TEST:

MSK-IMPACT

P1, N=28, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

AlphaTMB improves survival prediction beyond TMB alone, better captures immunogenic tumor profiles, and reflects more accurate patient stratification. This AI derived somatic mutations pathogenicity scoring represents a step toward personalized immuno-oncology and merits further validation in prospective studies.

A super-high TMB threshold of ≥ 25 mut/Mb by MSK-IMPACT identifies a distinct subset of melanoma patients who achieve truly exceptional benefit, with nearly one in two attaining clinical cure following ICB therapy. These data support prospective validation of "hypermutation" as a clinically actionable biomarker, refine patient counseling, and inform trial stratification in the era of personalized cancer immunotherapy.

NRAS-mutant melanomas harbor a coordinated transcriptional program within 1p13.2, driven by CNV gains. This locus contains genes with potential druggability, offering new avenues for combinatorial targeting alongside mitogen-activated protein kinase pathway inhibition.

P1, N=14, Not yet recruiting, PMV Pharmaceuticals, Inc

P1/2, N=52, Recruiting, Memorial Sloan Kettering Cancer Center

Kaplan-Meier analysis of R-CHOP-treated patients with DLBCL-NOS revealed that those with MCD, BN2, and A53 subtypes had poorer overall survival than those with EZB and ST2, particularly among patients with concurrent MYC/BCL2 DE. Using a clinically applicable NGS panel, we successfully implemented the LymphGen classification system. This study underscores the distinct genetic landscape of Korean DLBCL and highlights the utility of LymphGen in identifying high-risk subgroups, providing a basis for prognostic stratification and therapeutic optimization.

RRASQ87L and RRAS2Q72L are recurrent, oncogenic, and potentially actionable drivers in NSCLC. Our study supports the inclusion of RRAS/RRAS2 into routine molecular diagnostic panels for precision oncology and provides preclinical rationale for investigating the potential therapeutic utility of pan-RAS inhibitors for patients with RRASQ87L/RRAS2Q72L-mutant lung cancers.

The DDR-IF score unifies measures of genomic instability and immune contexture to identify a therapeutically vulnerable subset of ES-SCLC patients most likely to benefit from PARP-ICB synergy. It represents a promising, though exploratory, framework for personalizing immunotherapy in ES-SCLC, whose clinical utility requires confirmation in prospective multicenter trials.

Notably, 7 individuals (22%) experienced severe or fatal therapy-related toxicities, despite many lacking other clinical features of a TBD. These findings support that RTEL1 R1264H can act in an autosomal dominant fashion and confer TBD disease risk, albeit with low penetrance, and may increase susceptibility to treatment-related complications.

PRNRP represents a distinct KRAS-mutant RCC subtype with unique metabolic and genomic features linked to its distal nephron origin. This contrasts with the genomic complexity and aggressive clinical behavior observed in KRAS-mutant PRCC and URCC, highlighting the need for subtype-specific diagnostic criteria and therapeutic strategies.

This study analyzed 321 tumor samples from 244 Chinese patients with genitourinary cancers using targeted NGS. Distinct mutational landscapes and PD-L1-associated genes were identified across bladder, renal, and prostate cancers. Comparative analysis with Western cohorts revealed population-specific genomic heterogeneity, supporting region-tailored precision oncology.