). First we see that for dual GPUs you are suggested to install them in x16/x8 mode in slots 1 and 3. This clearly consumes 24 lanes of the 28 available. For a 40 lane CPU one would use slots 1 and 3 as well but it would operate in x16/x16 mode using 32 of the 40 lanes.

On page 1-9 and 1-10 it address how the SATA Express, U2, and M2 sockets work with the various PCIe slots. Here we see for a 28 lane CPU there is no mention of the M2 socket, but for a 40 lane CPU it is very clear that the M2 socket is shared with PCIe slot 3. In this case, for a 40 lane CPU, the GPUs would operate in x16/x8 mode and the M.2 socket takes 4 PCIe lanes from slot 3. It would seem to me that what happens with a 28 lane CPU is that the M2 slot is disabled when PCIe slot 3 is used. Thus instead of dropping to x8/x8 mode and siphoning 8 lanes from slot 1 to supply the M2 socket, it instead refuses to operate in x16/x4 mode which would enable 4 lanes from slot 3 to be used by the M2 socket. The manual suggests looking at page 1-30 for more information about the M.2 socket, however this page offers no actual help.

Now, the upside. Look back at page 1-8: consider a triple GPU setup. It can offer x8/x8/x8 mode on a 28 lane CPU using slots 1, 3, and 4. What this means is that you'll need to use the Hyper M.2 converter card to install a Samsung 950 Pro as a PCIe card rather than using the native M.2 socket, but if you do this you can install it in slot 4 and have it run in x4 mode along with both GPUs in x8 mode. This should yield an x8/x8/x4 configuration, though you're clearly losing some lanes here. Slots 2 and 5 would operate in PCIe 2.0 mode only on a 28 lane CPU but if all you really need is the dual GPUs and the NVMe SSD plus some SATA devices and maybe some PCIe 2.0 cards, this is a pretty good solution though it's a bit sad that neither U.2 port nor the M.2 socket would be available.

Thing is that manuals say "GPU" when they really just mean any PCIe card. My system for example uses a PCIe 2.0 x8 RAID controller which I'm able to operate at full speed because the motherboard supports SLI. I only have one GPU, but because there are two x8 or x16 cards installed it drops to x8/x8 mode rather than x16/x0. The same should happen here - you put the Hyper M.2 card in the 4th slot and the system thinks it's in a 3-way setup and runs at x8/x8/x4. You probably lose the 4 lanes that would go to the 4th slot in a true 3-way GPU setup (x8/x8/x8) but aside from that, it *should* run.

I'd suggest looking up some reviews as this board is brand new and see if they specifically mention the ability to use M.2 on a 28 lane CPU or not.