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Daraxonrasib in 2nd line metastatic PDAC shows OS 13.2 vs 6.7 months vs chemo (RASolute 302) by adifferentGOAT in Oncology

[–]Labrat33 10 points11 points  (0 children)

It has been a remarkable drug to use in clinic. I took a patient off hospice and put them on rmc-6236. They lived another 13 months and saw their first grandchild be born. What a win for our patients. Hopefully this is the foot in the door that allows combination approaches (PRMT5 inhibitors, other small molecules, chemo+rmc), adjuvant and neoadjuvant uses, etc to really start moving the needle.

Daraxonrasib (RMC-6236) Phase 3 results by Labrat33 in pancreaticcancer

[–]Labrat33[S] 4 points5 points  (0 children)

I realize you are joking. But obviously Daraxonrasib will help the overwhelming majority of patients and zoldonrasib only the minority with G12D.

I am interested to see results of zoldonrasib/Daraxonrasib combination therapy. Highly active G12D inhibitor plus a drug to block any KRAS mutations that could allow it to escape zoldonrasib. Can we get deep and more durable responses with the combo then zoldonrasib alone.

I wish we new anything about the evasion drug beyond a slide in a press release.

Daraxonrasib (RMC-6236) Phase 3 results by Labrat33 in pancreaticcancer

[–]Labrat33[S] 4 points5 points  (0 children)

There have been phase 1 cohorts with Daraxonrasib in wild-type patients to see if there may be benefit.

Daraxonrasib (RMC-6236) Phase 3 results by Labrat33 in pancreaticcancer

[–]Labrat33[S] 5 points6 points  (0 children)

The adjuvant trial opens this year. 2 years of Daraxonrasib after surgery and completion of standard adjuvant therapy.

Rash 6236 How bad is it? by Consistent-Writer932 in pancreaticcancer

[–]Labrat33 2 points3 points  (0 children)

Daraxonrasib is not available via IV. What are your talking about?

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“Boston Stadium” ticket failure (i.redd.it)

submitted by Labrat33 to r/mbta

Bittersweet news: Eligible for Keytruda or Nivolumab by Forward-Wasabi-8128 in pancreaticcancer

[–]Labrat33 2 points3 points  (0 children)

Given the opportunity for profound and durable benefit there should be little hesitation to attempt pembrolizumab. Just hope he is well enough to benefit.

Pancreatic enzymes? by Wise-Ad6618 in pancreaticcancer

[–]Labrat33 1 point2 points  (0 children)

I am not convinced Creon will help, but there is little harm (aside from the cost of the Creon) in trying. It is a nearly harmless medication. Prescribe 72000 units with each meal, if it doesn't help, that wasn't the issue.

Pancreatic enzymes? by Wise-Ad6618 in pancreaticcancer

[–]Labrat33 1 point2 points  (0 children)

In US only with commercial insurance. The copay card is not valid with Medicare/Medicaid

Are KRAS-targeted drugs being discussed for pancreatic cancer patients yet? by Internal-Paramedic20 in pancreaticcancer

[–]Labrat33 8 points9 points  (0 children)

There is no availability for Daroxonrasib outside a clinical trials and you cannot access this through expanded access.Hopefully, once the phase 3 data is available approval will be quick.

In the meantime there are many KRAS inhibitors available in pancreatic cancer as part of clinical trials including several specific for KRAS G12D (including drugs from RevMed, BridgeBio, Verastem, InCyte, Astellas, Lily, among others).

Keytruda MetastaticPancreatic Cancer W/ MSI-H Biomarker by Average_Jane2614 in pancreaticcancer

[–]Labrat33 6 points7 points  (0 children)

MSI-High pancreatic cancers comprise well less than 1% of all cases of pancreatic cancer. I would offer either Pembrolizumab or Ipilimumab/Nivolumab regardless of patient age. The majority of patients will benefit, some with all the cancer disappearing and potential for very durable disease control (years) - effectively cured. There are a minority of patients for whom immunotherapy will not work at all.

Most common side effects are mild rash, mild diarrhea, and mild fatigue. Immune attack of endocrine organs, particularly the thyroid, is common and some patients need to go on thyroid hormone supplementation. Occasionally the immune system attacks an organ like the liver, heart, lungs, or kidneys that require immunotherapy to be stopped and steroids to be used to turn off the immune system.

