- |||||||||| Review, Journal: RAF and MEK Inhibitors in Non-Small Cell Lung Cancer. (Pubmed Central) - May 11, 2024
New RAF and MEK inhibitors, with distinct biochemical characteristics, are in preclinical and clinical development. In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
P2 data, Journal, IO biomarker: POLARIS: A phase 2 trial of encorafenib plus binimetinib evaluating high-dose and standard-dose regimens in patients with BRAF V600-mutant melanoma with brain metastasis. (Pubmed Central) - May 10, 2024
P2
In this review, we aim to provide valuable insights into the current state of RAF and MEK inhibition in the management of NSCLC, fostering a deeper understanding of the potential impact on patient outcomes. Repeated encorafenib 300
- |||||||||| Retrospective data, Journal, Real-world evidence, IO biomarker, Real-world effectiveness, Real-world, Metastases: Real-world efficacy and safety of BRAF-targeted therapy for patients with advanced melanoma: A single-center retrospective study in Japan. (Pubmed Central) - May 8, 2024
As a prognostic factor, performance status was associated with progression-free survival, and performance status, serum lactate dehydrogenase level, and dose interruption were associated with overall survival in the multivariate analysis. Real-world data on targeted therapy for patients with melanoma in Japan suggest that both dabrafenib?+?trametinib and encorafenib?+?binimetinib show similar efficacy and safety in Asian and White patients.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Journal, Metastases: Dramatic response to encorafenib plus binimetinib in a patient with leukemoid reaction from metastatic melanoma. (Pubmed Central) - May 6, 2024
BRAF gene mutational analysis represents the gold standard in patients with inoperable or metastatic melanoma as the possible presence of target mutations allows the use of the combination treatment with BRAF and MEK inhibitors. In this article, the case of a young woman with BRAF V600E mutated metastatic melanoma associated with PLR who received encorafenib and binimetinib is presented and discussed, with a focus on the relevant treatment response.
- |||||||||| Journal, Metastases: Advanced melanoma with low-burden and low-risk disease: a clinical case. (Pubmed Central) - May 6, 2024
Patients with low tumor burden and low-risk disease (i.e., with normal LDH levels), having higher survival rates and probability of good outcome to systemic therapy, represent a challenge for the clinician, deserving the attempt to reach long-term complete responses. The following case report is quite representative of the above-mentioned clinical situation.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Pharmacist-tailored monitoring for patients initiating encorafenib and binimetinib combination therapy () - Apr 9, 2024 - Abstract #AMCP2024AMCP_37;
This study supports the recommendation to follow up with patients 7-14 days after oral anticancer medi- cation initiation. More studies are needed to evaluate the benefit of increased pharmacist monitoring after the first 2 weeks of therapy.
- |||||||||| tinlorafenib (PF-07284890) / Pfizer
Trial completion date, Trial termination, Trial primary completion date: A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement (clinicaltrials.gov) - Apr 4, 2024
P1, N=65, Terminated,
Trial completion date: Nov 2023 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2023 --> Mar 2024; Pfizer has made an internal business decision to not continue further development of PF-07284890. This decision was not due to major safety concerns or requests from any regulatory authorities.
- |||||||||| PF-07284892 / Pfizer
Enrollment change, Combination therapy, Metastases: PF-07284892 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - Apr 4, 2024
P1, N=53, Active, not recruiting,
This decision was not due to major safety concerns or requests from any regulatory authorities. N=36 --> 53
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Journal, Metastases: Safety and Efficacy of Encorafenib, Binimetinib, and Cetuximab for BRAFV600E-Mutant Metastatic Colorectal Cancer: Results of the Japanese Expanded Access Program. (Pubmed Central) - Mar 30, 2024
There has been one treatment-related death due to cardiac arrest, and two additional patients have experienced treatment-related Grade 4 adverse events, one to hyponatremia, the other due to increased lipase. The efficacy and safety of the BEACON triplet regimen in Japanese patients with BRAFV600E-mutant mCRC were consistent with those reported in the BEACON CRC trial, supporting its use as a standard treatment for pretreated patients with BRAFV600E-mutant mCRC.
