Vemurafenib

NEW YORK--( BUSINESS WIRE )-- Pfizer Inc. (NYSE: PFE) today announced longer-term follow-up results from the Phase 2 single-arm PHAROS clinical trial evaluating the efficacy and safety of BRAFTOVI ® (encorafenib) in combination with MEKTOVI ® (binimetinib) for patients with BRAF V600E - mutant metastatic non-small cell lung cancer (NSCLC). After an additional 18 months of follow-up, the objective response rate (ORR) and the median duration of response (DoR) as assessed by independent radiology review were 75% and 40 months in treatment-naïve patients and 46% and 16.7 months in previously treated patients, respectively. In addition, after approximately three years of follow-up in treatment-naïve patients, the median progression-free survival (PFS) with BRAFTOVI + MEKTOVI was 30.2 months (95% confidence interval [CI], 15.7-not estimable [NE]), while median overall survival (OS) was not yet reached (95% CI, 31.3-NE). These data will be presented today during a late-breaking oral session (Abstract LBA56) at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain. “ BRAF V600E-mutant metastatic non-small cell lung cancer tends to be aggressive, and effective targeted first-line treatment options with manageable safety profiles are critical for the thousands of people who are diagnosed globally each year,” said Gregory Riely, M.D., Ph.D., Vice Chair, Clinical Research in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK) and PHAROS investigator. “ The longer-term follow-up results from the PHAROS trial represent an important step forward in the treatment of BRAF V600E-mutant metastatic NSCLC, especially for treatment-naïve patients. These compelling results support the BRAFTOVI + MEKTOVI combination as a standard of care option for these patients.” Lung cancer is the number one cause of cancer-related death around the world. 1 NSCLC accounts for approximately 80-85% of lung cancers, 2 with BRAF V600E mutations occurring in about 2% of patients with NSCLC. 3 Understanding the role of the mitogen-activated protein within the pathway including BRAF V600E-mutant metastatic NSCLC. The Phase 2 PHAROS trial ( NCT03915951 ) is an open-label, multicenter, single arm study examining BRAFTOVI + MEKTOVI combination therapy in treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC. Notably, upon longer-term follow-up in previously treated patients, BRAFTOVI + MEKTOVI showed a median PFS of 9.3 months (95% CI, 6.2-24.8) and a median OS of 22.7 months (95% CI, 14.1-32.2), with a safety profile that was consistent with previous findings; no new safety concerns were identified. In this analysis, treatment-related adverse events (AEs) led to dose reduction in 26% of patients, and to permanent discontinuation in 16% of patients. Nausea, diarrhea, and fatigue remained the most common treatment-related AEs. “ These potentially practice-changing results from the PHAROS trial show that the combination of BRAFTOVI + MEKTOVI is providing long-term compelling efficacy for patients, and although no definitive conclusions can be made across trials, the duration of response and progression-free survival in treatment naïve patients appear to be the longest observed for BRAF V600E–mutant metastatic NSCLC compared with historical outcomes,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “ These latest data reflect our deep understanding of the science behind biomarker-driven cancers and add to our legacy in developing innovative targeted treatments in NSCLC. We are continuing to build upon this strong foundation with a pipeline of targeted medicines and combinations across our tumor areas of focus, including the ongoing investigation of BRAFTOVI in earlier settings of metastatic colorectal cancer, and the exploration of a next-generation brain-penetrant BRAF inhibitor.” BRAFTOVI + MEKTOVI was approved by the U.S. Food and Drug Administration (FDA) in October 2023, and by the European Commission in August 2024, for the treatment of BRAF V600E-mutant metastatic NSCLC based on the initial ORR (the primary endpoint) and DoR (key secondary endpoint) results from the PHAROS clinical trial. In addition to PHAROS, safety lead-in data from the ongoing Phase 3 BREAKWATER study investigating BRAFTOVI in combination with cetuximab and FOLFIRI chemotherapy in previously untreated BRAF V600E-mutant metastatic colorectal cancer (CRC) will also be presented as a mini-oral session at ESMO (Abstract 515MO). BRAFTOVI in combination with cetuximab and FOLFIRI was found to be generally tolerable in this patient population, with no new safety concerns identified. These findings support the ongoing investigation of this combination regimen as a potential treatment option for BRAF V600E-mutant metastatic CRC. The Phase 3 BREAKWATER trial is ongoing, with updated data expected in 2025. BRAF mutations can occur in a number of tumor types, including metastatic melanoma, metastatic CRC and metastatic NSCLC. Among different types of BRAF mutations, the BRAF V600E mutation is particularly important as it occurs in approximately half of patients with BRAF -mutant metastatic NSCLC. 