Braftovi (encorafenib) / Ono Pharmaceutical, Pierre Fabre, Pfizer, Medison, Nerviano Medical Sciences - LARVOL DELTA

TRIDENTE: A phase II study of rechallenge with encorafenib (ENCO), binimetinib (BINI), and cetuximab (CET) in BRAF V600E-mutant metastatic colorectal cancer (mCRC) (ESMO 2026) - No abstract available

Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF

First-line (1L) encorafenib + cetuximab + mFOLFOX6 in East Asian patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC): Results from the phase III BREAKWATER study (ESMO Asia 2025) - P3 | "Background: The randomized phase 3 BREAKWATER study (NCT04607421) demonstrated statistically significant and clinically meaningful improvements in ORR by blinded independent central review (BICR), PFS by BICR, and OS with encorafenib + cetuximab (EC) + mFOLFOX6 vs control (chemotherapy ± bevacizumab) in 1L BRAF V600E-mutant mCRC (Kopetz, Nat Med 2025; Elez, N Engl J Med 2025)... Consistent with the global study results, East Asian pts with untreated BRAF V600E-mutant mCRC attained clinically significantly improved ORR, PFS, and OS with EC+mFOLFOX6 vs control therapy. The treatment safety profiles in East Asian pts were consistent with those observed in the overall population and as expected for each agent."

Clinical • Metastases • P3 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Updated results from ERAS-007 plus encorafenib and cetuximab (EC) in patients (pts) with EC-naïve metastatic BRAF V600E colorectal cancer (CRC) in the phase 1b/2 HERKULES-3 study. (ASCO 2024) - P1/2 | "ERAS-007 100 mg BID-QW in combination with EC was safe and well tolerated with preliminary evidence of promising clinical activity. These results support continued evaluation of this combination in EC naïve pts with BRAF V600E CRC."

Clinical • Metastases • P1/2 data • Anemia • Colorectal Cancer • Constipation • Dermatitis • Dermatology • Fatigue • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Immunology • Oncology • Pain • Respiratory Diseases • Solid Tumor • BRAF

SEAMARK: Randomized phase 2 study of pembrolizumab + encorafenib + cetuximab versus pembrolizumab alone for first-line treatment of BRAF V600E-mutant and microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC). (ASCO 2022) - P2 | "Secondary endpoints include safety and tolerability, overall survival, objective response rate, duration of response, and quality of life. Enrollment will begin in April 2022."

Clinical • IO biomarker • Mismatch repair • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • BRAF • MSI

SU2C ACT3: Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer (clinicaltrials.gov) - P3 | N=400 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Colon Adenocarcinoma • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF

BREAKWATER safety lead-in (SLI): Encorafenib (E) + cetuximab (C) + chemotherapy for BRAFV600E metastatic colorectal cancer (mCRC). (ASCO-GI 2023) - P2, P3 | "In the phase 2 ANCHOR study (NCT03693170), mPFS was 5.8 mo and ORR was 48% for 1L EC + binimetinib in BRAFV600E mCRC...Pts received E 300 mg daily + C 500 mg/m2 every 2 weeks (Q2W) + either mFOLFOX6 Q2W (n=27) or FOLFIRI Q2W (n=30) in 28-day cycles until disease progression or unacceptable toxicity...Expected conclusions will be included in the final abstract. Clinical trial information: NCT04607421."

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI

Adjuvant Therapy Based on Pathologic Response After Neoadjuvant Encorafenib Binimetinib in Melanoma (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jul 2027 ➔ Apr 2027 | Trial primary completion date: Jul 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Encorafenib plus binimetinib in patients (pts) with previously untreated BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC): An open-label, multicenter phase II trial (IFCT-1904 ENCO-BRAF) (ESMO 2024) - P2 | "Current ESMO guidelines recommend dabrafenib plus trametinib as preferred first-line treatment options or as subsequent treatment for BRAFV600E-mutant advanced NSCLC. In this phase 2 trial with treatment-naïve BRAFV600E-mutant advanced NSCLC, encorafenib plus binimetinib demonstrated robust clinical activity. The safety profile was manageable and consistent with previous studies in lung cancer and melanoma."