- |||||||||| Trial completion date, Trial primary completion date, Metastases: SU2C ACT3: Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer (clinicaltrials.gov) - Mar 21, 2024
P3, N=400, Recruiting,
The efficacy and safety of the BEACON triplet regimen in Japanese patients with BRAFV600E-mutant mCRC were consistent with those reported in the BEACON CRC trial, supporting its use as a standard treatment for pretreated patients with BRAFV600E-mutant mCRC. Trial completion date: Apr 2026 --> Dec 2027 | Trial primary completion date: Apr 2025 --> Dec 2026
- |||||||||| Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion, Metastases: A Trial of mFOLFIRI With MEK162 in Patients With Advanced RAS (HRAS, NRAS, or KRAS) Positive Metastatic Colorectal Cancers (clinicaltrials.gov) - Mar 21, 2024
P1, N=25, Completed,
Trial completion date: Apr 2026 --> Dec 2027 | Trial primary completion date: Apr 2025 --> Dec 2026 Active, not recruiting --> Completed
- |||||||||| Ibrance (palbociclib) / Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Enrollment closed, Phase classification, Enrollment change, Trial completion date, Combination therapy, Metastases: Study of Palbociclib in Combination With Binimetinib for Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - Mar 18, 2024
P1, N=34, Active, not recruiting,
Active, not recruiting --> Completed Recruiting --> Active, not recruiting | Phase classification: P1/2 --> P1 | N=72 --> 34 | Trial completion date: Mar 2024 --> Jun 2025
- |||||||||| ZEN-3694 / Zenith Capital Corp, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Testing the Combination of the Anticancer Drugs ZEN003694 and Binimetinib in Patients With Advanced/Metastatic or Unresectable Solid Tumors With RAS Alterations and Triple Negative Breast Cancer (clinicaltrials.gov) - Mar 18, 2024
P1, N=42, Recruiting,
Recruiting --> Active, not recruiting | Phase classification: P1/2 --> P1 | N=72 --> 34 | Trial completion date: Mar 2024 --> Jun 2025 Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025
- |||||||||| relatlimab (BMS-986016) / BMS, Ono Pharma, Opdivo (nivolumab) / Ono Pharma, BMS
Cost-Effectiveness Analysis of Nivolumab Plus Relatlimab (NIVO+RELA) Versus Current Standard of Care (SOC) for Patients with Unresectable or Metastatic Melanoma in Canada () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_399;
OBJECTIVES: To evaluate the cost-effectiveness of fixed-dose combination NIVO+RELA versus SOC for unresectable or metastatic melanoma (including immunotherapies [IOs]: NIVO, pembrolizumab [PEMBRO], nivolumab+ipilimumab [NIVO+IPI], IPI, and BRAF/MEK inhibitors: vemurafenib+cobimetinib [VEM+COBI], dabrafenib+trametinib [DAB+TRAM] and encorafenib+binimetinib [ENCO+BINI]) from a healthcare payer perspective in Canada... NIVO+RELA is expected to be a life-extending and cost-effective new therapy compared to SOC treatments for unresectable or metastatic melanoma in Canada.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial primary completion date, Combination therapy, Metastases: ENCO-BRAF: ENCOrafenib With Binimetinib in bRAF NSCLC (clinicaltrials.gov) - Mar 7, 2024
P2, N=119, Recruiting,
NIVO+RELA is expected to be a life-extending and cost-effective new therapy compared to SOC treatments for unresectable or metastatic melanoma in Canada. Trial primary completion date: Feb 2024 --> Sep 2024
- |||||||||| bocodepsin (OKI-179) / OnKure, Pfizer
Enrollment closed, Phase classification, Enrollment change, Metastases: NAUTILUS: OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2) (clinicaltrials.gov) - Mar 6, 2024
P1/2, N=36, Active, not recruiting,
Trial primary completion date: Feb 2024 --> Sep 2024 Recruiting --> Active, not recruiting | Phase classification: P1b --> P1/2 | N=73 --> 36
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Journal: Response rate and molecular correlates to encorafenib and binimetinib in BRAF-V600E mutant high-grade glioma. (Pubmed Central) - Mar 6, 2024
P2
Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion date, Trial termination, Combination therapy: Study of Binimetinib With Encorafenib in Adults With Recurrent BRAF V600-Mutated HGG (clinicaltrials.gov) - Mar 6, 2024
P2, N=5, Terminated,
Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients. Trial completion date: Jul 2027 --> Oct 2023 | Active, not recruiting --> Terminated; NCI decided to terminate ABTC Consortium due to NCI moving in different direction for Brain Cancer
- |||||||||| batoprotafib (TNO155) / Novartis, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Characterizing mechanisms of BRAF/MEK inhibitor resistance in BRAF V600 mutant colorectal cancer vs. melanoma (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_8091;
We developed cells with acquired resistance to BRAF+MEK inhibitors (Encorafenib+Binimetinib; E+B) by culturing cells in increasing concentrations of drug over several months. Together, these data identify key, actionable drivers of MAPK inhibitor resistance in CRC and highlight Shp2 as a potential therapeutic target for BRAF V600 CRC.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
ALPPL2 is involved in MAPK signal pathway of pancreatic cancer (Section 16) - Mar 5, 2024 - Abstract #AACR2024AACR_7072;
Our study from a panel of 27 pancreatic cancer cell lines showed that there was no correlation between ALPPL2 expression and response to trametinib. Western blot showed that the level of phospho-ERK was reduced in PANC1 and HPAC cells at 6 hours after trametinib treatment.