4 Further, this mutation represents up to 90% of BRAF mutations in melanoma 5 and more than doubles the risk of mortality for patients with CRC. 6 In addition to our continued investigation of BRAFTOVI + MEKTOVI for BRAF- mutant cancers, Pfizer is also exploring a next-generation BRAF inhibitor designed to selectively inhibit mutant BRAF monomers and mutant BRAF- containing dimers and be brain penetrant. The investigational drug is currently being evaluated in a Phase 1 clinical study. Pfizer has exclusive rights to BRAFTOVI + MEKTOVI in the U.S., Canada, and all countries in Latin America, Africa and the Middle East. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialize both products in Japan and South Korea, Medison has exclusive rights in Israel, and Pierre Fabre Laboratories has exclusive rights in all other countries, including Europe and Asia-Pacific (excluding Japan and South Korea). The PHAROS trial is conducted with support from Pierre Fabre Laboratories. INDICATION AND USAGE BRAFTOVI ® (encorafenib) and MEKTOVI ® (binimetinib) are kinase inhibitors indicated for use in combination for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. BRAFTOVI is indicated, in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. BRAFTOVI and MEKTOVI are kinase inhibitors indicated for use in combination for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test. Limitations of Use : BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC. IMPORTANT SAFETY INFORMATION This information applies to the safety of BRAFTOVI when used in combination with either MEKTOVI or cetuximab. WARNINGS AND PRECAUTIONS New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous, can occur. BRAFTOVI may promote malignancies associated with activation of RAS through mutation or other mechanisms. Perform dermatopathologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Dose modification is not recommended for new primary cutaneous malignancies. Monitor patients receiving BRAFTOVI for signs and symptoms of non-cutaneous malignancies. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies. Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment. BRAF -mutant type ( BRAF -mt) metastatic melanoma (COLUMBUS study): Cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 2.6% and basal cell carcinoma occurred in 1.6% of patients receiving BRAFTOVI with MEKTOVI. Median time to first occurrence of cuSCC/KA was 5.8 months. BRAF -mt metastatic CRC (BEACON CRC study): cuSCC, including KA, occurred in 1.4% of patients with CRC, and a new primary melanoma occurred in 1.4% of patients who received BRAFTOVI with cetuximab. BRAF -mt metastatic NSCLC (PHAROS study): cuSCC and skin papilloma (SP), each occurred in 2% of patients. Tumor Promotion in BRAF Wild-Type Tumors: In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells exposed to BRAF inhibitors. Confirm evidence of BRAF V600E or V600K mutation using an FDA-approved test prior to initiating BRAFTOVI. Cardiomyopathy: Cardiomyopathy manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported. Patients with cardiovascular risk factors should be monitored closely. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. Assess left ventricular ejection fraction (LVEF) by echocardiogram or multi-gated acquisition (MUGA) scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal (LLN). BRAF -mt metastatic melanoma (COLUMBUS study): Evidence of cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients receiving BRAFTOVI with MEKTOVI. The median time to first occurrence of left ventricular dysfunction (any grade) was 3.6 months. Cardiomyopathy resolved in 87% of patients. BRAF -mt metastatic NSCLC (PHAROS study): Evidence of cardiomyopathy occurred in 11% and Grade 3 left ventricular dysfunction occurred in 1% of patients. Cardiomyopathy resolved in 82% of patients. Hepatotoxicity: Hepatotoxicity can occur. Monitor liver laboratory tests before initiation, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. BRAF -mt metastatic melanoma (COLUMBUS study): The incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving MEKTOVI with BRAFTOVI was 6% for alanine aminotransferase (ALT), 2.6% for aspartate aminotransferase (AST), and 0.5% for alkaline phosphatase. BRAF -mt metastatic NSCLC (PHAROS study): The incidence of Grade 3 or 4 increases in liver function laboratory tests was 10% for AST, 9% for ALT, and 3.2% for alkaline phosphatase. Hemorrhage: Hemorrhage can occur when BRAFTOVI is administered in combination with MEKTOVI or cetuximab. