Encorafenib

A slew of late-breaking presentations were shared at the American Society of Clinical Oncology this weekend, featuring potentially practice-changing results in colorectal, breast and gastric cancers. ATOMICRoche reported results from the Phase III ATOMIC study evaluating the addition of its PD-L1 inhibitor Tecentriq (atezolizumab) to standard FOLFOX chemotherapy in 712 patients with DNA mismatch repair (dMMR) colon cancer.After a median follow-up of 37.2 months, patients given the Tecentriq combo had a 50% lower risk of recurrence and death compared to patients treated with FOLFOX alone.The data could "change the standard of care" for dMMR colon cancer patients by embracing the addition of Tecentriq to FOLFOX in the adjuvant setting, said Joel Saltzman, vice chair of regional oncology at the Cleveland Clinic's Taussig Cancer Center.NIVOPOSTOPBristol Myers Squibb said its PD-1 inhibitor Opdivo (nivolumab) lowered the risk of cancer recurrence when added to chemoradiotherapy (CRT), based on the results of the Phase III NIVOPOSTOP study in 666 patients with resected locally advanced head and neck squamous cell carcinoma (HNSCC). Patients who received Opdivo plus CRT had a 24% boost to disease-free-survival versus CRT alone after 30.3 months of median follow-up. Additionally, of those taking the combination, 63.1% had no signs of cancer recurrence three years post-treatment, compared with 52.5% for the CRT alone arm.SERENA-6AstraZeneca revealed findings from the Phase III SERENA-6 study, in which patients with HR-positive/HER2-negative advanced breast cancer who switched to treatment with the oral selective oestrogen receptor degrader (SERD) camizestrant following the emergence of an ESR1 mutation during first-line therapy had a 56% reduction in the risk of disease progression or death.SERENA-6 is the first registrational trial to use a circulating tumour DNA (ctDNA)-guided approach to detect the emergence of endocrine resistance and ESR1 mutations in patients receiving first-line treatment with an aromatase inhibitor plus a CDK4/6 inhibitor. After mutation emergence, 157 patients continued with a CDK4/6 but were switched off the aromatase inhibitor and on to camizestrant, while 158 participants continued treatment with both an aromatase inhibitor and CDK4/6 inhibitor.Results showed that the camizestrant arm achieved progression-free survival (PFS) of 16 months, versus 9.2 months in the control group. At one-year, the PFS rate was 60.7% in the camizestrant group, compared to 33.4% for controls, while the rates at two years were 29.7% and 5.4%, respectively.MATTERHORNAstraZeneca's Imfinzi (durvalumab) became the first immunotherapy to demonstrate a statistically significant and clinically meaningful improvement in event-free survival (EFS) when used in the perioperative treatment setting for patients with early-stage gastric cancer and gastroesophageal junction cancer.Results from the Phase III MATTERHORN study showed that the addition of Imfinzi to standard FLOT chemotherapy before and after surgery, with follow-up treatment with AstraZeneca's PD-L1 inhibitor alone, led to a 29% improvement in EFS, as well as "a strong trend" in overall survival, compared to the FLOT regimen.Lead author Yelena Janjigian suggested that the findings "will change practice," noting that "the use of immunotherapy in earlier-stage cancers, as demonstrated in this perioperative approach…can reduce the risk of recurrence and improve cure rates."VERIFYTakeda and Protagonist presented detailed findings from the Phase III VERIFY study of rusfertide in polycythemia vera (PV), highlighting further benefits of the hepcidin mimetic beyond previously shared top-line results. New data showed significantly fewer rusfertide-treated patients required phlebotomy versus placebo recipients (27% vs 78%), and 62.6% of participants in the rusfertide group maintained haematocrit levels below 45% versus 14.4% in the placebo group. Safety outcomes were also shared for the first time in detail. No serious adverse events were linked to treatment, and the frequency of cancer events was significantly lower in the rusfertide group (0.7%) compared with placebo (4.8%).BREAKWATERPfizer said incorporating its kinase inhibitor Braftovi (encorafenib) into a combination therapy can cut the risk of death in half, based on results from the Phase III BREAKWATER study in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC).  