The Chinese National Medical Products Administration (NMPA) has granted marketing authorization for encorafenib (Braftovi®; Pfizer, Pierre Fabre Laboratories)* in combination with cetuximab (Erbitux®; Eli Lilly and Co)* for the treatment of adult patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC), after prior systemic therapy.
Encorafenib is an oral small molecule kinase inhibitor that targets BRAFV600E. Inappropriate activation of proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK) has been shown to occur in certain cancers, including mCRC.
The approval in China is based on the Phase 3 BEACON CRC trial (NCT02928224), the pivotal study that led to the approval in the European Union and the United States, that demonstrated a significant improvement in overall survival of patients treated with encorafenib in combination with cetuximab, as well as on the NAUTICAL CRC bridging study (NCT05004350) conducted in China which demonstrated similar results in Chinese patients.
The BEACON CRC trial showed that encorafenib in combination with cetuximab significantly improved overall survival in patients with BRAFV600E-mutant mCRC and the risk of death was reduced by 40% in BEACON CRC and 45% in NAUTICAL CRC.[1][2][3]
The phase 2, multi-center, randomized, open-label, 2-arm NAUTICAL CRC study evaluated encorafenib + cetuximab vs irinotecan (Camptosar®; Pfizer) + cetuximab or FOLFIRI***+ cetuximab (control arm) in Chinese patients with BRAF V600E mutant mCRC whose disease progressed after 1 or 2 prior treatment lines in the metastatic setting. The study achieved its primary objective, demonstrating an estimated 63.0% reduction in the risk of disease progression or death among Chinese subjects receiving encorafenib in combination with cetuximab compared to the control group.
“The marketing authorization for encorafenib by the Chinese health authorities is a key milestone. Greater China is a priority strategic country for Pierre Fabre Laboratories. We are proud to bring this therapeutic option to Chinese patients fighting BRAFV600E-mutant mCRC, and our teams are poised to make the launch a success in partnership with Chinese authorities and health care professionals,” noted Marie-Andrée Gamache, Chief Executive Office of Pierre Fabre Medical Care.
BRAF mutations
Patients diagnosed with mCRC with the BRAFV600E-mutation generally have a poor prognosis. The median overall survival (OS) is 4 to 6 months after failure of initial therapy. As a result of pathway reactivation through epidermal growth factor receptor signaling, inhibition of BRAF alone has only limited effect. [2]
BRAF mutations are estimated to occur in approximately 3-5% of Chinese patients diagnosed with mCRC, with V600E being the most common mutation.[4] Patients with mCRC who have BRAFV600E-mutant tumors generally have a poor prognosis representing a high unmet medical need.[5]
“This approval represents a significant advancement and is crucial for the patients in China with BRAFV600E-mutant mCRC facing this particularly unfavorable prognosis cancer. Until now, no treatment specifically intended for this population has been approved by the Chinese authorities, leaving an unmet medical need. From now, encorafenib in combination with cetuximab will change the approach to treating the patients in China, offering the possibility to slow disease progression and improve their life expectancy”, explained Núria Perez-Cullell, Head of Medical & Patient Consumer Department.
“The approval of encorafenib in China underscores our unwavering commitment to advancing care for patients facing challenging-to-treat cancers and delivering precision medicine,” said Mr. Tian Wee NG, Managing Director, Pierre Fabre Medical Care, Hong Kong/China.
Renewed hope
“The combination of encorafenib with cetuximab provides renewed hope for Chinese metastatic colorectal cancer patients with a BRAFV600E mutation, offering a targeted cancer treatment regimen. This approval highlights our dedication to addressing significant unmet medical needs within the oncology landscape and reinforces our mission to deliver innovative and accessible treatment options,” NG added.
By integrating cutting-edge science with patient-centered care, we aim to significantly enhance the quality of life for Chinese patients and contribute to the fight against cancer,” he concluded.
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Note: * Pfizer has exclusive rights to encorafenib in the U.S., Canada, Latin America, Middle East, and Africa. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialize the product in Japan and South Korea, Medison has exclusive rights to commercialize the product in Israel and Pierre Fabre Laboratories has exclusive rights to commercialize the product in all other countries, including Europe and Asia (excluding Japan and South Korea).
** In the United States and Canada, it is marketed by Eli Lilly and Company. Outside of the US and Canada, Merck KGaA commercializes Erbitux. Eli Lilly also has a collaboration with Bristol-Myers Squibb for Erbitux. A separate agreement grants co-exclusive rights among Merck, Bristol-Myers Squibb and Eli Lilly in Japan and expires in 2032.
*** FOLFIRI is a chemotherapy regimen used to treat certain types of cancer, primarily metastatic colorectal cancer. It combines fluorouracil, leucovorin (folinic acid), and irinotecan.
Clinical trials
Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer (BEACON CRC) – ClinicalTrials.gov ID NCT02928224
A Study Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer. (NAUTICALCRC) ClinicalTrials.gov ID NCT05004350
Highlights of prescribing information
Encorafenib (Braftovi®; Pfizer, Pierre Fabre Laboratories)[Prescribing information]
Cetuximab (Erbitux®; Eli Lilly and Co)[Prescribing Information]
Irinotecan (Camptosar®; Pfizer)[Prescribing Information]
Reference
[1] Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021 Feb 1;39(4):273-284. doi: 10.1200/JCO.20.02088. PMID: 33503393; PMCID: PMC8078423.
[2] Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. doi: 10.1056/NEJMoa1908075. Epub 2019 Sep 30. PMID: 31566309.
[3] NAUTICAL study was presented in part at the Annual ASCO meeting 2024. Wang X et al, Journal of Clinical Oncology, LBA3559, Volume 42, Number 17_suppl, June 2024. [Wang X et al. Encorafenib and cetuximab versus irinotecan/cetuximab or FOLFIRI/cetuximab in Chinese patients with BRAF V600E mutant metastatic colorectal cancer: The NAUTICAL CRC study.. JCO 42, LBA3559-LBA3559(2024). DOI:10.1200/JCO.2024.42.17_suppl.LBA3559]
[4] Li W, Qiu T, Ling Y, Guo L, Li L, Ying J. Molecular pathological epidemiology of colorectal cancer in Chinese patients with KRAS and BRAF mutations. Oncotarget. 2015 Nov 24;6(37):39607-13. doi: 10.18632/oncotarget.5551. PMID: 26530529; PMCID: PMC4741849.
[5] Martinelli E, Arnold D, Cervantes A, Stintzing S, Van Cutsem E, Tabernero J, Taieb J, Wasan H, Ciardiello F. European expert panel consensus on the clinical management of BRAFV600E-mutant metastatic colorectal cancer. Cancer Treat Rev. 2023 Apr;115:102541. doi: 10.1016/j.ctrv.2023.102541. Epub 2023 Mar 11. PMID: 36931147.
Featured image: Colorectal Cancer. Photo courtesy © 2018 – 2025, Fotolia/Adobe. Used with permission.
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