Are you currently (or have you been) in a Clinical Trial?
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A couple of exciting new papers!
1) A new Nature paper identifies a gene, DDR1, that acts in TNBC to protect the cancer cells from the immune system. Knockdown or inactivation of DDR1, or a DDR1-specific monoclonal antibody developed by the authors, greatly increases killing of TNBC by T cells.
https://www.sciencedaily.com/releases/2021/11/2111...
this paper extends earlier findings that show that DDR1 is over-expressed in many breast cancers, not just TNBC, and that inhibition of anti-DDR1 antibodies increase T cell infiltration and response to checkpoint immunotherapy.
https://www.spandidos-publications.com/10.3892/or....
https://pubmed.ncbi.nlm.nih.gov/30801016/
*It is interesting to consider that cancers which have mutated from ER-positive to ER-negative become much more accessible to killing by the immune system, and the reason is unknown. Perhaps these cells have mutated or lost expression of DDR1?
2) In unrelated work, another group found that PI3KCA-mutant ER-positive breast cancers can be effectively treated with CDK4,6 inhibitors if they are used in combination with a DDR1 inhibitor.
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A few days ago, the biotech Parthenon, who are collaborators of the authors of the Nature paper described above, announced they have raised 65M funding to pursue the development of PRTH-101, a DDR1 inhibitor. They say DDR1 forms a "barbed-wire-like" structure around breast and other cancers, protecting them from immune system attack, so the goal is to disable this physical barrier to enable T cells to get in...
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Is it just me??? I have been doing research about PARP inhibitors for TNBC and I see 2 available..HOWEVER, from what I "think" I am understanding is that our MO's can only prescribe this IF we have the BRACA GENE!!!!! So really in order to get a PARP inhibitor if we don't have that gene (I don't) and are TN we need to get into a trial ... is this correct? Cross Posting
ALSO regarding the MEM trial...if they are injecting the tumors directly how does that work with bone mets???
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FOR THOSE INTERESTED IN PARP INHIBITORS INFO (LIKE I WAS) i got a GREAT easy to read explination in a FB group...
PARP inhibitors are targeted therapy for BRCA1/2 mutated patients. BRCA can be a germline (hereditary) DNA mutation, or it can be somatic (acquired), which means it's not in a person's DNA, it's only found in the DNA of the cancer cells. The reason for not using PARP inhibitors for those who are BRCA-negative is because it if the DNA damage repair gene (BRCA) is functioning properly, the targeted therapy would likely not work for that person. In other words, there's no need to repair something that isn't broken (BRCA works properly, not mutated). I know this is a long explanation. So, if you do not have a BRCA mutation (germline or somatic), exposing you to a PARP inhibitor would likely not stop your cancer from growing/spreading. It would be a treatment failure that potentially allows your cancer to progress.Using an everyday repair analogy - if your car stopped running because the motor was broken, replacing your tires wouldn't "fix" the broken motor. Even if your tires aren't in good shape, replacing them won't get the motor running. Using a PARP inhibitor for someone who doesn't have a "broken" DNA repair gene (BRCA 1/2) would likely not kill their cancer, because BRCA mutation is not what's fueling the growth, or allowing the cancer cells to continue living.Dana Farber does these cute little science videos, this one explains how PARP inhibitors work. The video is embedded in this article: https://blog.dana-farber.org/.../how-do-parp-inhibitors.../
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Nicole, that is generally correct, but BRCA is not the only DNA repair gene out there, so you don’t have to have a BRCA mutation to be potentially sensitive to PARP inhibitors. CHEK2 mutations are believed to be similar to BRCA mutations with respect to PARP inhibitors, and Lynparza (olaparib) is already approved for CHEK2 mutant prostate cancer. Not yet approved for breast, but there is a trial for the newer, better PARPi talazoparib open to CHEK2 mutant breast cancer NCT02401347: TalazoparibBeyond BRCA (TBB) Trial.
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Piggy thanks..too bad that trial is only in CA....
