I have noticed that my 4K movies will buffer very often if the overall bitrate is over 40 Mbps, so I have been reencoding them using Handbrake and I had used my own preset based on some trial and error. Also note: BACKUP YOUR ORIGINAL FILES. 
Summary Tab
Format: .mkv
Dimensions Tab
Cropping: Automatic (although on some of my movies it didn’t cut the top and bottom bars off the movie and I had to adjust this to 264-280 top and 264-280 bottom)
Anamorphic: Automatic
Modulus: 2
Filters Tab
Everything off except Deinterlace, which is set to Decomb/Default/Default
Video Tab
This is where I had made most of my tweaks.
- Video Codec: H.265 10-bit
- Framerate: Same as source, Peak Framerate
- Quality: Constant Quality, RF18 (you will have to play with the RF because you can also move it to 20 to save on space and not lose much quailty)
- Optimise Video:
- Encoder Preset: Fast
- Encoder Tune: None
- Encoder Profile: Main 10
- Extra Options: strong-intra-smoothing=0:rect=0:level-idc=5.1:hdr:hdr-opt:chromaloc=2
Audio Tab
You can add any of them you want, but to set your “standard”, I would suggest clicking on “Selection Behavior” and then making the modifications there.
Selection Behavior Screen:
- Track Selection Behaviour: All Matching Selected Languages
- For Additional Tracks: Use All Tracks as Templates
- Choose Language: English
- Auto Passthru Behavior: all checked
- Fallback Encoder: AC3
Automatically Add Tracks
- Codec: Auto Passthru
- Codec: AAC (avcodec), Bitrate, 384, mixdown: 5.1 channels, Samplerate 48, DRC 0, Gain 0
- Save
And then for each “English” audio track, it would add the Auto Passthru and a mixdown of 5.1. For stereo tracks, it automatically changes the setting from 5.1 channels to either Dolby Surround or Stereo.
Subtitles Tab
this one is a bit tricky, because sometimes you have to run your files through Subtitle Edit and/or MKVToolNix to fix up or add good subtitles. Once they’re in place, I always set my “Selection Behavior” to the following:
- Track Selection Behavior: All Matching Selected Languages
- Burn-In Behavior: Foreign Audio Track
- uncheck Add Closed Captions when available
- check Add Foreign Audio Scan
- Choose Language: English
- Save
With these files being very large, I choose to burn in the foreign audio subtitles so Plex doesn’t have to waste processor transcoding the subtitle track. As always, you’ll have to check to make sure your foreign audio scan is working properly and actually burning in the correct subtitles. 
Chapters Tab
I usually leave this one to defaults.
I named my Custom Preset “HDR h265 v1”
After running my ginormous 4K movies through these encoding settings, the file size is normally cut in half and the overall bitrate is reduced to something under 30Mbps. For instance one of my movies went from 64Mbps to 19Mbps Overall Bitrate, file size from 58GB to 17GB. However, it’s still 2160p and HDR, and it now plays on my Plex Server to my Roku 4K without buffering or stalling.
Not sure if this was what you were looking for, but this is how I used Handbrake to fix my buffering issue. I am now going through each of my 4K movies and running 8-10 in a batch at a time. Gonna take a while but it does a pretty good job running in the background.
Plex Server: MSI Z370 Gaming Pro Carbon; Intel Core i7-8700k; 16GB DDR4 3600Mhz; Win10 Pro; MSI GTX 1060 Aero ITX 6G OC; Intel Pro/1000 PT Dual Port Server Adapter