P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Outcomes following progression on chemotherapy and MAPK-targeted therapy with Encorafenib plus Cetuximab remain poor, highlighting an unmet need for effective later-line treatments. We discuss the mechanistic framework by which a subset of BRAFV600E-mutant MSS mCRC may respond to immune checkpoint inhibition through an inflamed immune microenvironment driven by constitutive MAPK signalling. This case illustrates the interplay between tumour-agnostic biomarkers such as TMB-high and tumour-specific context, and highlights the value of longitudinal genomic profiling, including ctDNA, to identify resistance mechanisms and guide treatment selection.

Although the TACE+D+C group exhibited immune-related adverse events (irAEs) (e.g., hypothyroidism and reactive cutaneous capillary endothelial proliferation), no significant differences were observed between the two groups in drug-related TRAEs, TRAEs after TACE, or Grade 3 TRAEs. The TACE+D+C group significantly improves ORR, PFS and OS in uHCC patients with a comparable safety profile to the TACE+D group, while the single-center retrospective design limits generalizability, warranting prospective studies.

P1/2, N=15, Terminated, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | N=42 --> 15 | Recruiting --> Terminated; Due to R&D strategy adjustments; no safety issues involved.

P2, N=25, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Active, not recruiting --> Recruiting

P2, N=25, Not yet recruiting, Vall d'Hebron Institute of Oncology

P4, N=46, Recruiting, Pfizer | N=71 --> 46

Avutometinib plus defactinib represents a promising targeted therapeutic strategy for recurrent LGSOC, particularly in patients with KRAS-mutant tumors. If confirmed in phase III trials, this combination may establish a molecularly informed disease-specific treatment paradigm with the potential for more durable disease control than existing therapies.

Building on these findings, we investigated the therapeutic benefit of combining the EGFR inhibitor erlotinib with the novel pan-RAF inhibitor LXH-254. hese results contrast with previous reports of efficacy from monotherapies in xenograft models, highlighting the limitations of current preclinical approaches. Our findings underscore the need to develop more effective pathway-targeted inhibitors, and preclinical models that predict clinical outcomes more accurately.

P2, N=32, Recruiting, Fujian Cancer Hospital; Fujian Cancer Hospital

This study investigates the synergistic effects of capivasertib, an Akt pathway inhibitor, in combination with B-Raf inhibitors (vemurafenib and encorafenib) in B-Raf-mutated melanoma models. Systemic toxicity analyses revealed no significant changes in body weight or serum markers of pancreatic, kidney, or liver function. These findings establish capivasertib and B-Raf inhibitor combinations as a safe and effective strategy for overcoming resistance B-Raf-mutated melanoma, providing new insights into the potential of dual pathway targeting.

P4, N=0, Withdrawn, SRH Wald-Klinikum Gera GmbH | N=101 --> 0 | Not yet recruiting --> Withdrawn