mosperafenib (RG6344) / Roche - LARVOL DELTA

Mosperafenib, a novel paradox breaker BRAF inhibitor with potent preclinical activity in BRAF mutated colorectal cancer. (PubMed, Mol Cancer Ther) - "The therapeutic benefit of the combination of the first generation BRAFi encorafenib and the EGFR blocking antibody cetuximab in second line metastatic colorectal cancers (CRC) harboring BRAF V600E mutations remains limited and short lived...Additional combination studies of mosperafenib with FOLFOX resulted in tumor regression and superior activity compared to the same combination with encorafenib. Collectively these data provide a strong preclinical rationale for the potentially transformative activity of mosperafenib as monotherapy and as a preferred backbone BRAFi for combinatorial regimen for BRAF mutated CRC."

Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor

Evaluating ctDNA as a predictive biomarker in a phase I clinical trial of mosperafenib in BRAFV600E-mutant colorectal cancer (ESMO 2025) - "Conclusions This study demonstrates that RG6344 exhibits promising clinical efficacy in mCRC patients, including those with prior BRAFi treatment (mPFS = 3.7 months). The findings suggest ctDNA is a robust biomarker for monitoring of on-treatment tumor dynamics and treatment response."

Biomarker • Circulating tumor DNA • Clinical • P1 data • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Sarah Cannon Research Institute to Showcase Cancer Insights at 2025 ASCO Annual Meeting (Businesswire) - "Today, Sarah Cannon Research Institute (SCRI), one of the world’s leading oncology research organizations conducting community-based clinical trials, announced that it will showcase its latest research highlights through more than 155 accepted abstracts and presentations at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago from May 30-June 3, 2025. Over 75 investigators from more than 20 research sites in SCRI’s network are first authors and co-authors on the clinical trial updates featured at the Annual Meeting, including findings from 55 early-phase clinical trials."

Clinical data • Platinum resistant • Biliary Tract Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor

Preliminary safety, pharmacokinetics, and clinical activity of RG6344 in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC). (ASCO 2025) - "RG6344 is well tolerated allowing unprecedented exposure for pERK inhibition and shows promising preliminary single-agent activity."

Clinical • Metastases • PK/PD data • Colorectal Cancer • Dermatology • Fatigue • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • BRAF

The novel brain-penetrant paradox breaker BRAF inhibitor RG6344 manifests exceptional activity in BRAF mutant colorectal cancers (AACR 2025) - "In BRAFi naïve xenograft models (LS411N, HT29) RG6344 as monotherapy outperformed Encorafenib/Cetuximab at all doses tested indicating higher activity of this agent even at doses targeting only IC80 p-ERK inhibition, the same BRAF inhibition levels reached by Encorafenib in CRC approved clinical regimens. RG6344 activity was further strengthened in combination with cetuximab and demonstrated long-lasting responses in PDX models derived from patients that progressed to Encorafenib/Cetuximab therapy supporting the use of RG6344 even in BRAFi experienced patients.Additional combination studies of RG6344 with FOLFOX in BRAFi naive models resulted in tumor regression and dramatic superiority compared to the same combination with Encorafenib.These data collectively provide strong preclinical translational evidence for the potentially transformative activity of RG6344 in BRAF mutated CRC."

Colorectal Cancer • Oncology • Solid Tumor

A phase I study evaluating safety, pharmacokinetics, and clinical activity of the novel, paradox breaker BRAF inhibitor RG6344 in patients with BRAF V600-mutant solid tumors (AACR 2025) - "RG6344 (RO7276389) is a novel brain penetrant paradox breaker BRAFi designed to address the limitations of approved BRAFi. Dose escalation of RG6344, as a single agent and in combination with standard dose of cobimetinib, is being conducted in participants with solid tumors harboring a BRAF V600E mutation up to the protocol specified maximum daily dose. RG6344 is well tolerated allowing unprecedented exposure for pERK inhibition and shows promising preliminary activity."

Clinical • P1 data • PK/PD data • Colorectal Cancer • Melanoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • EGFR