- |||||||||| plixorafenib (FORE-8394) / Fore Biotherap
Plixorafenib (plixo) synergizes with MEK inhibitors (MEKi) in MAPK pathway inhibition in BRAF V600 and non V600 alterations, with higher potency compared to early generation BRAFi and pan-RAFi (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_6687;
Using ForeSight assay, a unique platform for testing MAPK signaling, we tested the efficacy of plixo and 4 MEKi (trametinib, cobimetinib, binimetinib and mirdametinib) across a cohort 18 BRAF alterations (V600E, 2 class II and 15 fusions) as single agents and in combinations...Furthermore, we compared the potency of a combination of plixo with binimetinib (bini) to that of another BRAFi (vemurafenib) or pan-RAFi's (tovorafenib and lifirafenib) with bini in 2 class I, 3 class II and 7 BRAF fusions using the foresight assay...These results indicate the improved efficacy of plixo + bini combination in inhibiting MAPK signaling and cancer cell proliferation. Overall results support that maximal suppression of the MAPK pathway with plixo is more potent in combination with a MEK inhibitor in BRAF V600 and non-V600 nonclinical models compared to BRAF or pan-RAF combinations.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Zelboraf (vemurafenib) / Roche, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Analysis of biomarker and outcomes data: 7-year update from COLUMBUS (Section 45) - Mar 5, 2024 - Abstract #AACR2024AACR_6456;
P3
Abstract is embargoed at this time. Background: In the randomized, 2-part, phase 3 COLUMBUS study (NCT01909453), encorafenib (enco) + binimetinib (bini)
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion date, Monotherapy, Metastases: COLUMBUS: Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma (clinicaltrials.gov) - Mar 5, 2024
P3, N=922, Active, not recruiting,
Abstract is embargoed at this time. Trial completion date: Nov 2023 --> Mar 2024
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Avastin (bevacizumab) / Roche, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion date, Combination therapy: Study of Pembrolizumab, Binimetinib, and Bevacizumab in Patients With Refractory Colorectal Cancer (clinicaltrials.gov) - Mar 2, 2024
P2, N=53, Active, not recruiting,
Trial completion date: Nov 2023 --> Mar 2024 Trial completion date: Dec 2023 --> Dec 2024
- |||||||||| Koselugo (selumetinib) / Merck (MSD), AstraZeneca, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Cutaneous toxicities of MEK inhibitor use in children: a retrospective study (San Diego Convention Center (Upper Level, Sails Pavilion, Poster Center 2)) - Feb 20, 2024 - Abstract #AAD2024AAD_2015;
Age appears to be associated with increased likelihood of certain cutaneous reactions. Overall, selumetinib was associated with less severe side effects and decreased risk of MEK inhibitor discontinuation.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
P2 data, Journal, Combination therapy, Metastases: A phase II study of encorafenib in combination with binimetinib in patients with metastatic BRAF-mutated thyroid cancer in Japan. (Pubmed Central) - Feb 12, 2024
Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Braf Inhibitor Therapy Associated Inflammatory Arthritis in Patients with Metastatic Cancer: a Case Series () - Feb 8, 2024 - Abstract #CRAAHPA2024CRA_AHPA_111;
Case 1: A 69-year-old female with metastatic melanoma presented with two months of arthralgias in bilateral shoulders, hands, knees, and feet after starting BRAFi/MEKi therapy with encorafenib/binimetinib...Case 2: A 61-year-old male with metastatic colorectal cancer presented with three months of arthralgias after starting BRAFi/EGFRi therapy with encorafenib/cetuximab...She was treated with prednisone 10mg and IA corticosteroid injections to her right wrist, left 3rd flexor tendon sheath, and bilateral knees. Targeted therapy was restarted, and arthritis remained under control as prednisone was tapered.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Enrollment closed, Metastases: STARBOARD: A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma (clinicaltrials.gov) - Feb 6, 2024
P3, N=176, Active, not recruiting,
Updated data including circulating tumor DNA variant allele frequency associated with response and final analysis of primary endpoints will be presented. Recruiting --> Active, not recruiting
- |||||||||| Ibrance (palbociclib) / Pfizer, gedatolisib (PF-05212384) / Celcuity, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Combined inhibition of CDK4/6 and signal transduction: activity beyond ER+ breast cancer (Ballroom 6 DE - Upper Level - Convention Center) - Feb 5, 2024 - Abstract #AACR2024AACR_1213;
The palbociclib-binimetinib combination has recently been incorporated into the NCI Precision Medicine Initiative as part of ComboMATCH, where investigation is ongoing in low-grade serous ovarian cancer, pancreatic cancer, and other RAS-mutant tumors. Such combinations hold substantial promise for extending the use of the CDK4/6 inhibitor drug class beyond ER+ breast cancer.
- |||||||||| Braftovi (encorafenib) / Ono Pharma, Pierre Fabre, Pfizer, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Trial completion, Metastases: ANCHOR-CRC: Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer (clinicaltrials.gov) - Feb 2, 2024
P2, N=95, Completed,
Such combinations hold substantial promise for extending the use of the CDK4/6 inhibitor drug class beyond ER+ breast cancer. Active, not recruiting --> Completed
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