ArticleCancer research communications2026
Early ctDNA Dynamics Predict Response to Mosperafenib in BRAF V600-Mutant Metastatic Colorectal Cancer.
Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
The serine-threonine protein kinase B-RAF (BRAF) V600 mutation confers a poor prognosis in metastatic colorectal cancer (mCRC). Mosperafenib is a novel, paradox-breaking BRAF inhibitor (BRAFi). In this analysis of a phase I study (ISRCTN13713551), we evaluated circulating tumor DNA (ctDNA) as a prognostic and predictive biomarker for mosperafenib monotherapy in BRAF V600-mutant mCRC. We analyzed 49 biomarker-evaluable patients with mCRC (BRAF V600-mutant; 23 BRAFi-naive, and 26 BRAFi-experienced). Plasma samples were collected at baseline and longitudinally. ctDNA levels were quantified using tumor-naive and tumor-informed assays and correlated with RECIST 1.1 response and progression-free survival (PFS). Mutational profiles were assessed to identify resistance mechanisms. Low baseline ctDNA (≤10% tumor fraction) was prognostic for longer median PFS (mPFS; 284 vs. 59 days; HR = 0.32, P = 0.00051). Early ctDNA dynamics were highly predictive; a ≥75% ctDNA reduction at cycle 1 day 15 (C1D15; "molecular response") correlated with longer mPFS (281 vs. 43 days, P < 0.0001). This molecular response occurred in all BRAFi-naive patients versus 48% of BRAFi-experienced patients. Preexisting MAPK pathway resistance mutations were prevalent and prognostic for poor outcomes in the BRAFi-experienced cohort (HR = 3.5, P = 0.003), whereas BRAFi-naive patients acquired these at progression. ctDNA is a powerful biomarker for mosperafenib-treated BRAF V600-mutated mCRC. Low baseline ctDNA is highly prognostic, whereas an early, deep molecular response at C1D15 predicts durable benefit. This response is largely confined to BRAFi-naive patients, as preexisting MAPK pathway alterations in BRAFi-experienced patients correlate with lack of response. These findings support using early ctDNA dynamics as an efficacy endpoint in future trials. SIGNIFICANCE: This study in BRAF V600-mutant mCRC treated with mosperafenib confirms ctDNA's translational utility. Low baseline ctDNA associated with longer PFS and an early deep molecular response predicted durable clinical benefit, supporting its use as an early efficacy endpoint. In addition, ctDNA monitoring enables identification of resistance mechanisms.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.