@bradthompson88 , @wpprescott would not be able to do any other SOC cancer treatment simultaneously with trial drugs. The trials are super-regulated to make sure only the trial drug itself is or is not contributing to the patient's response. They also want to know about and approve/reject any complementary or alternative meds (herbs, OTC, etc) you take on a regular basis so they can rule out their impact on trial drug response as well.

@wpprescott , I'm sorry to hear about your dilemma, but it sounds like you do have options. I also have the KRAS G12D mutation. I had the option to start on a pan-RAS trial drug a month ago, but it was too much travel, and I lost my slot while weighing my options. The same trial (and another similar one) was supposed to open up closer to home, but they have not materialized. 🙁

Among the "RAS" related mutations, there are NRAS and KRAS families, and then specific variants (like G12D) within them. The "pan-RAS" drugs (like RMC-6236) target the whole family, sort of like a shotgun, but may have more side effects because of the wide targeting. The more variant-specific drugs (like RMC-9805) are said to have fewer side effects because of their more precise targeting. Both types are getting relatively good reviews so far, but both are still so early in development that it's hard to say how effective or long-lasting they will be.

In my case, I also have a germline ATM mutation. In asking around, 5 different oncologists have emphasized to me how a KRAS mutation is the driver in so many pancreatic cancers that it's the best thing to target first if you have a choice.

MSK offered me one trial that didn't target either of my mutations, so I passed on that one. If they can get you into a pan-RAS or KRAS G12D trial that close to home, it sounds like the ideal choice.

My pre-Whipple response to Folfirinox was pretty ho-hum. After my post-Whipple recurrence, I started Gemcitabine + Abraxane + Cisplatin. Everyone is different, but I got a much more robust response (in terms of CA19-9 and MRI) to it than Folfirinox, with far fewer treatment side effects. I got about 15 months of good control from it before drug resistance started to develop.

So, until I get into the right trial, the same 5 oncologists mentioned above have also recommended I try the one SoC drug I haven't already tried: Onyvide (nano-liposomal irinotecan, aka Naliri).

Although I had "regular" irinotecan as part of my Folfirinox, the Naliri formulation is supposed to penetrate tumors better. I will get it with Leucovorin and 5-FU (ingredients also in Folfirinox), but without the Oxaliplatin. The thought process is that after so long on Cisplatin, I might be drug-resistant to platins in general, and skipping the Oxaliplatin will give me time to recover from all the Abraxane-induced peripheral neuropathy.

Those are basically all the options on the table I know of, unless you have other targetable mutations or an oncologist willing to go outside the box and try another drug off-label. There's a lot of research and $$$ going into RAS-related trials right now, so that seems like a good place to focus your trial search.

As an aside, there are other targetable properties of cancers that aren't necessarily gene mutations. Cancer cells may express certain proteins that can be recognized by certain "antibodies" which would carry a cytotoxic payload to the cancer cells. CLDN18.2, TROP2, and Mesothelin are three that I'm aware of. Sometimes the payload is standard chemo drug (making it an ADC -- Antibody/Drug Conjugate), or it could be a "cellular therapy" where living immune cells do the killing.

There's a newer trial going on at MD Anderson going on right now, in which CAR-NK (Natural Killer) cells engineered to recognize TROP2 are injected by IV. It's attractive (one shot and done), but I don't qualify because of the similar trial/treatment I did last year (the same cells, but injected into my peritoneal space rather than intravenously. It's hard to tell whether they work better as an IV than in peritoneum, but failure of the latter is why I'm still a mess today. That's always a risk with trials...

Wishing you the best with your decision and treatment!

--mm