Post by icemandios on Sept 30, 2019 13:37:56 GMT
Pfizer Presents Interim Analysis Results from Phase 3 BEACON CRC Trial of BRAFTOVI® (Encorafenib), MEKTOVI® (Binimetinib) and Cetuximab for the Treatment of BRAFV600E-Mutant Metastatic Colorectal Cancer
- As previously announced, BRAFTOVI combinations showed statistically significant improvements in OS and ORR versus control –
As previously reported, the BRAFTOVI Triplet and Doublet were generally well-tolerated with no unexpected toxicities. Grade 3 or higher adverse events (AEs) were seen in 58%, 50% and 61% of patients in the BRAFTOVI Triplet, Doublet and Control arms, respectively. Discontinuation of therapy due to adverse events was seen in 7%, 8% and 11% of patients in the Triplet, Doublet and Control arms, respectively. The most common Grade 3 or higher AEs seen in patients treated with the BRAFTOVI Triplet were diarrhea (10% vs. 2% in the Doublet arm and 10% in the Control arm), abdominal pain (6% vs. 2% in the Doublet arm and 5% in the Control arm) and nausea (5% vs. Details for the late-breaking oral presentation are below. The abstract can be accessed through the ESMO website: www.esmo.org/Conferences/ESMO-Congress-2019.
Title/Abstract Number
Date/Time (CEST)
Location
(LBA32)
Encorafenib plus cetuximab with or
without binimetinib for BRAF V600E–
mutant metastatic colorectal cancer:
expanded results from a randomized,
3-arm, phase 3 study vs. the choice
of either irinotecan or FOLFIRI plus
cetuximab (BEACON CRC)
Tabernero J
Monday, September 30
8:30-8:45 AM
Barcelona
Auditorium
About Colorectal Cancer
About BEACON CRC
About BRAFTOVI + MEKTOVI
NEW YORK
- Results to be presented during a late-breaking oral session at the 2019 ESMO Congress and simultaneously published in The New England Journal of Medicine –
Pfizer Inc. (NYSE: PFE) today announced detailed results from the interim analysis of the Phase 3 BEACON CRC trial evaluating the combination of BRAFTOVI® (encorafenib), MEKTOVI® (binimetinib), and cetuximab (BRAFTOVI Triplet), in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC), following one or two lines of therapy. The results show significant improvements in overall survival (OS) and objective response rates (ORR) for the BRAFTOVI Triplet and BRAFTOVI Doublet combination (BRAFTOVI and cetuximab), compared to cetuximab plus irinotecan-containing regimens (Control), and provide analysis of the efficacy and safety of the BRAFTOVI Triplet compared to the BRAFTOVI Doublet. These data will be presented today during a late-breaking oral session at the 2019 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain, and simultaneously published online in The New England Journal of Medicine (NEJM). Pfizer intends to submit the results of the BEACON CRC trial for marketing approval in the U.S. in the fourth quarter of 2019. The use of BRAFTOVI, MEKTOVI and cetuximab for the treatment of patients with BRAFV600E-mutant mCRC is investigational and not approved by the FDA.
As previously announced, the BRAFTOVI Triplet showed a median OS of 9.0 months for patients treated with the Triplet, compared to 5.4 months for Control ([HR 0.52, (95% CI 0.39-0.70), p “We are pleased to share these data from the BEACON CRC trial with the oncology community,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “With no approved therapies currently indicated specifically for BRAF-mutant mCRC, we believe that the evidence so far shows encouraging potential for the BRAFTOVI Triplet to make a meaningful impact on the lives of those living with this disease.”
The study also showed improvements in secondary efficacy endpoints. As previously announced, the BRAFTOVI Doublet showed a statistically significant improvement in OS (median 8.4 months vs. 5.4 months,
) compared to Control. Additional analysis showed depth of responses in favor of the BRAFTOVI Triplet.
) compared to Control. Additional analysis showed depth of responses in favor of the BRAFTOVI Triplet.
