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. ⁦@pashtoonkasi⁩ ⁦@mgfakih⁩

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. @mgfakih @pashtoonkasi

Excellent presentation by @MeghanMooradian from @DFCI presenting @UPMCHillmanCC 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

(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. @Farnaldez3, @PatelOncology, @DmitriyZamarin and others. https://t.co/FOAIXenewM

(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. @jitcancer

Wonderful work at @sitc2024 from talented @PittDeptofMed IM resident @Ellienasr regarding biomarkers of severe irAEs TMOS and IMC in I/O treated cancer. @UPMCHillmanCC @PittHealthSci @PittTweet @PittIMChiefs @sitcancer

Wonderful work from talented @PittDeptofMed IM resident @kseniya_y_a regarding the predictive capacity of tumor-informed ctDNA monitoring in I/O treated #melanoma. @UPMCHillmanCC @PittHealthSci @PittTweet @PittIMChiefs

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 @RyanAugustinMD! https://t.co/jHA2yFPoKm

(5/5) Great team science, with fantastic collaborators: @HassaneZarour, @GiorgioTrinchieri. @PittHealthSci @UPMCHillmanCC @NCI_CSSI #CPTAC. Thanks to @jsmithymd for a great editorial! Read here: https://t.co/cOBXxE1ZPx.

(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 ( https://t.co/k7RzWJh4Vv).

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

(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.

(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

(3/3) Surprising Gr5 myocarditis in 2 pts (see Cavalcante et al, same issue). CD28 co-stim is fantastic, but tox mitigation is key. Great work by co-authors @AllisonNaumovski, @LudiCa19862, @_vosko @RachelSanbornMD, @JustinGainor and others. @UPMCHillmanCC

(2/3) Early expansion of Ki67+CD4+ and Ki67+CD8+ T cells that peaked at day 8 akin to prior observations by John Wherry, Rafi Ahmed in melanoma and NSCLC (left). Efficacy signal in RCC with responses in PD-1 naive and PD-1 R/R tumors (right).

(1/3) ALPN-202 (davo) is a novel agent that inhibited PD-1/CTLA-4 with PD-L1-dependent CD28 co-stim. Dose-escalated singly (NEON-1) & with pembro (NEON-2). Dose-dependent PK both as mono and combo with moderate ADA incidence (14% vs. 24%).

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. ⁦@UPMCHillmanCC⁩

Today @bcbs_companies 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 @TriSalusLifeSci Chandra Ghosh and colleagues for this report detailing preclinical efficacy of PEDD-delivered #TLRa nelitolimod into liver mets( https://t.co/leaddephOB). Clinical data from #PERIO-01 previously been presented by @DrSapnaPatel at SITC 2023.

Congratulations to Florent Amatore, outstanding @aphm_actu 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. @UPMCHillmanCC @PittHealthSci