BRAF mutation

P3, N=195, Recruiting, InnoPharmax Inc. | Not yet recruiting --> Recruiting

P1/2, N=53, Recruiting, Iovance Biotherapeutics, Inc. | Trial completion date: Jun 2027 --> Sep 2029 | Trial primary completion date: Jun 2025 --> Sep 2027

Recent developments in personalized medicine, including the introduction of new molecular diagnostic tools and targeted agents, have made considerable progress in the risk stratification and treatment strategies for papillary thyroid carcinoma. The current article reviews molecular mechanisms of activation of MAPK and PI3K/AKT pathways, their interaction, clinicopathological importance, and targeted treatments in papillary thyroid carcinoma.

We further introduce VirtualWSI, a platform for semantic perturbation within an interpretable spatial biomarker atlas. PathPrism provides a scalable and interpretable framework for spatial biomarker discovery.

P2, N=1, Terminated, Genmab | Trial completion date: Jul 2029 --> May 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2027 --> May 2026; Genmab has decided to discontinue further clinical development of acasunlimab following strategic portfolio prioritization. The decision was not related to safety concerns.

Although BRAF-targeted therapies have been positioned within the tumour-agnostic paradigm, the available evidence suggests clinically meaningful activity across multiple non-melanomatous BRAF-mutant tumours that is nevertheless modified by tumour lineage, biological context, and treatment strategy.

BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization...dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC.

Genetic testing of the PMs revealed no mutations in BRAF, KRAS, or NRAS, and no RET rearrangement. The patient's condition was subsequently managed with targeted therapy and immunotherapy, which achieved disease stabilization.

We report a 59-year-old female non-smoker with stage IV EGFR Leu858Arg-mutated lung adenocarcinoma who sequentially received first-line osimertinib (~9 months), second-line osimertinib plus savolitinib for MET amplification (~20 months), third-line platinum-based chemotherapy with local ablative therapy for oligo-progression, and fourth-line docetaxel. This case illustrates that an acquired BRAF fusion may emerge as a potentially targetable bypass alteration in EGFR-mutated MET-amplified NSCLC after progression on combined EGFR-MET inhibition and that the combination of a first-generation EGFR-TKI and a MEK inhibitor can be associated with prolonged systemic disease control. The findings are hypothesis-generating and support the value of CGP at sequential progression points to guide mechanism-based therapy in oncogene-driven NSCLC.

P2/3, N=220, Recruiting, Summit Therapeutics Inc. | Not yet recruiting --> Recruiting

The disease later relapsed as high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-MYC/BCL2), still harbouring the BRAF mutation. Complete remission was achieved with Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisone, but the double-hit lymphoma relapsed 14 months later.This case illustrates sequential transformation from FL to BRAF-mutated HDS with excellent response to BRAF/MEK inhibition, followed by evolution into HGBCL-MYC/BCL2 responding transiently to immunochemotherapy, emphasising the value of repeated histological and molecular reassessment in FL evolution.

BRAF mutation is presumed to be associated with tumor progression and may predict growth of PTMC. Genetic testing including BRAF testing may help distinguishing rapid-growing thyroid cancer.