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. BRAF -mt metastatic melanoma (COLUMBUS study): Hemorrhage occurred in 19% of patients receiving BRAFTOVI with MEKTOVI and Grade 3 or higher hemorrhage occurred in 3.2% of patients. The most frequent hemorrhagic events were gastrointestinal, including rectal hemorrhage (4.2%), hematochezia (3.1%), and hemorrhoidal hemorrhage (1%). Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients. BRAF -mt metastatic CRC (BEACON CRC study): Hemorrhage occurred in 19% of patients receiving BRAFTOVI with cetuximab; Grade 3 or higher hemorrhage occurred in 1.9% of patients, including fatal gastrointestinal hemorrhage in 0.5% of patients. The most frequent hemorrhagic events were epistaxis (6.9%), hematochezia (2.3%), and rectal hemorrhage (2.3%). BRAF -mt metastatic NSCLC (PHAROS study): Hemorrhage occurred in 12% of patients including fatal intracranial hemorrhage (1%); Grade 3 or 4 hemorrhage occurred in 4.1% of patients. The most frequent hemorrhagic events were anal hemorrhage and hemothorax (2% each). Uveitis: Uveitis, including iritis and iridocyclitis, has been reported in patients treated with BRAFTOVI with MEKTOVI. Assess for visual symptoms at each visit. Perform an ophthalmological evaluation at regular intervals and for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. BRAF -mt metastatic melanoma (COLUMBUS study): The incidence of uveitis among patients treated with BRAFTOVI with MEKTOVI was 4%. BRAF -mt metastatic NSCLC (PHAROS study): The incidence of uveitis among patients treated with BRAFTOVI with MEKTOVI was 1%. QT Prolongation: BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms. BRAF -mt metastatic melanoma (COLUMBUS study): An increase in QTcF to >500 ms was measured in 0.5% (1/192) of patients who received BRAFTOVI with MEKTOVI. BRAF -mt metastatic NSCLC (PHAROS study): An increase in QTcF to >500 ms was measured in 2.1% (2/95) of patients who received BRAFTOVI with MEKTOVI. Embryo-Fetal Toxicity: Both BRAFTOVI and MEKTOVI can cause fetal harm when administered to a pregnant woman. BRAFTOVI can render hormonal contraceptives ineffective. BRAF -mt metastatic melanoma (COLUMBUS study) and BRAF -mt metastatic NSCLC (PHAROS study): Effective, non-hormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI with MEKTOVI. BRAF -mt metastatic CRC (BEACON CRC study): Advise females of reproductive potential to use effective nonhormonal contraception during treatment with BRAFTOVI and for 2 weeks after the final dose. BRAFTOVI as a Single Agent is associated with increased risk of certain adverse reactions compared to when BRAFTOVI is used with MEKTOVI. BRAF -mt metastatic melanoma (COLUMBUS study): Grades 3 or 4 dermatologic reactions occurred in 21% of patients receiving BRAFTOVI as a single agent compared to 2% in patients receiving the combination of BRAFTOVI with MEKTOVI. If MEKTOVI is temporarily interrupted or permanently discontinued, reduce the dose of BRAFTOVI as recommended. Risks Associated with Combination Treatment In BRAF -mt metastatic melanoma (COLUMBUS study) , BRAFTOVI is used in combination with MEKTOVI so refer to the prescribing information for MEKTOVI for additional risk information. In BRAF -mt metastatic CRC (BEACON CRC study) , BRAFTOVI is used in combination with cetuximab so refer to the prescribing information for cetuximab for additional risk information. In BRAF -mt metastatic NSCLC (PHAROS study) , BRAFTOVI is indicated for use as part of a regimen in combination with MEKTOVI, so refer to the prescribing information for MEKTOVI for additional risk information. Additional WARNINGS AND PRECAUTIONS for MEKTOVI When Used With BRAFTOVI Venous Thromboembolism (VTE): VTE occurred in 6% of patients with BRAF -mt metastatic melanoma (COLUMBUS study) , including 3.1% of patients who developed pulmonary embolism. VTE occurred in 7% of patients with BRAF -mt metastatic NSCLC (PHAROS study) , including 1% of patients who developed pulmonary embolism. