KRAS G12C

P1/2, N=534, Recruiting, Revolution Medicines, Inc. | Phase classification: P1 --> P1/2 | N=210 --> 534 | Trial completion date: Nov 2026 --> Jun 2029 | Trial primary completion date: Nov 2026 --> Dec 2028

In this phase I study, we test a pooled synthetic long peptide vaccine targeting the six KRAS mutations (G12V, G12A, G12R, G12C, G12D, G13D) with ipilimumab and nivolumab in resected pancreatic adenocarcinoma. The vaccine also generates cross-reactive T cells that recognize more than one mutant KRAS antigen. These findings support the safety and diverse anti-tumor immunity of mutant KRAS vaccines (NCT04117087).

We provide recommendations for oncology trial designs that consider factors such as informative censoring, crossover, and subsequent therapies, with the goal of preserving the interpretability of OS outcomes and more accurately reflecting the true treatment effect. An R Shiny application is available to facilitate implementation.

P=N/A, N=13, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Among different gene alteration subgroups for advanced NSCLC, the efficacy of first-line ICIs did not differ with statistical significance, with high PD-L1 expression as a predictive factor for better survival. In KRAS mutant patients, KRAS G12C mutation or TP53 co-mutation might indicate improved survival.

EBUS-TBNA's role in diagnosing various conditions, especially primary lung cancer, is clear. Clinically, EBUS-TBNA provides genetic diagnoses, which can enable immunotherapy. Patient satisfaction is high, with patients expressing relief after the procedure and finding the staff exceptional.

P3, N=160, Active, not recruiting, Amgen | Trial completion date: Jan 2026 --> May 2026

Stratified two-stage TMP reliably identifies actionable alterations in PC patients, with potential therapeutic benefit. The proposed TMP algorithm might be as effective, yet more feasible and economic compared with comprehensive upfront testing.

Methods We performed whole exome sequencing (WES), bulk RNAseq, multiplex immunofluorescence (mIF) and chromogenic immunohistochemistry (IHC) on tumor tissue and flow cytometry of the peripheral blood to study longitudinal changes following the combination of avelumab with utomilumab (a 4-1BB agonist) (arm A), PF-04518600 (an OX40 agonist) (arm B), utomilumab and PF-04518600 (arm C) and utomilumab and radiotherapy (arm D) in phase I/II study (NCT03217747). Conclusions Our findings, though limited, highlight genomic differences between histologic subsets and outcome as well as the need for combination strategies that drive the recruitment and/or priming of anti-tumor T cells and address low immune permissive tumor states in patients with advanced solid tumors. Clinical trial registration: This clinical trial was registered on clinicaltrials.gov NCT03217747.

In our cohort, KRAS mutations were more prevalent in PLMAC than PLNMAC (72% vs. 40%, P < 0.05). However, the KRAS G12C variant was significantly less frequent in PLMAC compared to PLNMAC (19% vs. 47%, P < 0.05), suggesting that patients with PLMAC are less likely to benefit from KRAS G12C-targeted therapy. These findings underscore the importance of comprehensive KRAS genotyping and highlight the need for developing additional KRAS variant-targeted therapy for patients with PLMAC.

Compared to results from established architectures such as Inception-v3 on the same WSIs, our model demonstrated significantly improved performance for most features. With further optimization, our model could support triaging for molecular testing and inform precision treatment strategies for NS-LUAD patients.

This combination induces durable immune memory in immunogenic models but not in nonimmunogenic settings. Our findings underscore key differences between KRAS G12D and G12C mutations in shaping lung cancer biology, reveal distinct resistance dynamics under long-term targeted therapy, and uncover immune-mediated mechanisms specific to KRASG12D inhibition with direct clinical and translational relevance.