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After waiting 10 days, the CERAN study disqualified me again for the IVIG. Said I have to be off a year. I’m at 6 months.
Dr Hamilton did not give a plan B or C to the trial intake nurse and she is in clinic today. So I have to wait.
Anyone here know about serd Zn-c5? https://clinicaltrials.gov/ct2/show/NCT03560531#contacts
My MDACC MO said she would check for their trials, but I don’t trust her to move quickly so I am taking the bull by the horns and calling my MDACC phase 1 trial doc myself. MO said next standard of care would be halaven, but I did not respond to previous chemo at all. She also mentioned trying tamoxifen but I avoided that due to potential blood clots.
I can try to get the neuroendocrine treatment back on track. Or hopefully find a different targeted therapy.
Feeling anxious.
Dee
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Dee you are so informed and on the ball..gosh I feel so inadequate.....anyway I don't remember if you said but I am assuming with new biopsy your cancer is still neuroendocrine?
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AlabamaDee,
I am in a similar place to you and doing everything I can to try to calm the anxiety: yoga, dance, acupuncture, qi gong, massage, seeing a regular talk therapist and a specialized onco psychologist. I also started taking a low dose of 7.5 mgs of Remeron, an anti-depressant. I take Gabapentin and cough syrup with Codeine for my persistent cough at night. All three meds have helped me to sleep which makes a big difference. I feel that I have made a lot of progress in trying to stay positive despite the very scary prospects. But I can't completely get rid of the anxiety all of the time.
I am on Halaven now. It is very tolerable but I know it is the last-resort FDA-approved treatment. I have high hopes to get on the ARX-788 trial at USC. My MO is working on it.
My biggest bright light is that my bloodwork and vitals continue to be good despite my progression, weakness, and shortness of breath. I believe that my body can perform miracles if I give it the proper love and care. I was recently introduced to an amazing acupuncturist who restricted my diet: no dairy, no red chili, no sweets, no fried or greasy food, no alcohol, tea, or coffee. Altogether, I have a top-notch team of alternative and Western medicine practitioners. I will do what I need to do to give my body the support it needs. I am also lucky to have the incredible support of friends and family.
I am grateful to have lived this long with the extensive list of mets I had at my original Stage IV diagnosis. And that for most of these 7+ years I have had a high quality of life. I am grateful that I'm mobile and not in pain. But I want more. I want to be here to support my husband and kids. I want to be here because I love my life.
I hope that you and I and the other wonderful and kind people on this board live long enough to see new and better treatments, perhaps even a cure.
Big hugs, Susan
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Nicole- yes it is still neuroendocrine.
Susan- your story and encouragement are beautiful words.
Dee
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Beautiful thoughts Susan. I too see "last resort chemo" looming in the distance but I have been blessed with feeling okay and being able to extend life as long as I have. I sing with 2 sweet Adeline choruses and keep up my energy and focus that way. I ask Alexa to play dance music to make me start moving in the morning. I Hope to get a new dog soon to keep me walking, an 8 year old rescue, mine passed a away in Sept. Hugs, Nina
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For the trial Dee was on, ARV-471, the company has said it is winding down and results will be presented in San Antonio. Pfizer (maker of Ibrance) is moving it forward, the plans are to have three clinical trials start in 2022; 1) phase 3, ARV-471 alone or with Ibrance; 2) phase 1b, ARV-471 with everolimus and potentially in other combinations; 3) phase 1 neo-adjuvant, hoping to move it to early stage
THANKS, DEE!!!! Hoping you find the next big drug in whatever trial comes next...
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Thanks Cure-ious
ARV-471 gave me 11 months of stable disease!! That’s pretty good considering it was my 6th therapy. I hope it can help others.
Ok big news- I am being considered for a brand new SERD trial https://clinicaltrials.gov/ct2/show/NCT05080842
I will let you all know after I get more data tomorrow.
Dee
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Thanks for sharing that info, Cure-ious. Hopefully they will start things in early 2022. Perhaps some of us will qualify for phase 1b.
