Mektovi (binimetinib)

P1/2, N=341, Recruiting, IDEAYA Biosciences | Trial completion date: May 2025 --> Mar 2027 | Trial primary completion date: Oct 2024 --> Dec 2026

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

P2, N=24, Active, not recruiting, Providence Health & Services | Recruiting --> Active, not recruiting | N=40 --> 24

No abstract available

P3, N=921, Completed, Pfizer | Active, not recruiting --> Completed

The STARBOARD SLI showed that safety across the cohorts was generally comparable to the known safety profile of each agent. The standard dose regimen of COMBO450 plus pembrolizumab was chosen as the RP3D.

P2, N=98, Active, not recruiting, Pfizer | Trial completion date: Dec 2024 --> Oct 2025

P1, N=156, Recruiting, Pfizer | Trial completion date: Feb 2029 --> Nov 2027 | Trial primary completion date: Aug 2027 --> May 2026

P1, N=53, Terminated, Pfizer | Trial completion date: Nov 2025 --> Jun 2024 | Active, not recruiting --> Terminated; The study was prematurely discontinued due to strategic reasons, not major safety concerns, futility, or requests from any regulatory authorities

P1, N=116, Completed, Merck Sharp & Dohme LLC | Phase classification: P1b --> P1

P2, N=119, Recruiting, Intergroupe Francophone de Cancerologie Thoracique | Trial primary completion date: Sep 2024 --> Dec 2024

The BRAF V600E mutation has been identified in a subset of malignant GT, highlighting a promising therapeutic target. Here, we report the impressive clinical and morpho-metabolic response of a metastatic BRAF V600E-mutated glomangiosarcoma after treatment with encorafenib and binimetinib.

P2, N=52, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=56, Completed, Pfizer | Active, not recruiting --> Completed

Through a comprehensive screening process employing in silico drug design methods, this study successfully identified five potential human anticancer drug candidates targeting the beta-catenin protein. These findings offer a foundation for further experimental validation and development towards the treatment of EC.

The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. These findings support treatment with Enco+Cetux±Bini for patients with BRAF-V600E-mutant mCRC and provide insights into the biology of response and resistance to MAPK-pathway-targeted therapy. ClinicalTrials.gov registration: NCT02928224.

The combination therapy of binimetinib, encorafenib, and cetuximab ("triplet regimen") was approved in Japan in November 2020 for the second-line treatment of BRAF V600E mutation-positive colorectal cancer. Hepatic failure occurred in 45.9% (222/484) of the patients within three months, but no specific timing of onset was reported. Since it is important to disseminate novel adverse events to the public, we report the results of this study based on a literature review.

P2, N=53, Completed, University of Colorado, Denver | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Feb 2024

P2, N=38, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=150 --> 38

The study concluded that significant cardiotoxicity occurred in 6% of cases, mostly asymptomatic and reversible, and suggests that monitoring LVEF could potentially be reduced after 6-9 months if no early signs of cardiotoxicity are detected. This provides valuable insights into the cardiac safety of these treatments in real-world settings.

This real-world study showed that in patients with BRAF V600E-mutated mCRC treated with encorafenib/cetuximab +/- binimetinib, efficacy and safety data confirm those reported in the BEACON registration trial. The main poor prognostic factors for this treatment are synchronous metastases and ECOG-PS >1.

The method assessed FTB and BTB interaction potential in combination therapy at 5 mg/kg. The findings provide essential pharmacokinetics insights for future clinical trials.

Ramalingam and Carlisle discuss the incidence and pathophysiology of BRAF V600E-mutant metastatic non-small cell lung cancer and current treatment options. The podcast provides an overview of the data from the recent Pfizer-sponsored phase 2 PHAROS (NCT03915951) study, which were the basis for the recent US Food and Drug Administration approval of encorafenib plus binimetinib for BRAF V600E-mutant metastatic non-small cell lung cancer.

Our results show that BRAFm dMMR/MSI-H mCRC patients benefit from BRAFi+EGFRi+/-MEKi after progression under ICIs. Despite lower ORR and DCR, the outcome is not different from that observed in pMMR/MSS BRAFm CRC and is in line with the results of the BEACON registration trial.

P2, N=102, Completed, Academic and Community Cancer Research United | Trial completion date: Apr 2024 --> Jul 2024 | Active, not recruiting --> Completed

P2, N=25, Recruiting, University of California, San Francisco | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Jul 2024 --> Jul 2025

P1, N=42, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.

P2, N=98, Active, not recruiting, Pfizer | Trial completion date: Oct 2024 --> Dec 2024

P1, N=50, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2027 --> Jan 2026 | Trial primary completion date: Jan 2026 --> Jan 2025

ERK1/2 (ulixertinib and SCH772984), MEK1/2 (binimetinib), and PI3K (pictilisib) inhibitors inhibited growth of RRAS Q87L or RRAS2 Q72L cells more potently than cells expressing wildtype proteins. Oncogenic R RAS/RRAS2 mutations were detected in LUAD at a rate similar to some other well-characterized lung cancer drivers, such as HRAS/NRAS hotspot mutations or NRG1 fusions. Our study supports the inclusion of RRAS /RRAS2 into routine molecular diagnostic protocols for precision oncology and clinical development of pan-RAS inhibitors, such as RMC-6236, for patients with these driver mutations in order to fully realize the potential benefit of RAS-targeted therapies.

Treatment was well tolerated with manageable toxicities, with quality of life and cognitive function maintained throughout treatment. Adding encorafenib/binimetinib to immunotherapy and temozolomide conferred favorable and lasting efficacy for our BRAF V600E -mutant glioblastoma patient, justifying future studies.

In newly diagnosed advanced GIST, ctDNA detection rate of the GIST genotype was low and inversely correlated with duration of rx exposure. However, ctDNA responses proceed radiographic responses, which may be further exploited for non-invasive monitoring of rx response and emerging therapeutic resistance mutations.

P3, N=257, Active, not recruiting, Pfizer | N=189 --> 257

Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.

P2, N=28, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

P1/2, N=34, Active, not recruiting, Pfizer | Trial completion date: Jun 2024 --> Oct 2024

P2, N=70, Recruiting, Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD) | Not yet recruiting --> Recruiting

After 5 years of binimetinib treatment, lung metastases had regrown, and treatment was switched to the oral multikinase inhibitor lenvatinib. This case demonstrates the potential of MEK inhibitor monotherapy as an alternative treatment for BRAF mutation-positive papillary thyroid carcinoma.

P1, N=38, Terminated, Taiho Oncology, Inc. | Phase classification: P1b/2 --> P1

These results highlight that additional targeted DNA NGS in chemotherapy-resistant translocation-associated sarcomas may reveal actionable oncogenic drivers occurring as secondary genetic events during disease progression.

In Japan, encorafenib, binimetinib, and cetuximab triple therapy is a new BRAF targeting regimen approved in 2020. We report this clinical course in hopes of eventually achieving better outcomes for patients with this aggressive disease.