Clinical • Metastases • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. (PubMed, Nat Med) - P3 | "BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421 ."

Journal • P3 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Neoadjuvant encorafenib and cetuximab in locally advanced BRAF V600E colon cancer: first safety and feasibility results of the proof-of-concept NEORAF trial (ESMO 2026) - No abstract available

Clinical • Metastases • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Updated efficacy and safety from the phase II PHAROS study of encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC) (ESMO 2024) - P2 | "After an additional 18 mo of follow-up, enco+bini showed prolonged efficacy, especially in treatment-naïve pts, with a manageable safety profile in pts with BRAF V600E-mutant mNSCLC."

Clinical • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • BRAF

Efficacy and safety of encorafenib (enco) plus binimetinib (bini) in patients with BRAF V600E-mutant (BRAFV600E) metastatic non-small cell lung cancer (NSCLC) from the phase 2 PHAROS study. (ASCO 2023) - P2 | "Background: The combination of dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor, is a current standard of care for patients (pts) with BRAFV600E NSCLC. The combination of enco+bini showed meaningful clinical benefit in treatment-naive and previously treated pts with BRAFV600E metastatic NSCLC. The safety profile of enco+bini was generally consistent with that established for pts with BRAFV600E/K melanoma. ClinicalTrials.gov: NCT03915951."

Clinical • IO biomarker • Metastases • P2 data • Cerebral Hemorrhage • CNS Disorders • Fatigue • Hematological Disorders • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • CDKN2A • CSF1R • KMT2D • MLL2 • SETD2 • SMAD4 • SMARCA4 • TP53

Eruptive Melanocytic Nevi Associated With Encorafenib and Cetuximab Therapy in Two Patients With BRAF V600E-Mutated Colorectal Cancer. (PubMed, J Dermatol) - No abstract available

Journal • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study). (PubMed, Neuro Oncol) - "Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response."

Journal • P2 data • Melanoma • Oncology • Solid Tumor

Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial. (PubMed, J Clin Oncol) - "COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety."

Journal • P3 data • Melanoma • Oncology • Solid Tumor • BRAF

Colorectal neuroendocrine neoplasm organoids reveal the potential therapeutic value of targeting BRAF mutations. (PubMed, J Endocr Soc) - "In vitro pharmacological assays demonstrated that BRAF inhibitors (IC50: dabrafenib = 3.766 μM; encorafenib = 5.454 μM) and MEK inhibitors (IC50: trametinib = 6.602 nM; binimetinib = 0.749 μM) effectively inhibited the proliferation of organoids harboring the BRAF mutation. PDOX experiments revealed that continuous oral administration of dabrafenib and trametinib resulted in a tumor growth inhibition of 66.27%. Organoids represent reliable preclinical models for drug screening in colorectal NENs, and BRAF mutations may constitute a promising therapeutic target for patients with colorectal NENs."

Journal • Colorectal Cancer • Endocrine Cancer • Oncology • Solid Tumor • BRAF • NCAM1 • SSTR • SSTR2 • SYP

Health-related Quality of Life with Encorafenib plus Binimetinib for BRAFV600E Thyroid Cancer. (PubMed, Eur Thyroid J) - "Combination therapy of encorafenib plus binimetinib for unresectable BRAF V600-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL."

HEOR • Journal • Anorexia • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Pain • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF

Encorafenib plus binimetinib in NRAS-mutant melanoma after immunotherapy progression: a real-world descriptive case series (ESMO 2026) - No abstract available

Clinical • IO biomarker • Real-world • Real-world evidence • Melanoma • Oncology • Solid Tumor

A phase II clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma. (PubMed, Blood) - P2 | "This prospective single-arm, open-label, multicenter phase II trial assessed the efficacy and safety of combined BRAF/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation (ClinicalTrials.gov identifier: NCT02834364). Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF/MEK inhibition is highly effective in patients with BRAFV600E mutated RRMM and represents a successful targeted precision medicine approach in this disease."

