Congratulations to Florent Amatore, outstanding AP-HM - Hôpitaux Universitaires de Marseille physician scientist, presenting data from a pilot neoadjuvant study of #pembrolizumab in cSCC. N=26, pCR 59%, improved EFS with responders, very exciting spatial domain data from @PredXBio. UPMC Hillman Cancer Center Pitt Health Sciences

Today BlueCrossBlueShield denied coverage of scans to my patient with #metastaticmelanoma, requiring a peer-to-peer for standard of care imaging. To add insult to injury, they explicitly say that an NP or PA cannot do the peer-to-peer, must be an attending. These highly trained APPs

Congratulations to TriSalus Life Sciences Chandra Ghosh and colleagues for this report detailing preclinical efficacy of PEDD-delivered #TLRa nelitolimod into liver mets(jitc.bmj.com/panels_ajax_ta…). Clinical data from #PERIO-01 previously been presented by Sapna Patel at SITC 2023.

Great work by HCC summer academy student @RomanAllen who evaluated role of non-nutritive sweeteners (NNS) in affecting outcomes to cancer immunotherapy. Akin to preclinical observations, NNS may impede ICI efficacy. More to come. ⁦UPMC Hillman Cancer Center⁩

(1/5) TLR9 plays a fundamental role in pathogen recognition by recognizing PAMPs and activating innate immunity. TLR9 agonists have been studied in cancer with conflicting results. Vidu (CMP-001) is a G10 CpG within a Qb-derived VLP with single agent efficacy in PD-1 R/R melanoma

(2/5) We explored neoadj vidu+anti-PD-1 (nivo) in a CMPI/REGN-sponsored ISR in high-risk resectable mel. Neoadj CpG/PD-1 resulted in high rates of major pathologic response (MPR 55%) with improved 1-/2- year RFS (94%/88%), DMFS (94%/94%) and OS (100%/100%) in MPRs.

(3/5) Tumor eval using NanoString GeoMx and ST (10x Genomics) implicated intratumoral pDCs and myeloid cells in vidu anti-tumor effects. Significant peripheral immune activation by flow. LCMS #proteomics by #CPTAC colleagues Fred Hutch Cancer Center identified a peripheral PD signature.

(4/5) Gut microbiota of CpG and PD-1 responders were antithetical but recapitulated preclinical findings from prior (DOI:10.1126/science.1240527). Perhaps the gut microbiome is a more treatment-specific biomarker as suggested by Gunjur et al (rdcu.be/dYK3L).

(5/5) Great team science, with fantastic collaborators: @HassaneZarour, @GiorgioTrinchieri. Pitt Health Sciences UPMC Hillman Cancer Center @NCI_CSSI #CPTAC. Thanks to Jim Smithy for a great editorial! Read here: cell.com/cancer-cell/fu….

Enjoyed speaking ASCO #ASCODailynews on evolving #Melanoma treatments - Neoadj/adjuvant ICI, TILs, PRAME CD3 & TCRs - so much happening! Most important, organizing medical teams to optimize patient outcomes. Great to see rising star Ryan C. Augustin! dailynews.ascopubs.org/do/podcast-adv…

Wonderful work from talented PittDeptofMed IM resident Kseniya Anishchenko, MD regarding the predictive capacity of tumor-informed ctDNA monitoring in I/O treated #melanoma. UPMC Hillman Cancer Center Pitt Health Sciences University of Pittsburgh Pitt Medicine Chiefs

Wonderful work at @sitc2024 from talented PittDeptofMed IM resident Ellie regarding biomarkers of severe irAEs TMOS and IMC in I/O treated cancer. UPMC Hillman Cancer Center Pitt Health Sciences University of Pittsburgh Pitt Medicine Chiefs Society for Immunotherapy of Cancer

(1/2) MEDI5395 is a recombinant attenuated NDV that expresses GM-CSF. In a Ph1 study of MEDI5395/Durva in treatment-refractory advanced cancer, viral shedding in blood (Fig. S2), saliva (Fig. S3A, top) and urine (Fig. S3B, bottom) increased in a dose-dependent manner. Journal for ImmunoTherapy of Cancer

(2/2) Efficacy of MEDI5395/Durva was low (ORR 10%, DCR 31%). Rx ↑CD8+ TIL density and PD-L1 expression (left), & ↑ cytotoxic T cell and IFN gene expression in tumor (right) - underscoring MoA. Fernanda Arnaldez, Sandip Patel MD FASCO, Dmitriy Zamarin MD PhD and others. bit.ly/492Miok

Excellent presentation by Meghan Mooradian from ADuong presenting UPMC Hillman Cancer Center led Neo-Mel-T trial evaluating neoadjuvant anti-TIM-3+anti-PD-1 vs. neoadjuvant anti-PD-1 in high-risk resectable #melanoma. MPR 56%, 1-year RFS 87% with no surgical delays, 15%TRAE with dostar/cobo

1/2: Fc-active CTLA-4 antagonists produce dramatic results in cold tumors eg MSS CRC. Efficacy is often associated with high irAE incidence affecting drug exposure. Vilastobart (XTX-101) is a differentiated Fc-active anti-CTLA-4 which is TME selective. Dr. Marwan G. Fakih Pashtoon Kasi MD, MS

2/2: Fakih et al report on efficacy of this agent in combination with Atezo in non - liver met MSS CRC. ORR 26%, 25% GR3+ irAE, 5% treatment discontinuation rate. Responses are dramatic, deep, and durable. ⁦Pashtoon Kasi MD, MS⁩ ⁦Dr. Marwan G. Fakih⁩