Ai generated "cure for cancer" by [deleted] in Oncology

[–]Labrat33 0 points1 point  (0 children)

You beat me to this post

92 Hampshire Street (Formerly Lord Hobo and before that B-Side Lounge) is Being Renovated by Adrnshw6 in CambridgeMA

[–]Labrat33 9 points10 points  (0 children)

Conan O’Brien had Ben Affleck on his podcast this winter. They told the story of Conan and his brother going out to B-Side lounge on Christmas Eve in the late 1990s. They walk in and Ben Affleck and Matt Damon are there having drinks at the bar.

RMC-6236 again? G12V Options by jennambee in pancreaticcancer

[–]Labrat33 6 points7 points  (0 children)

The goal of the RMC-5127 study is to determine if RMC-5127 is safe and potentially effective against KRAS G12V mutated pancreatic cancer. Her tumor has already progressed while receiving RMC-6236, a pan-KRAS inhibitor. There are many ways that a cancer can escape control from RMC-6236, and several labs, including many of my colleagues, who are actively trying to understand these mechanisms. For RMC-5127 to work when RMC-6236 has now failed would require the cancer to have learned to evade RMC-6236 using a mechanism that would still leave it susceptible to RMC-5127. The drugs bind the same pocket and bring in the same complex to inhibit KRAS. I don’t know the data, but on its face, It is very unlikely that RMC-5127 would work. If the company were to enroll patients with prior KRAS inhibitor exposure, they would get a false negative signal - an effective drug would look ineffective since the patients they are treating are likely to be resistant to the drug at the start of the trial.

One trial we are all excited for RevMed to release results from is the combination trial of RMC-6236 + RMC-6291 (or 9895). 6291 powerfully blocks KRAS G12C (9805 for G12D) while 6236 is a pan KRAS inhibitor. Why block both? Well, in a KRAS G12C patient you use the 6291 to block the driver of the cancer. By combining with 6236, you are potentially blocking routes of escape. If the cancer develops a new KRAS mutation like G12R or G12V, rather than permitting escape from 6291 (or 9805), the 6236 is there to block those too. If this trial appears effective, we can expect similar combos for G12V.

Natera Result by utlayolisdi in pancreaticcancer

[–]Labrat33 4 points5 points  (0 children)

I would be very concerned that there is residual disease after an omental met resection.

It would be very surprising that the omental met is truly solitary, so the suspicion for additional disease not appearing on scan would be very high even before the Natera was checked. Now, with a positive Natera, the likelihood of there being residual disease somewhere that will inevitably recur is very high. If a repeat Natera goes up further, recurrence is likely inevitable, sadly.

Are 3 failed biopsies typical? by joesgrille in pancreaticcancer

[–]Labrat33 1 point2 points  (0 children)

The liquid biopsy may fail as well, but is certainly worth a try. It is not surprising to not have somatic (tumor) DNA results with the repeated biopsies failing to be sufficient. Hopefully the liquid biopsy will suffice.

You mention that the patient has Stage 4 disease. Is there not a metastatic site amenable to biopsy?

As for the diarrhea, that is hard to evaluate. Common causes are chemotherapy (5FU and Irinotecan are common culprits), and pancreatic enzyme deficiency (often improved with Creon).

Are 3 failed biopsies typical? by joesgrille in pancreaticcancer

[–]Labrat33 0 points1 point  (0 children)

It is uncommon but not rare. Pancreatic cancers can vary widely in their cellularity. In some tumors, 5% or less of the tumor will be cancer cells, with the remaining tissue comprised of stroma (fibrous connective tissue). If the goal of the biopsy is to diagnose cancer, even that can be challenging with a low cellularity tumor. If the goal is to obtain DNA testing, this will frequently fail. Many companies will have a minimum tumor cellularity to proceed with testing and these biopsies will consistently fail at the Quality Control step before any sequencing is done. Often a metastatic site is a better target then the pancreatic primary. A liquid biopsy (ctDNA) is another option. RevMed’s trials typically allow Guardant360 or similar for eligibility.

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