Journal • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Encorafenib plus binimetinib in patients (pts) with BRAFV600E-mutant advanced non-small cell lung cancer: updated efficacy and safety results from the IFCT-1904 ENCO-BRAF phase 2 trial (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF

STARBOARD Phase 3: A randomized, double-blind study of first-line (1L) encorafenib (enco), binimetinib (bini), and pembrolizumab (pembro) vs placebo (pbo) and pembro for unresectable locally advanced or metastatic BRAF V600-mutant melanoma (ESMO 2026) - No abstract available

Clinical • Metastases • P3 data • Melanoma • Oncology • Solid Tumor • BRAF

Encorafenib + cetuximab (EC) + FOLFIRI for BRAF V600E-mutant metastatic colorectal cancer (mCRC): Updated results from the BREAKWATER safety lead-in (SLI) (ESMO 2024) - P3 | "Pts received E 300 mg once a day + C 500 mg/m2 intravenously (IV) every 2 weeks (Q2W) + FOLFIRI/mFOLFOX6 IV Q2W in 28-day cycles... EC + FOLFIRI was generally tolerable, with no new safety signals identified. The antitumor activity reported is encouraging. These results support the continued evaluation of EC + chemo in cohort 3."

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF

Synchronous Gray Zone Lymphoma and Colon Adenocarcinoma: A Diagnostic and Therapeutic Challenge (SOHO 2026) - "She completed 5 total cycles, followed by 3 cycles of adjuvant capecitabine for colon adenocarcinoma...Next-generation sequencing identified BRAF V600E and BRCA1 mutations, prompting initiation of FOLFOX, panitumumab, and encorafenib...Clinical approaches range from DLBCL-based regimens like R-CHOP and DA-EPOCH-R to cHLbased regimens, such as ABVD, with emerging roles for brentuximab vedotin and nivolumab...In the setting of a synchronous malignancy, careful chemotherapy sequencing is critical. Tissue-based differentiation between lymphoma progression and secondary cancer recurrence carries direct therapeutic implications and must guide individualized management decisions ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine, BCL6: B-cell lymphoma 6, BRAF: B-Raf proto-oncogene, BRCA1: BRCA1 DNA repair associated, CD: cluster of differentiation, cHL: classical Hodgkin lymphoma, DA-EPOCH-R: dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin,..."

B Cell Lymphoma • Classical Hodgkin Lymphoma • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Oncology • BCL6 • BRAF • BRCA1 • CD20 • CD79A • IRF4 • PAX5 • PTPRC • TNFRSF8

Targeted BRAF /MEK inhibition as a salvage therapy for patients with metastatic melanoma harboring a BRAF L597R mutation: two case reports and review of the literature. (PubMed, Melanoma Res) - "Because of rapid clinical deterioration and disease progression, the treatment was switched to binimetinib in case 1 and binimetinib/encorafenib combination therapy in case 2. These cases illustrate that targeted therapy can induce a rapid response in patients with metastatic melanoma harboring the BRAF L597R mutation while also highlighting the risk of early treatment resistance. This treatment option should be considered, particularly for patients with pronounced symptoms and high tumor burden."

Journal • Melanoma • Oncology • Solid Tumor

Triple-Targeted Therapy With Encorafenib, Binimetinib, and Osimertinib in EGFR-Mutated NSCLC With Acquired BRAF Alteration After Osimertinib: A Single-Center Experience. (PubMed, JTO Clin Res Rep) - "Although case series have reported activity with dabrafenib, trametinib, and osimertinib in metastatic NSCLC, there are no published data on the combination of encorafenib, binimetinib, and osimertinib (E+B+O) in this population. This study presents a novel treatment combination for EGFR-mutant metastatic NSCLC with an acquired BRAF alteration. Larger studies are needed to determine whether E+B+O may be considered in carefully selected patients with close response assessment and monitoring for gastrointestinal toxicity."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR