Anti-PD-1 efficacy in hepatocellular carcinoma can work through B cells, not only T cells. In a mechanistic study alongside a phase 2 trial of perioperative anti-PD-1 therapy in resectable recurrent HCC, late-recurrence patients showed two subtypes with T cell- or B cell-dominant tumor responses; B cell-dominant tumors had somatic hypermutation-driven antibodies against HBV core antigen within tumor tertiary lymphoid structures. In mice, HBcAg-reactive antibodies drove complement-mediated antitumor activity that enhanced anti-PD-1 response.
Genome-wide in vivo CRISPR screens of human T cells in solid tumours identify two GPCR-related targets: the P2RY8-Gα13 axis limits T cell tumour infiltration, and GNAS drives T cell dysfunction, with Gαs acting as a convergent node downstream of multiple suppressive GPCRs. GNAS knockout made T cells resistant to suppressive cues and improved efficacy in CAR and TCR models across diverse solid tumours, and combined P2RY8-GNAS knockout further enhanced tumour control.
The Phase 3 randomized, double-blind INTerpath-001 trial of Moderna's personalized neoantigen vaccine intismeran plus pembrolizumab enrolled 1137 post-surgery high-risk patients, randomized 2:1 to intismeran 1 mg every 3 weeks plus pembrolizumab 400 mg every 6 weeks or pembrolizumab alone. Topline results were positive, with the effect size awaiting full unblinding.
Why it matters: First positive Phase 3 readout for a personalized neoantigen therapy, with enrollment size and combination regimen given as a benchmark for comparable pipelines.
In an updated phase III CARTITUDE-4 analysis, the BCMA-targeted CAR-T therapy cilta-cel continued to extend PFS over standard care in patients with lenalidomide-refractory relapsed/refractory multiple myeloma, and the OS difference crossed the prespecified statistical boundary at the second interim analysis. Results, with a median follow-up of 33.6 months, were published in The Lancet Oncology in January 2026.
Why it matters: The second interim OS analysis crossed the prespecified boundary, adding randomized OS evidence for BCMA CAR-T in lenalidomide-refractory multiple myeloma.
Ipsen has completed its acquisition of U.S. clinical-stage company Kartos Therapeutics, about two months after signing the definitive merger agreement on June 29, 2026. The deal totals $1.75 billion, comprising a $450 million upfront payment and up to $1.3 billion in regulatory and sales milestone payments, giving Ipsen the Phase III oral MDM2 inhibitor navtemadlin (KRT-232) for myelofibrosis. The global Phase III POIESIS trial, enrolling over 600 patients at more than 250 centers on top of ruxolitinib in TP53 wild-type patients with inadequate ruxolitinib response, continues, with topline data expected in 2027.
Simcere's Kocela (trilaciclib hydrochloride for injection) won NMPA approval on August 24 for a new indication: reducing chemotherapy-induced myelosuppression in relapsed extensive-stage small cell lung cancer patients before topotecan-containing regimens. The CDK4/6 inhibitor, in-licensed from G1 Therapeutics, now covers bone marrow protection across first-line and second/third-line chemotherapy for extensive-stage SCLC, making it the only drug approved in China for the full treatment course.
Response to intracerebroventricular bivalent CAR T cell therapy in recurrent GBM was defined not by CAR T cell activation, which occurred in all patients, but by remodeling of the endogenous immune compartment in longitudinal CSF and tumor samples. Responders showed expansion of cytotoxic natural killer cells, while non-responders showed regulatory T cell expansion and abundant baseline immunosuppressive scavenger myeloid cells. The work points to combinatorial strategies that modulate host immunity to improve treatment.
Moderna and Merck's jointly developed mRNA cancer vaccine intismeran autogene reduced the risk of recurrence or spread in patients whose melanoma had been surgically removed, in a trial of 1,137 volunteers. After the top-line results, some investors and longtime skeptics of mRNA technology still called for waiting for the full data. The article recounts an off-site Moderna leadership meeting in March 2023, tracing the vaccine's development from concept to its pivotal readout.
Why it matters: The article traces the mRNA cancer vaccine from widespread doubt to positive readout through Moderna executives' recollections, useful as background for similar programs.
Adjuvant selpercatinib for up to 3 years after definitive therapy sharply reduced recurrence in RET fusion-positive NSCLC. In the 109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib versus 61% with placebo (hazard ratio 0.17; P<0.001), and blinded independent central review was consistent. The findings extend selpercatinib from advanced disease into the early-stage, curative-intent setting.
Moderna and Merck jointly announced that their personalized neoantigen mRNA vaccine for melanoma, intismeran autogene (mRNA-4157, V940), met both the primary endpoint of recurrence-free survival and the key secondary endpoint of distant metastasis-free survival in the Phase III INTerpath-001 trial. On the news, Moderna shares closed up 177% in one day, Merck rose more than 12%, and the Nasdaq Biotechnology Index climbed 6.39% to a record high.
Why it matters: Reports that the Phase III INTerpath-001 trial met both the RFS primary endpoint and the DMFS key secondary endpoint, a key benchmark for personalized mRNA cancer vaccine platforms.
