NRAS wild-type

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.

P3, N=480, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jan 2024 --> Sep 2024

These data highlight the impact of combination anti-CTL4/ anti-PD1 immunotherapy in decreasing BM incidence in melanoma.

P1, N=325, Active, not recruiting, Exelixis | Recruiting --> Active, not recruiting | N=921 --> 325

Our study suggests that adjuvant toripalimab and pembrolizumab therapy have comparable efficacies in patients with AM and are both well tolerated. Adjuvant monotherapy with PD-1 inhibitors may not be appropriate for AM with NRAS mutations.

In this older and very high-risk population of pts with AML, an entirely oral regimen consisting of ASTX727 and venetoclax was effective and tolerable.

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.

Primary limitations include the total quantity of single cells and breadth of available genomic subtypes plus inherent noisiness of the applied methodologies. Nonetheless, these findings nominate novel, testable therapeutic targets.

P1, N=42, Recruiting, Roswell Park Cancer Institute | Not yet recruiting --> Recruiting

P2, N=34, Recruiting, National Cancer Institute, Naples | Trial completion date: Mar 2023 --> Jan 2024 | Trial primary completion date: Mar 2022 --> Jan 2024

A literature review reported no renal adverse effects associated with pan-RAF agents.Belvarafenib is a novel agent; further research and time are required to determine its adverse effects incidence. However, clinicians must remain vigilant about the potential kidney adverse effects of this agent and consider a kidney biopsy to assess AIN in patients whose AKI does not respond promptly to discontinuing Belvarafenib and supportive care.

The R151C and D294H RHC variants displayed impaired cAMP signaling, intracellular stability similar to the wildtype, triggered ERK1/2 activation as effectively as the wildtype, and afforded partial protection against oxidative DNA damage, although less efficiently than the wildtype. Therefore, common melanoma-associated MC1R variants display biased signaling and significant genoprotective activity.

P1, N=5, Terminated, Fate Therapeutics | Trial completion date: Apr 2027 --> Aug 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Aug 2023; This study was terminated by the Sponsor.

P3, N=7, Terminated, Institut de Recherches Internationales Servier | N=500 --> 7 | Trial completion date: Oct 2026 --> Jun 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2026 --> Jun 2023; Decision based on strategic reasons related to limited development options left in metastatic colorectal cancer.

There were no instances of MSI in 56 non-colorectal tumors carrying ALK, ROS1, RET or NTRK1 rearrangements. An analysis of tyrosine kinase gene translocations is particularly feasible in KRAS/NRAS/BRAF wild-type microsatellite-unstable CRCs, although other categories of tumors with MSI also demonstrate moderate occurrence of these events.