MSI-H/dMMR

P2, N=16, Active, not recruiting, Nicholas DeVito, MD | Recruiting --> Active, not recruiting

Oral Lm-based cancer vaccines targeting CRC elicit robust, widely disseminated, and persistent tumor-specific immune responses in mice. These vaccines limit CRC development when administered prophylactically and provide tumor control when administered therapeutically with ICI. Thus, oral delivery of Lm-based cancer vaccines coupled with ICI may provide improved control of CRC progression in clinical application.

She started combination therapy with ipilimumab and nivolumab, achieving complete metabolic and imaging response as confirmed by PET-CT at 12 months...She started treatment with pembrolizumab, achieving a sustained complete response at 12 months...Both cases illustrate the remarkable clinical benefit of immunotherapy in patients with early peritoneal recurrence of MSI-H/dMMR colon cancer, which is usually associated with poor prognosis. These cases highlight the need to consider the molecular profile in therapeutic planning and reinforce the emerging value of immunotherapy as a cornerstone in the management of these cases.

MSI testing which has been used historically to identify patients with Lynch Syndrome and evaluate the severity and prognosis of MSI carcinomas now plays an important role in identifying patients who will benefit from targetable therapy. MMR study therefore recommended in all cases of endometrial carcinomas and detection of MMR proteins by IHC can indirectly reflect the status of MSI and is a reliable method of MSI detection.

Initial chemotherapy with FOLFOX (oxaliplatin, fluorouracil, and folinic acid) was initiated; however, a microsatellite instability-high (MSI-H) status was identified, and the treatment was promptly switched to pembrolizumab. Additionally, a brief meta-analysis of 10 studies comprising 72 patients with MSI-H/mismatch repair-deficient SBA revealed an objective response rate to immune checkpoint inhibitors of 65.3%. This case highlights the potential of pembrolizumab for the curative resection of an initially unresectable MSI-H SBA.

Three KRAS-mutated tumors also had at least focal mesonephric-like histology. Although rare, p53 wild-type tumors represent a small subset of OCS that show distinct clinical and histologic features and are largely driven by KRAS mutations.

This study demonstrates that tumor-specific DNA methylation changes, particularly when evaluated using multi-gene panels can enhance prognostic stratification in GC. These findings support the potential use of methylation-based biomarkers for personalized management of GC.

Combining biomarker-driven immunotherapy and targeted approaches such as PD-1 blockade in MSI-H or EBV-positive tumors, HER2-directed therapy, and CLDN18.2 inhibition, has demonstrated a paradigm shift in the clinical management. This review highlights a pathologist-centered perspective on molecularly defined subgroups, actionable biomarkers, and evolving therapeutic paradigms in CRC and GEJ carcinoma, advancing precision oncology.

P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P3, N=123, Not yet recruiting, Shanghai JMT-Bio Inc.

Treatment of LA HNSCC is multimodal and may include concomitant cisplatin-based chemoradiotherapy (CRT) or surgery; however, recurrence rates are high, and there is an unmet need for new treatments. The primary endpoint is event-free survival, with overall survival as a key secondary endpoint; safety and tolerability, pharmacokinetics, immunogenicity, biomarkers, and patient-reported outcomes will also be assessed. www.clinicaltrials.gov identifier is NCT06256588.