AlabamaDee, This is great news and I hope you can get on the trial!
Hugs, Susan
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Alabama Dee, I'm so relieved that you may have a new trial option and am keeping my fingers crossed and sending good vibes your way!
Susan, I am in awe of how you nurture your well being! I have been way too passive and self-indulgent in this area with the predictable results. You are an inspiration.
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Anyone know anything about samuraciclib (CT7001)? There is a Phase I/II trial (https://www.clinicaltrials.gov/ct2/show/NCT03363893) for ER+HER2- patients that is no longer recruiting. The FDA has fast-tracked this drug and the company is presenting at the SABC conference in December.
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Hi Susan, Yes, CT7001 is an oral CDK7 inhibitor, we have been talking about that drug for ages.. One problem was that the pharmas started out testing IV versions then had to start over with oral versions because the IV wasn't going to be competitive, and another problem is they were in the hands of start ups, which can be slow to market
Anyway, CDK7 was first identified as a target for triple-negative breast cancers, with a paper in Cell in 2015 showing that those cancers are "addicted" to CDK7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC45836...
And then later it was found to also work for ER-positive MBCs, and there it was associated with progression on I-F, such that inhibiting CDK7 could make the resistant cancers become estrogen-dependent again. https://pubmed.ncbi.nlm.nih.gov/32340192/
As with everything, we are waiting to hear how good is the drug, how bad are the SEs, and what kind of combinations work best etc, very glad to finally see this drug move along!!!
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SusaninSF, Samuraciclib appears at this juncture to be a promising drug.
Below is an excerpt about it from my book, The Insider's Guide to Metastatic Breast Cancer." The Insider's Guide to Metastatic Breast Cancer: A Summary of the Disease and its Treatments: Loeser, Anne: 9781795860604: Amazon.com: Books
Samuraciclib (CT-7001) (Not Yet FDA-Approved for MBC Patients): Samuraciclib is an oral CDK7 inhibitor that showed encouraging results in a Phase 2 study in combination with fulvestrant in patients with advanced HR+, HER2- BC. 31 patients were with difficult-to-treat disease were enrolled; 81% had visceral disease, including 45% with liver metastasis. All patients previously progressed following treatment with a CDK4/6 inhibitor. Of the 31 patients, 24 were evaluable for response at the time of data cut-off. 17 (71%) had tumor shrinkage, and median Progression Free Survival (PFS) was 16.1 weeks. Notably, patients with no mutation in the TP53 gene had a median PFS of 32.0 weeks. Prolonged disease control was also apparent in patients with no liver metastases at baseline, with median PFS having not yet been reached (at the point of this data cut-off, median PFS would be at least 28 weeks). From: https://www.biospace.com/article/releases/carrick-therapeutics-presents-encouraging-initial-efficacy-for-samuraciclib-ct-7001-in-combination-with-fulvestrant-in-advanced-hr-her2-breast-cancer-patients-at-esmo-congress-2021/
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More on Samuraciclib: Safety and Antitumour Activity of a First-in-Class, Oral (esmo.org)
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Here are some interesting results from a phase 2 trial looking at Keytruda in combination with Imprime PGG (an activator of the innate immune system that reprograms the suppressive immune environment around the tumor). Consistent with earlier findings that those individuals whose cancer subtype switched from ER-positive to ER-negative are more sensitive to immunotherapy, this trial came to the same conclusion:
"Researchers observed a particularly pronounced clinical benefit in a subgroup of patients who initially were diagnosed with ER-positive/PR-positive disease but progressed on endocrine therapy and, prior to treatment, had biopsies that confirmed conversion to triple-negative breast cancer..."
The IMPRIME1 trial included 44 patients, 27% had liver mets. Overall, they found that 27% responded (ie, tumor shrinkage or stable disease) for at least six months.
"Investigators observed pronounced clinical benefit with the combination among a subgroup of 12 patients originally diagnosed with ER-positive/PR-positive disease who underwent prior treatment with endocrine therapy and later converted to triple-negative disease."