Patients given Braftovi in combination with the EGFR inhibitor Erbitux (cetuximab) and chemotherapy had a 51% lower risk of dying and a 47% lower risk of progression than those treated with chemotherapy with or without Avastin (bevacizumab). Additionally, those taking the triplet achieved overall survival (OS) of 30.3 months and PFS of 12.8 months, versus 15.1 months and 7.1 months, respectively, for those in the control arm.ASCENT-04/KEYNOTE-D19Gilead Sciences reported that combining its Trop-2-directed antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy) with Merck & Co.'s PD-1 inhibitor Keytruda (pembrolizumab) improved survival in the 443-patient Phase III ASCENT-04/KEYNOTE-D19 study evaluating the duo in previously untreated, PD-L1-positive (CPS ≥10) metastatic triple-negative breast cancer (TNBC).Trodelvy plus Keytruda cut the risk of disease progression or death by 35% compared with the current standard of Keytruda plus chemotherapy, extending median PFS to 11.2 months versus 7.8 months for the control arm.Editors Anna Bratulic, Matthew Dennis, Elizabeth Eaton and Pavan Kamat contributed to this report.

NEW YORK, NY, USA I May 30, 2025 I Pfizer Inc. (NYSE: PFE) today announced statistically significant and clinically meaningful survival results from the Phase 3 BREAKWATER trial evaluating BRAFTOVI ® (encorafenib) in combination with cetuximab (marketed as ERBITUX ® ) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. These data will be presented today in an oral presentation (Abstract LBA3500) at the 2025 American Society of Clinical Oncology (ASCO ® ) Annual Meeting and have been simultaneously published in the New England Journal of Medicine . In a second interim analysis of overall survival (OS), a key secondary endpoint, the BRAFTOVI combination regimen reduced the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab (Hazard Ratio [HR] 0.49; 95% Confidence Interval [CI], 0.38, 0.63, p<0.0001). Median OS was 30.3 months (95% CI, 21.7, Not Estimated) with BRAFTOVIin combination with cetuximab and mFOLFOX6 compared to 15.1 months with chemotherapy with or without bevacizumab (95% CI, 13.7, 17.7). In the primary analysis of progression-free survival (PFS), the BRAFTOVI combination regimen reduced the risk of disease progression or death by 47% compared to standard-of-care chemotherapy with or without bevacizumab (HR 0.53; 95% CI, 0.41, 0.68, p<0.0001) as assessed by blinded independent central review (BICR). Median PFS was 12.8 months (95% CI, 11.2, 15.9) with the BRAFTOVI combination regimen compared to 7.1 months (95% CI, 6.8, 8.5). “Patients with metastatic colorectal cancer whose tumors harbor a BRAF V600E mutation generally face a daunting prognosis, as this aggressive tumor often does not respond well to standard-of-care chemotherapy,” said Elena Élez, M.D., Ph.D., senior investigator at Vall d’Hebron Institute of Oncology in Barcelona, Spain, and co-principal investigator of the BREAKWATER trial. “The BREAKWATER results are the first promising survival outcomes ever reported for BRAF -mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough for patients.” CRC is the third most common type of cancer in the world 1 BRAF mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis. 2 The BRAF V600E mutation is the most common BRAF mutation and the risk of mortality in patients with CRC harboring this mutation is more than double that of patients with no known BRAF mutation present. 2-4 “The BRAFTOVI combination helped significantly reduce the risk of disease progression or death, potentially altering the course of disease for people with metastatic colorectal cancer with a BRAF V600E mutation,” said Johanna Bendell, M.D., Chief Oncology Development Officer, Pfizer. “These unprecedented results from the BREAKWATER trial further establish the benefit of the BRAFTOVI combination regimen and its potential to become a new standard-of-care, building on Pfizer’s legacy in precision medicine and commitment to delivering breakthrough medicines that help people with cancer live better and longer lives.” The updated objective response rate (ORR) by BICR confirmed the improvement previously observed with the BRAFTOVI combination regimen compared to patients receiving chemotherapy with or without bevacizumab (65.7%; 95% CI, 59.4, 71.4 and 37.4%; 95% CI, 31.6, 43.7, respectively). The estimated median duration of response and median time to response were also maintained from the prior primary analysis. Results from the primary analysis of ORR were presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO GI) and were simultaneously published in Nature