Mektovi (binimetinib) / Ono Pharmaceutical, Pierre Fabre, Pfizer, Medison - 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

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

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

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

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

Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E. (PubMed, Clin Colorectal Cancer) - "Per DLT criteria, binimetinib + pembrolizumab (cohort A) was tolerable, binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, oxaliplatin (cohort C) did not qualify for binimetinib dose escalation to 45 mg, and binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, irinotecan (cohort E) required binimetinib dose reduction from 45 to 30 mg. No new safety findings were observed across cohorts. There was no apparent additive efficacy when binimetinib + pembrolizumab was added to chemotherapy. Data did not support continued enrollment in cohorts C and E."

Journal • Metastases • Colorectal Cancer • Gastrointestinal Cancer • 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

Real-world outcomes of encorafenib, cetuximab ± binimetinib for BRAF‑mutated metastatic colorectal cancer: The BEETS (JACCRO CC‑18) study. (PubMed, Oncologist) - P=N/A | "In real-world clinical practice, triplet and doublet therapies showed comparable survival outcomes, consistent with the BEACON trial. Triplet therapy may provide potential clinical benefit in patients with poor PFs."

Journal • Real-world evidence • Colorectal Cancer • Oncology • Solid Tumor • BRAF • CRP

A randomized phase 2 trial of encorafenib + binimetinib + nivolumab vs ipilimumab + nivolumab in BRAFV600-mutant melanoma brain metastases: SWOG S2000 (NCT04511013). (ASCO 2025) - P2 | "Steroids up to 8 mg of dexamethasone/day (or equivalent), leptomeningeal spread, and prior local therapy (radiation or surgery) for MBM were permitted, if there was at least one measurable, progressing MBM ≥ 0.5 cm. S2000 is the first randomized trial in patients with symptomatic melanoma brain metastases. A first-line triplet regimen of enco/bini/nivo demonstrated a statistically significant improvement in PFS as compared to ipi/nivo, with a HR of 0.51. Both regimens also had toxicity rates consistent with their known profiles."

Clinical • IO biomarker • Late-breaking abstract • P2 data • Melanoma • Oncology • Solid Tumor

Pembrolizumab in combination with binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer. (PubMed, Clin Cancer Res) - "Pembrolizumab and binimetinib at 30 mg are safe with manageable toxicities. Promising activity was observed in patients without liver metastases. Future larger clinical trials are warranted to further evaluate the efficacy of this chemotherapy-free combination."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • MAPK1 • PD-L1

COLUMBUS 5-Year Update: A Randomized, Open-Label, Phase III Trial of Encorafenib Plus Binimetinib Versus Vemurafenib or Encorafenib in Patients With BRAF V600-Mutant Melanoma. (PubMed, J Clin Oncol) - P3 | "In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with BRAF V600-mutant melanoma."

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

STARBOARD: A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma (clinicaltrials.gov) - P3 | N=257 | Active, not recruiting | Sponsor: Pfizer | Trial primary completion date: Jan 2026 ➔ Oct 2026

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

A first-in-human, phase 1 study of the SHP2 inhibitor PF-07284892 as monotherapy and in combination with different targeted therapies in oncogene-driven, treatment-resistant solid tumors. (ASCO 2023) - P1 | "In the absence of dose limiting toxicity (DLT), matched targeted therapy (lorlatinib for ALK/ROS1 fusion+ cancers, encorafenib + cetuximab for BRAFV600E colorectal cancers, and binimetinib for MAPK-mutant cancers) could be added after 6 weeks of monotherapy at the discretion of the investigator. PF-07284892 was generally well tolerated alone and in combination with rational targeted therapies. This study design enabled combination therapy rescue of disease progression on PF-07284892 monotherapy with 3 pts achieving confirmed PR. Clinical trial information: NCT04800822."

Combination therapy • Monotherapy • P1 data • Anemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • ALK • ROS1

Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. (PubMed, Nat Med) - P3 | "The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. These findings support treatment with Enco+Cetux±Bini for patients with BRAF-V600E-mutant mCRC and provide insights into the biology of response and resistance to MAPK-pathway-targeted therapy. ClinicalTrials.gov registration: NCT02928224."

Journal • Metastases • P3 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • MAP2K1 • MET • TP53

Phase II study SECOMBIT (sequential combo immuno and target therapy study): 4-years OS data and preliminary biomarkers evaluation (ESMO 2022) - P2 | "We used the combination of encorafenib/binimetinib (E+B) as targeted therapy (T-T) and the combination of ipilimumab/nivolumab (I+N) as immunotherapy (I-O). JAK mutations are associated with long term OS. Further biomarkers evaluations are ongoing."

Biomarker • IO biomarker • Late-breaking abstract • P2 data • Melanoma • Oncology • Solid Tumor • CXCL5 • IFNG

Evaluating age as a factor for survival and quality of life in patients with BRAF V600E-mutant metastatic colorectal cancer treated with encorafenib + cetuximab ± binimetinib: subanalysis of BEACON CRC (ESMO-GI 2022) - "Methods BEACON CRC was a randomized, open-label, phase 3 study comparing enco+cetux±bini and investigator's choice of irinotecan+cetux or FOLFIRI+cetux (control) in patients with previously treated BRAF V600E-mutant mCRC...This subanalysis is limited by the low number of patients. Further analyses are warranted to compare these age groups when treated with targeted therapies for mCRC."

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

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial. (PubMed, Nat Commun) - P2 | "BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy."

Biomarker • IO biomarker • Journal • Metastases • P2 data • Melanoma • Oncology • Solid Tumor • BRAF • IFNG

Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial. (PubMed, J Clin Oncol) - P2 | "Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with BRAFV600-mutant melanoma."

IO biomarker • Journal • P2 data • Melanoma • Oncology • Solid Tumor • BRAF

A phase 1 study of the BET inhibitor ZEN003694 in combination with the MEK1/2 inhibitor binimetinib in solid tumors with RAS pathway alterations and triple-negative breast cancer (NCI number 10449). (ASCO 2024) - "Prior therapy with BET, RAF, MEK, or ERK inhibitor is not permitted. This study is currently ongoing in dose escalation."

Combination therapy • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRAF • ER • HER-2 • HRAS • KRAS • NF1 • NRAS • PGR

Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma. (PubMed, NEJM Evid) - P2 | "In patients with unresectable metastatic melanoma, the treatment sequence of immune checkpoint inhibition followed by BRAF/MEK inhibitors was associated with longer periods of new brain metastases-free survival than the reverse sequence. A regimen in which immune checkpoint inhibition was sandwiched between BRAF/MEK inhibition also appeared to be protective against brain metastases. (ClinicalTrials.gov number NCT02631447.)."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor

Baseline circulating tumor DNA (ctDNA) and the efficacy of staged combination with encorafenib + binimetinib + cetuximab following encorafenib + cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer from BAYONET trial. (ESMO 2026) - No abstract available

Circulating tumor DNA • Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • BRAF