NRAS wild-type

These findings highlight the complex interplay between molecular subtypes, clinicopathological features, and survival outcomes in early CC. Further research is needed to elucidate underlying mechanisms and develop personalized treatment strategies.

Importantly, treatment of mice with FGTI-2734 inhibited sotorasib-induced ERK reactivation in KRAS G12C PDX, and treatment of mice with the combination of FGTI-2734 and sotorasib were also significantly more effective at suppressing in vivo the levels of P-ERK in sotorasib-resistant human KRAS G12C lung cancer xenografts as well as a PDX. Our findings provide a foundation for overcoming sotorasib resistance and potentially improving the treatment outcomes of KRAS G12C lung cancer.

P1, N=325, Active, not recruiting, Exelixis | Trial completion date: Nov 2024 --> May 2027 | Trial primary completion date: Nov 2024 --> Aug 2026

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Sep 2024 --> Sep 2025

P3, N=480, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Further, G48C, Q43K, and E37K all have less negative ΔG values, indicating a weaker GDP-binding affinity compared to wild-type NRAS. Taken together, the results suggest that oncogenic readouts of NRAS mutants are codon- and mutation-specific, with potential repercussions on the aggressiveness, resistance, and therapeutic response.

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Trial primary completion date: Aug 2024 --> Jul 2025

In case of failure to enroll patients in innovative clinical trials, second-line ipilimumab still represents an effective therapy in patients with metastatic wildtype melanoma and in the absence of brain metastases.

P1/2, N=301, Recruiting, Eisai Inc. | Phase classification: P1 --> P1/2 | N=181 --> 301 | Trial completion date: Mar 2027 --> Nov 2026 | Trial primary completion date: Mar 2027 --> Nov 2026

P2, N=58, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Trial completion date: Jul 2024 --> Dec 2024

Preliminary results of the MatchMel study revealed a variety of molecular mutations in WT melanoma pts. NF1 alterations appeared to be linked with Hi-TMB, which was associated with response to immunotherapy.

P2; N=84 --> 12

P2, N=56, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Mar 2024 --> Dec 2024

Our studies show that the NRASQ61R mutation in endothelial cells induces Ang-2 expression in vitro and in vivo. In cultured human endothelial cells, NRASQ61R drives elevated Ang-2 through MAP kinase and mTOR-dependent signaling pathways.

Here we describe RMC-7977, a reversible, tri-complex RAS inhibitor with broad-spectrum activity for the active state of both mutant and wild-type KRAS, NRAS and HRAS variants (a RAS(ON) multi-selective inhibitor). Thus, RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRAS-mutant solid tumours (ClinicalTrials.gov identifier: NCT05379985).

Patients with heavier versus lower weights had lower mortality risk, which was more pronounced for BRAF-mutated patients. These relationships highlight the importance of demographic and pathologic relationships to aid in risk assessment and personalize treatment plans.

P1, N=181, Recruiting, Eisai Inc. | Trial completion date: Oct 2024 --> Mar 2027 | Trial primary completion date: Oct 2024 --> Mar 2027

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2024 --> May 2023

P3, N=464, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Recruiting --> Active, not recruiting | Trial completion date: Jun 2021 --> Dec 2024 | Trial primary completion date: Jun 2021 --> Jul 2023

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting | N=362 --> 74

P=N/A, N=51, Recruiting, Shanghai Minimally Invasive Surgery Center | Trial primary completion date: Jun 2023 --> Aug 2024

The diagnosis of SWI/SNF-deficient undifferentiated carcinoma can be challenging. Correlation with clinical findings, in conjunction with IHC work-up and molecular analysis, is of utmost importance to arrive at the appropriate diagnosis and exclude potential mimics.

P1, N=325, Active, not recruiting, Exelixis | Trial primary completion date: Nov 2023 --> Nov 2024

P1, N=715, Recruiting, Taiho Pharmaceutical Co., Ltd. | N=367 --> 715 | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

P2, N=24, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Jan 2026 --> May 2023

P2, N=22, Active, not recruiting, Academic and Community Cancer Research United | Recruiting --> Active, not recruiting

P=N/A; N=500 --> 199 | Trial completion date: Nov 2025 --> Dec 2023 | Recruiting --> Terminated | Trial primary completion date: Nov 2024 --> Dec 2023; Low accrual

P1/2, N=48, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2023 --> Jun 2025

P3, N=673, Active, not recruiting, Ludwig-Maximilians - University of Munich

P3, N=419, Active, not recruiting, Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) | Trial primary completion date: Jun 2024 --> Jun 2025

The mPFS contribution in the BRAF mutant subgroup with poor prognosis is promising, as it is similar to that of patients without BRAF mutations (4 months ± 0.8 × 4 months ± 0.5, P = .74). The most common AEs reported were elevated liver enzyme levels and dermatological toxicities.

P2, N=49, Completed, Centre Hospitalier Universitaire de Besancon | Active, not recruiting --> Completed | Trial primary completion date: Jul 2023 --> Dec 2023

P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=181, Recruiting, Eisai Inc. | Phase classification: P1b --> P1

P=N/A; Trial primary completion date: Nov 2023 --> Nov 2024

TP53 mutation is a predictor of poor response to veneclax in combination with azacitidine. With the conti-nuation of the combination chemotherapy regimen described above, NRAS mutation is an independent risk factor for DFS in patients. Moreover, the patients with non-negative MRD and NRAS mutations are at high risk of early recurrence.

ORR was 42.5% (95% confidence interval [CI], 23.5-62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

After the analysis of 10827 samples from mCRC patients, we were able to conduct mutation analysis on a total of 10,693 patients. It was shown that there is a high rate (51.1%) of mutation occurrence in KRAS and NRAS genes. These findings indicate that KRAS/NRAS molecular testing is a highly effective approach to select patients who are more likely to respond to anti-EGFR targeted therapy.

KRAS wild-type patient resistance may be related to PIK3CA gene mutations, although this needs further verification in larger cohorts. BRAF mutations may be associated with RNF215 expression in patients with CRC.

We are currently testing new pan-Ras inhibitors to determine if there are distinct responses between our N- and K-ras edited cells, and we are expanding testing to a wider panel of myeloma cell lines containing ras mutations in the context of other genetic abnormalities. Details of gene expression distinctions, pathways, and drug responses that distinguish mutNras and mutKras in myeloma will be presented.

P3, N=673, Active, not recruiting, Ludwig-Maximilians - University of Munich | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2022 --> Nov 2023

To the best of our knowledge, this is the first report of axillary cutaneous metastasis of CRC with microsatellite instability-high and BRAF V600E mutation that could be treated with curative-intent surgery. It is important to recognize the presence of such cases for the accurate diagnosis and treatment of CRC with cutaneous metastasis.