Medicine in January 2025. Additional data from a separate arm of the BREAKWATER study evaluating BRAFTOVI in combination with cetuximab will also be presented at ASCO. “The risk of death for patients with BRAF V600E -mutant metastatic colorectal cancer is more than double compared to those with no known mutation,” said Michael Sapienza, Chief Executive Officer, Colorectal Cancer Alliance. “These survival outcomes from the BREAKWATER study bring renewed hope to patients and their loved ones, providing the possibility of more time together. We are thrilled to see important cancer research propel us closer to our goal of ending this disease.” At the time of this analysis, the safety profile of BRAFTOVI in combination with cetuximab and mFOLFOX6 continued to be consistent with the known safety profile of each respective agent. No new safety signals were identified. The most common side effects (≥30%) were nausea, anemia, diarrhea, decreased appetite, vomiting, neutrophil count decrease, arthralgia, and rash. Among patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6, 13.8% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI. The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for patients with BRAF V600E -mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed ORR in treatment-naïve patients, the study’s other dual primary endpoint. 5 Continued approval for this indication is contingent upon verification of clinical benefit. The approval was among the first in the industry to be conducted under the FDA’s Project FrontRunner, which seeks to support the development and approval of new cancer drugs for advanced or metastatic disease. The BREAKWATER survival data are being discussed with the U.S. FDA to support potential conversion to full approval in 2025. Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries. About BREAKWATER BREAKWATER is a Phase 3, randomized, active-controlled, open-label, multicenter trial of BRAFTOVI with cetuximab, alone or in combination with mFOLFOX6 in participants with previously untreated BRAF V600E -mutant metastatic CRC. Patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab (discontinued after randomization of 158 patients), BRAFTOVI 300 mg orally once daily in combination with cetuximab and mFOLFOX6 (n=236) or mFOLFOX6, FOLFOXIRI, or CAPOX each with or without bevacizumab (control-arm) (n=243). The dual primary endpoints are ORR and progression-free survival (PFS) as assessed by blinded independent central review (BICR). Overall survival is a key secondary endpoint. About Colorectal Cancer (CRC) CRC is the third most common type of cancer in the world, with approximately 1.8 million new diagnoses in 2022. 1 It is the second leading cause of cancer-related deaths. 6 Overall, the lifetime risk of developing CRC is about 1 in 24 for men and 1 in 26 for women. 6 In the U.S. alone, an estimated 154,270 people will be diagnosed with cancer of the colon or rectum in 2025, and approximately 53,000 are estimated to die from the disease each year. 7 For 20% of those diagnosed with CRC, the disease has metastasized, or spread, making it harder to treat, and up to 50% of patients with localized disease eventually develop metastases. 8 BRAF mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis for these patients. 2 The BRAF V600E mutation is the most common BRAF mutation and the risk of mortality in patients with CRC with the BRAF V600E mutation is more than double that of patients with no known BRAF mutation present. 2-4 Despite the high unmet need in BRAF V600E -mutant mCRC, prior to December 20, 2024, there were no approved biomarker-driven therapies specifically indicated for people with previously untreated BRAF V600E -mutant mCRC. 9,10 About BRAFTOVI ® (encorafenib) BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAF V600E . Inappropriate activation of proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK) has been shown to occur in certain cancers, including CRC. Pfizer has exclusive rights to BRAFTOVI 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). INDICATION AND USAGE BRAFTOVI ® (encorafenib) is indicated, in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). BRAFTOVI is also indicated, in combination with cetuximab, for the treatment of adult patients with mCRC with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF CRC. View the full Prescribing Information . About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com . In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . References SOURCE: Pfizer