“The BEACON CRC trial results show meaningful improvements compared to an available standard of care for patients with BRAFV600E-mutant mCRC," said Scott Kopetz, M.D., Ph.D., FACP, Associate Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “These data presented at ESMO and published in The NEJM further support the potential of the BRAFTOVI Triplet to be the first chemotherapy-free, targeted regimen for this patient population, who have a poor prognosis and limited treatment options."
Further, the data provide additional details on the primary and secondary endpoints, including observations of response rates by number of lines of prior therapy, as well as a descriptive analysis of OS comparing the BRAFTOVI Triplet to the BRAFTOVI Doublet.
The BEACON CRC study was not powered to compare the two experimental arms directly and such a comparison is further limited by the interim nature of the analysis. In the data being presented at ESMO, results of the descriptive analysis of survival comparing the BRAFTOVI Triplet to the BRAFTOVI Doublet favored the Triplet combination.
Title/Abstract Number
Date/Time (CEST)
Location
(LBA32)
Encorafenib plus cetuximab with or
without binimetinib for BRAF V600E–
mutant metastatic colorectal cancer:
expanded results from a randomized,
3-arm, phase 3 study vs. the choice
of either irinotecan or FOLFIRI plus
cetuximab (BEACON CRC)
Tabernero J
Monday, September 30
8:30-8:45 AM
Barcelona
Auditorium
About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.8 million new diagnoses in 2018.1,2 In the U.S. alone, an estimated 140,250 patients were diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease each year.3 BRAF mutations are estimated to occur in up to 15% of patients with mCRC and represent a poor prognosis for these patients.4,5,6,7,8,9 The V600 mutation is the most common BRAF mutation and the risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF.7,8 BRAFV600E-mutant mCRC is an area of high unmet need as there are currently no approved therapies specifically indicated for patients with BRAF-mutant mCRC.10,[11],11
BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of BRAFTOVI, MEKTOVI and cetuximab in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAFV600E-mutant mCRC.
Thirty patients were treated in a safety lead-in conducted prior to initiation of the randomized part of the trial and received the Triplet combination (BRAFTOVI 300 mg daily, MEKTOVI 45 mg twice daily and cetuximab per label). Of the 30 patients, 29 had a BRAFV600 mutation. As previously announced, the Triplet combination showed an acceptable safety profile that supported initiation of the randomized portion of the trial.
The randomized portion of the BEACON CRC trial is designed to assess the efficacy of BRAFTOVI in combination with cetuximab with or without MEKTOVI compared to cetuximab and irinotecan-based therapy. 665 patients were randomized 1:1:1 to receive the Triplet combination, the Doublet combination (BRAFTOVI and cetuximab) or the control arm (irinotecan-based therapy and cetuximab). The study was amended to include an interim analysis of endpoints including ORR. The primary overall survival endpoint is a comparison of the Triplet combination to the control arm. Secondary endpoints address efficacy of the Doublet combination compared to the control arm, and the Triplet combination compared to the Doublet therapy. Other secondary endpoints include progression-free survival, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. The BEACON CRC trial is being conducted with support from Ono Pharmaceutical Co. Ltd., Pierre Fabre and Merck KGaA, Darmstadt, Germany (support is for sites outside of North America).
BRAFTOVI is an oral small molecule BRAF kinase inhibitor and MEKTOVI is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma. In Europe, the combination is approved for adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test. In Japan, the combination is approved for unresectable melanoma with a BRAF mutation. BRAFTOVI + MEKTOVI have received regulatory approval in Australia and the Swiss Medicines Agency (Swissmedic) is currently reviewing the Marketing Authorization Applications for BRAFTOVI and MEKTOVI submitted by Pierre Fabre.
Pfizer has exclusive rights to BRAFTOVI and MEKTOVI in the U.S. and Canada. Pfizer has granted Ono Pharmaceutical Co. Ltd. exclusive rights to commercialize both products in Japan and South Korea, Medison exclusive rights to commercialize both products in Israel and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Latin America and Asia (excluding Japan and South Korea).