In this group, six (50%) achieved response (tumor shrinkage) to the combination, four (33%) achieved stable disease, and six (50%) achieved disease control for 6 months.
In a subsequent publication, they reported: Ten IMPRIME 1 patients were originally ER/PR+, received hormonal Tx and progressed to TNBC. Of these, 5 are confirmed PR (tumor shrinkage), 4 SD (stable disease, 3 are still on treatment), and one had progressive disease. https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.1...
Adding Imprime IGG almost doubled the overall survival compared to Keytruda alone. This trial ended in March, and in January the company announced they had developed an assay for an immune biomarker that is necessary for patients to respond to the Imprime IGG treatment.
https://www.healio.com/news/hematology-oncology/20...
https://finance.yahoo.com/news/hibercell-biodesix-...
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WOW that sounds promising for me Cure! Too bad only Phase 2...
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I have some news. Mary Crowley found a new trial for me. Yay.
On Friday I went for the consent/ screening appointment and scans, etc. one step closer to being accepted. I signed my life away. LOL But, as I understand it, I can still possibly be disqualified depending on the results?!?! Even some of my medications may have to be changed.
It’s called MCMRC IRB #21-20 and ImmVira Ph 1/2 T3011. I will be on the study agent only. Some people will also be on Keytruda.
Basically, they use HSV ( modified) infusions to try and activate my immune system to kill the cancer. Cure ious I’m sure I don’t have the expertise you have to explain this trial.
The schedule doesn’t seem to be as time consuming as the other trials I looked at. I only have to spend two eight hour days at the center each week. Plus, one
lab only appointment each week.
Next week I will have a liver BX and a Brain MRI. My tentative start date is November 29.
Now, for the waiting. UGH to see if I qualify.
If anyone knows more information about this trial, I’d love to hear it.
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Grannax thats great!
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Grannax,
Fantastic news! So wonderful that Mary Crowley is doing the searching for you,
I am still waiting to hear from USC about the ARX-788 trial. In the meantime, trying to stay positive and keep my body in the best shape I can.
Hugs, Susan
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Thanks, Susan. The waiting is so hard. Sure hope you get in.
Thanks, Nicole. I know you’re exploring options. I hope you find the best fit for you.
I’m very glad to have friends here to encourage us
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Susan,
Regarding ARX788, which is an ADC that combines a HER2-directed monoclonal antibody with a new drug (Amberstatin269), they had great results in phase 1. The overall response rate (ORR) was 74% for HER2-positive breast cancer, and 67% in patients with HER2-overexpressing solid tumors (ORR refers to number of people who got tumor shrinkage). Across both populations, the disease control rate (meaning shrinkage or stable for six months) was 100%.
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Thanks, Cure-ious. Those are some impressive stats.
I am SO HOPEFUL!
Hugs, Susan
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Wow, give this some thought...
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Hi all,
After failing to qualify for the CERAN study, I was eligible for 2 others at Sarah Cannon, KAT6 inhibitor and a new trial AC682 SERD trial# NCT05080842 monotherapy
After talking with Dr. Hamilton this morning, we decided to go with the SERD for several reasons.(she called it the PROTAC2)
She said she felt in her gut this was a good next step since I responded with stable disease to the other PROTAC for so long, plus
- the starting dose is high enough they expect clinical significance (the biggest reason to try in my opinion)
- We know the potential side effects from other SERDs,
- I may still qualify for KAT6 inhibitor if this fails, (8 week scan from start date) but she did not know recent specifics of that trial
- there was only 1 spot open in the new SERD and I was in competition for it.
I will probably be in the first 3x3, but I am OK with that. My home MO said I am a trailblazer!!
Dr. Hamilton wants me to come in Wednesday to see her and set it up and save me the spot. Won't know if I have it until I sign the papers, hopefully next week.
Hoping for the best!
Dee
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That’s great news, Dee! So happy for you
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