BRAF V600K

P1, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1, N=2, Active, not recruiting, Richard Wu | Recruiting --> Active, not recruiting | N=15 --> 2 | Trial completion date: Dec 2025 --> Dec 2024

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

P3, N=922, Active, not recruiting, Pfizer | Trial completion date: Nov 2023 --> Mar 2024

P1/2, N=33, Recruiting, University of Utah | Not yet recruiting --> Recruiting

P1; Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=58, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

P1, N=71, Suspended, JS InnoPharm, LLC | N=124 --> 71 | Trial primary completion date: Dec 2023 --> Jun 2024

P2, N=68, Suspended, ImmVira Pharma Co. Ltd | Phase classification: P2a --> P2 | Trial completion date: Jan 2026 --> Jan 2027 | Not yet recruiting --> Suspended | Trial primary completion date: Dec 2025 --> Dec 2026

P3, N=176, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1/2, N=33, Not yet recruiting, University of Utah

P1/2, N=78, Recruiting, Peter MacCallum Cancer Centre, Australia | Phase classification: P1b --> P1/2 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=280, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P3, N=240, Recruiting, Pfizer | N=624 --> 240

P1/2; Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Conclusion  This constitutes one of the few reports on comprehensive analysis of molecular alterations underlying melanomas in Indian patients. A larger sample size, with more extensive molecular markers, would yield additional information on the disease manifestation.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Oct 2023 --> Apr 2025

In in vitro and ex vivo settings, the combination therapy was observed to elicit a response; however, it did not amplify the efficacy observed with binimetinib alone, whereas in a patient, the combinational treatment remained ineffective. The preclinical in vivo data showed no increased combinatorial effect. However, the in vivo effect of binimetinib as monotherapy was unexpectedly high in the tested regimen. Nevertheless, binimetinib proved to be advantageous in the treatment of melanoma in vivo and led to high rates of apoptosis in vitro; hence, it still seems to be a good base for combination with other substances in the treatment of patients with NRAS-mutant melanoma.

P1; Trial completion date: Jul 2023 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Dec 2024

R-ISS and RNA-sequencing identify partially overlapping patient populations, with R-ISS missing, e.g., 30% (22/72) of highly proliferative myeloma. RNA-sequencing based assessment of risk and targets for first choice treatment is possible in clinical routine.

This is the largest study to date describing patients treated with dabrafenib plus trametinib in routine clinical practice in Italy between 2018 and 2019. Results highlight the characteristics of the patients treated and their journey, as well as the tolerable safety profile of dabrafenib plus trametinib in a real-world patient population.

P2, N=12, Completed, University of Heidelberg Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Mar 2023 | Trial primary completion date: Dec 2022 --> Mar 2023

P3, N=815, Active, not recruiting, Pierre Fabre Medicament | Recruiting --> Active, not recruiting

P2, N=26, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024 | Recruiting --> Active, not recruiting

P3, N=624, Recruiting, Pfizer | Trial completion date: Feb 2030 --> Jul 2026 | Trial primary completion date: Sep 2024 --> Feb 2025

P2, N=271, Active, not recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2022 --> Nov 2023

Trametinib is FDA-approved for the treatment of adults with advanced melanoma with BRAF V600E or V600K mutations and in children with Ras-mutant solid tumors in combination with dabrafenib...High-risk patients will receive trametinib administered once-daily for 28 days in combination with azacitidine, fludarabine, and cytarabine (aza/FLA) administered daily for five days per cycle...The study is open to accrual at all TACL consortium sites. We acknowledge the TACL Consortium's scientific contribution to and participation in this study, including participating member institutions, investigators, research teams, and the TACL Operations Center.

The Idylla BRAF Mutation Assay is a highly reliable and sensitive platform for detecting BRAF pathogenic variants in codon 600 in malignant melanoma. The test can be performed in less than two hours, significantly improving turnaround time, thus allowing faster time to treatment.

These data support that the tumor likely arose from three separate clonal populations, the BRAF V600E population and the KRAS G12G and KRAS G12C populations, each having distinct molecular pathways to tumorigenesis. Future directions include measuring spatial gene expression patterns of the tumor to correlate with the tumor mapping described above and to further characterize the multiple populations of tumor cells harboring different driver alterations and molecular pathways to tumorigenesis.

P2, N=150, Ongoing, UNICANCER

Patients must have had histologically confirmed locally advanced or metastatic melanoma and had to have received at least one cycle of immunotherapy (single agent nivolumab, pembrolizumab, or combination ipilimumab plus nivolumab). The superior survival observed in the younger patients is possibly related to the higher utilization of combination ICI. Tumor response to immunotherapy is superior in older patients with cutaneous melanoma; however, younger patients may improve their survival by using combination ICI.

Treatment options include plasmapheresis, dialysis, kidney transplantation and administration of the C5 antibody eculizumab...If CMV reactivation was detected, treatment was given with valacyclovir. In the case of cerebral progression, therapy with dabrafenib/trametinib was carried out after cerebral radiation with the BRAF V600K mutation...In this case, autoimmune nephritis, past Covid-19 infection and postoperative condition after laparotomy also come into consideration as summation factors. Interdisciplinary management of serious side effects is crucial for the outcome of affected patients

P2, N=20, Recruiting, Leiden University Medical Center

P2, N=4, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Oct 2023 | Trial primary completion date: Feb 2024 --> Oct 2023

P=N/A, N=3, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Oct 2024 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Jul 2023; low accrual and lack of funds

Encorafenib is a novel kinase inhibitor of BRAF V600E as well as wild-type BRAF and CRAF and has received approval, in combination with binimetinib, to treat BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma or in combination with cetuximab to treat BRAF V600E mutation-positive colorectal cancer. Oral absorption was estimated from the radioactive dose recovered in the urine (47.2%) and the total radioactive dose recovered in the feces as metabolites (39%). Based on these values and the assumptions that encorafenib and its metabolites are stable in feces, the fraction of oral absorption was estimated to be at least ~86%.

P1; Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

Compared to LDH and S100B, ctDNA levels in stage I to III MM display superior sensitivity to detect MRD and could complement regular FU in predicting tumor progression. In the currently initiated prospective study part (MeLB), we will evaluate ctDNA as marker for MRD identifying patients with stage IIB to III MM at risk for relapse. We will include 50 patients followed for two years quarterly and compare standard singleplex with novel multiplex ddPCR strategies (parallel detection of up to 10 ctDNA mutations) and a custom design NGS panel.

P1, N=124, Suspended, JS InnoPharm, LLC | Recruiting --> Suspended | Trial primary completion date: May 2023 --> Dec 2023

P2, N=95, Active, not recruiting, Fondazione Melanoma Onlus | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2022 --> Dec 2023

Here we provide an overview of the rationale for combining BRAF and MEK inhibitors for the treatment of melanoma, long-term safety results from COLUMBUS, and guidance on managing the most common adverse events associated with this combination based on clinical experience. Proactive and appropriate management of adverse events can allow for longer treatment durations and may result in better treatment outcomes.

Real-world adjuvant systemic therapy aligns with clinical trial practice. Recurrence rates remain high despite treatment, and long-term toxicities, including endocrinopathies and chronic inflammatory conditions, are not uncommon.