PathPrism, an interpretable AI framework, encodes tissue architecture into pathologically informed spatial features to model prognosis, molecular alterations, and therapy response. Applied to 7,000 patients with colorectal cancer across 11 cohorts, it uncovered hundreds of biomarkers predictive of survival, MSI, BRAF, and TP53 mutations, and stratified chemotherapy benefit in stage II/III disease. It also uses large language models to generate hypotheses and includes VirtualWSI for semantic perturbation.
An AI system for liver malignancy diagnosis on CE-CT, LiON, reached an AUC of 0.975 in retrospective validation across 22,251 patients from multicenter and real-world cohorts, and held performance in patients with hepatic steatosis (AUC 0.971) and cirrhosis (AUC 0.924). In a single-arm trial of 10,333 patients in routine practice, LiON served as an additional AI reader and met its primary endpoint with an AUC of 0.952. AI-human collaboration identified 51 previously overlooked lesions, 15 of them malignancies, prompting 37 amended reports and 22 multidisciplinary team escalations.
Merck and Moderna jointly announced that the Phase III INTerpath-001 trial of intismeran autogene (V940/mRNA-4157) combined with KEYTRUDA (pembrolizumab) as adjuvant therapy for completely resected stage IIB-IV melanoma met both its primary endpoint of recurrence-free survival (RFS) and key secondary endpoint of distant metastasis-free survival (DMFS). The companies plan to present detailed data at an upcoming international medical conference.
Why it matters: INTerpath-001 met both RFS and DMFS in adjuvant melanoma, informing head-to-head comparison of individualized neoantigen mRNA therapy with PD-1 monotherapy adjuvant.
Moderna and Merck have announced positive topline results from the late-stage INTerpath-001 study of the personalized neoantigen therapy intismeran autogene (V940/mRNA-4157) combined with KEYTRUDA as adjuvant treatment after surgery for high-risk melanoma. The companies described it as the first positive late-stage readout for a personalized neoantigen therapy and for mRNA cancer treatment.
Why it matters: Brief lists the drug, trial and indication for the first positive late-stage neoantigen readout, and uses it to discuss domestic pipelines.
Pre-surgical ctDNA clearance identifies patients most likely to benefit from perioperative nivolumab in resectable NSCLC: 66% of nivolumab-treated patients with evaluable ctDNA cleared it before surgery, and half of those had pathologic complete response, versus 38% clearance and 12% pCR on placebo. Nivolumab also prolonged EFS in patients with alterations in KEAP1, STK11, CDKN2A and/or SMARCA4 (HR 0.48, 95% CI 0.28-0.83). A machine-learning model ranked ctDNA clearance among top predictors of longer EFS.
Structures of N-terminal acidic (NtA) motif-mediated asymmetric BRAF dimers bound to MEK1 provide the missing structural support for the long-standing model that the NtA promotes activating asymmetric RAF dimerization. Cellular and biochemical data show the NtA is dispensable for KRAS-mediated BRAF recruitment to the plasma membrane but is required for full catalytic activity, corroborated by a post-catalytic structure bound to Ser222-phosphorylated MEK1. This resolves a disconnect between RAF cancer genetics and structural biology.
Thiotepa-based HCT-ASCT consolidation after MATRix induction significantly improved 3-year progression-free survival in newly diagnosed primary CNS lymphoma compared with non-myeloablative R-DeVIC: 78% versus 51% in the 229 analysed patients. HCT-ASCT caused more adverse events per patient and five fatal consolidation-related events versus two with R-DeVIC. The findings establish HCT-ASCT as the preferred consolidation strategy in fit patients.
SMD2, a core spliceosomal component, acts as a direct reader of pseudouridines, binding ψ-modified RNA preferentially over unmodified uridines in human cells. SMD2 works with PUS family enzymes to regulate alternative splicing by recognizing ψ residues near exon-intron junctions. SNRPD2, the gene encoding SMD2, is overexpressed in multiple cancers and is essential for tumor cell proliferation, pointing to a therapeutic target.
A prognostic atlas links cell type-resolved gene expression to overall survival in pancreatic ductal adenocarcinoma, integrating single-nucleus RNA-seq and longitudinal data from 152 patients and profiling 1.2 million cells, plus 3.1 million cells by spatial transcriptomics correlated with therapeutic response. The atlas identifies PLOD2, whose elevated expression predicts poorer outcomes across eight cell types, and a proof-of-concept degrader compound inhibits PDAC progression in vivo. The ctPANDA platform makes cell-type-level prognostic insights available to the research community.
Merck and Moderna announced that the mRNA cancer vaccine intismeran autogene (V940) combined with Keytruda met the primary endpoint in the Phase III INTerpath-001 study in melanoma. Moderna closed the prior trading day with a market value of about $25 billion, up 176.97% in one day and approaching the $70 billion mark, while BioNTech has withdrawn from this direction.
Why it matters: INTerpath-001 hit its Phase III primary endpoint and Moderna's market value rose nearly 177% in a day, contrasting with BioNTech's retreat in the same field.
