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Any combo that targets PD-1 + OX40 ... on TILs has been futile. Overcoming the elephant in TME has been daunting for the tied, old TILs. There is no turning back the old biological clocks in-vivo.
More pd-1 combo flop
Merck (NYSE:MRK) announced on Tuesday that the company decided to stop its Phase 3 KEYLYNK-010 trial for a combination therapy involving its anti-PD-1 therapy, Keytruda, and PARP inhibitor, Lynparza, as a third-line option for metastatic castration-resistant prostate cancer.
The decision followed a planned interim analysis in which the therapeutic combination was found to have no benefit in overall survival compared to the control arm, one of the dual primary endpoints of the study.
https://seekingalpha.com/news/3813523-merck-halts-late-stage-prostate-cancer-trial-for-keytruda-combo
IL-2 flop not good news for TIL
Bristol Myers Squibb and Nektar were informed that the study did not meet the primary endpoints of progression-free survival (PFS) and objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR). The DMC notified the companies that the third primary endpoint of overall survival (OS) did not meet statistical significance at the first interim analysis.
your post raised the price of donut by 1 cent
ACT KOLs and Wall St. mouth pieces do not follow Higgins until they see $$
Finding Needles in a Haystack
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664211/
By the time Brody completes the trial, anti-PD1 will be replaced by another back bone of immunotherapy.
1 CR for the pt. with highest number of neoAgs and received the highest dose of IL-2.
Trying to increase APC in TME has been a big challenge. With Planet, you can control the ratio ex-vivo.
https://clinicaltrials.gov/ct2/show/NCT04491084?term=CDX-1140&draw=2&rank=7
Interleukin-2 (IL-2) is a central T cell cytokine that promotes T cell proliferation and effector function; however, toxicity due to its pluripotency limits its application to enhance CAR T cell immunotherapy.
https://www.science.org/doi/10.1126/scitranslmed.abg6986#:~:text=Interleukin%2D2%20(IL%2D2)%20is%20a%20central%20T,enhance%20CAR%20T%20cell%20immunotherapy.
As of February 18, 2021, there were approximately 51.0 million shares of common stock issuable upon the exercise of warrants, having a
weighted average exercise price of $2.26 per share
on demand for the early birds. Now they have to wait 3 months.
Where is that CR after listening to the CC?
First 10 pts recruited in 2021 were lucky to get special treatment.
GNCA should just expand Titan to include all cancers. Atlas don't care. Let see the new VP work on the FDA.
What is the most popular bridging therapy for GEN011?
Bridging therapy is new.
How long did these analysts follow GEN011?
24 hrs
You can buy a donut or billion T cells for a buck today.
Anti-PD1 don't work in tumors where inhibigens outnumber neoAgs. Surprising
CSC, NSCLC, SCLC, SCCHN, and melanoma. A median of 2.1bn monocytes and 6bn T cells were cryopreserved from apheresis products (N=17)
ATLAS screens identified a mean of 13±4 neoAgs and 11±3 Inhibigens, resulting in an average of 13 (range 2-30) unique neoAgs in each PLANET manufacturing process.
KPC pancreatic cancer. Out of 73 total non-synonymous mutations, we successfully identified 14 CD4+ and 15 CD8+ true neoantigens, and 16 CD4+ and 18 CD8+ Inhibigens. This is the first known comprehensive characterization of endogenous antigens in this model.
Is this MD the lead presenter? I have to change my call to 1 SD, 2 PR melanoma + 1 SD, 1 PR H&N
Maura L. Gillison, M.D., Ph.D., is Professor of Medicine, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX. She is a recognized expert in head and neck medical oncology
9 minimum neoAgs in pts. targeted by GEN11 compared to PSMA targeted by PSTX CART. That is 9:1 broad.
Replace lymphodepletion with SBRT before GEN-011 cohort A is worth a try. I think ASCO is more likely. Adding John Lunger to the board is telling.
Working like a vaccine
Neoadjuvant Treatment for Certain Adult Patients with Resectable Non-Small Cell Lung Cancer
358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy on the same day every three weeks for up to three cycles, or platinum doublet chemotherapy every three weeks for up to three cycles, followed by surgery
https://www.businesswire.com/news/home/20220301006264/en
Eric Dollins, PhD as VP of Regulatory Affairs
2 SD in cohort A. 3 PR in cohort B. All melanoma
nonessential component
2 SD/3 PR is my call
financial results and corporate update conference call and live audio webcast on Thursday, March 10th at 8:30 a.m. E.T.
TIL needs lots of help to stay fresh.
activation of the self-ligand SLAMF7 immune receptor on T cells induced STAT1 and STAT3 phosphorylation, expression of multiple inhibitory receptors, and transcription factors associated with T cell exhaustion
https://pubmed.ncbi.nlm.nih.gov/33288545/
Bifidobacterium in gut vs. e.coli in Atlas
https://www.nature.com/articles/s41591-022-01695-5
To date, no biomarkers have been formally associated with PTI. More research to find biomarkers of PTI is needed.
https://www.protumorinflammation.com/about-pti/
KOLs think PD-L1/TMB is the back bone. They can't stand GEN-011 which will break their narratives. I think chemo removes pro tumor CD8/CD4.
DuoBody®-PD-L1x4-1BB (GEN1046) is an investigational, first-in-class, bispecific immunotherapy
disease control (defined as stable disease [SD] or better per
Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1 (29)) occurred in 40 of 61 patients (65.6% [95% CI: 52.3–77.3]; Fig. 5A). Four patients achieved a partial response (PR)
https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-21-1345/681604/Preclinical-Characterization-and-Phase-I-Trial
I did not say this: Tied, old, blind and addicted to IL2
TIL + anti-PD1 mAb combo is 1 in hundreds combos. Lots of competitions.
You are right.
Patients previously treated with PD-1 or MAPK inhibitors are significantly less likely to develop durable objective responses to ACT-TIL.
https://ascopost.com/news/august-2021/patients-with-melanoma-previously-treated-with-pd-1-or-mapk-inhibitors-may-be-less-likely-to-respond-to-act-til-therapy/
Treg was depleted by chemo in cohort A.
My money is on different cohort B. I don't think Treg is the big elephant in TME.
GlaxoSmithKline’s big gamble on a cancer drug developed by Germany’s Merck KGaA looks unlikely to pay out, after bintrafusp alfa failed to outperform US-based Merck & Co’s Keytruda in a lung cancer trial.