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. Other Ocular Toxicities Serous retinopathy Assess for visual symptoms at each visit. Perform an ophthalmologic examination at regular intervals, for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. BRAF -mt metastatic melanoma (COLUMBUS study): serous retinopathy occurred in 20% of patients receiving MEKTOVI with BRAFTOVI; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. The median time to onset of the first event of serous retinopathy (all grades) was 1.2 months. BRAF -mt metastatic NSCLC (PHAROS study): serous retinopathy (retinal detachment) occurred in 2% of patients with no cases of blindness. Retinal vein occlusion (RVO) is a known class-related adverse reaction of MEK inhibitors and may occur in patients receiving MEKTOVI with BRAFTOVI. In BRAF -mt metastatic melanoma (COLUMBUS study) , 1 patient experienced RVO (0.1%) in the MEKTOVI with BRAFTOVI group (n=690). The safety of MEKTOVI has not been established in patients with a history of RVO or current risk factors for RVO, including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. Perform ophthalmological evaluation for patient-reported acute vision loss or other visual disturbance within 24 hours. Permanently discontinue MEKTOVI in patients with documented RVO. Interstitial Lung Disease (ILD): ILD, including pneumonitis, occurred in 0.3% (2 of 690 patients) with BRAF -mt metastatic melanoma (COLUMBUS study) receiving MEKTOVI with BRAFTOVI. One patient (1%) with BRAF -mt metastatic NSCLC (PHAROS study) receiving MEKTOVI with BRAFTOVI developed pneumonitis. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. Rhabdomyolysis: Rhabdomyolysis can occur when MEKTOVI is taken with BRAFTOVI. Monitor creatine phosphokinase (CPK) and creatinine levels prior to initiating MEKTOVI, periodically during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. BRAF -mt metastatic melanoma (COLUMBUS study): Elevation of laboratory values of serum CPK occurred in 58% of patients receiving MEKTOVI with BRAFTOVI. Rhabdomyolysis was reported in 0.1% (1 of 690 patients) with BRAF mutation-positive melanoma receiving MEKTOVI with BRAFTOVI. BRAF -mt metastatic NSCLC (PHAROS study): Elevation of laboratory values of serum creatine kinase (CK) occurred in 41% of patients. No patient experienced rhabdomyolysis. ADVERSE REACTIONS BRAF -mt Metastatic Melanoma (COLUMBUS study) Most common adverse reactions (≥20%, all grades) for patients receiving BRAFTOVI with MEKTOVI compared to vemurafenib were fatigue (43% vs 46%), nausea (41% vs 34%), diarrhea (36% vs 34%), vomiting (30% vs 16%), abdominal pain (28% vs 16%), arthralgia (26% vs 46%), myopathy (23% vs 22%), hyperkeratosis (23% vs 49%), rash (22% vs 53%), headache (22% vs 20%), constipation (22% vs 6%), visual impairment (20% vs 4%), serous retinopathy/RPED (20% vs 2%). Other clinically important adverse reactions occurring in <10% of patients who received BRAFTOVI with MEKTOVI were facial paresis, pancreatitis, panniculitis, drug hypersensitivity, and colitis. Most common laboratory abnormalities (≥20%, all grades) for BRAFTOVI with MEKTOVI compared to vemurafenib included increased creatinine (93% vs 92%), increased CPK (58% vs 3.8%), increased gamma glutamyl transferase (GGT) (45% vs 34%), anemia (36% vs 34%), increased ALT (29% vs 27%), hyperglycemia (28% vs 20%), increased AST (27% vs 24%), and increased alkaline phosphatase (21% vs 35%). BRAF -mt Metastatic CRC (BEACON CRC study) Most common adverse reactions (≥25%, all grades) in patients receiving BRAFTOVI with cetuximab compared to irinotecan with cetuximab or FOLFIRI with cetuximab (control) were fatigue (51% vs 50%), nausea (34% vs 41%), diarrhea (33% vs 48%), dermatitis acneiform (32% vs 43%), abdominal pain (30% vs 32%), decreased appetite (27% vs 27%), arthralgia (27% vs 3%), and rash (26% vs 26%). Other clinically important adverse reactions occurring in <10% of patients who received BRAFTOVI with cetuximab was pancreatitis. Most common laboratory abnormalities (≥20%, all grades) in the BRAFTOVI with cetuximab arm compared to irinotecan with cetuximab or FOLFIRI with cetuximab (control) were: anemia (34% vs 48%) and lymphopenia (24% vs 35%). BRAF -mt Metastatic NSCLC (PHAROS study) Most common adverse reactions (≥25%, all grades) in patients receiving BRAFTOVI with MEKTOVI were fatigue (61%), nausea (58%), diarrhea (52%), musculoskeletal pain (48%), vomiting (37%), abdominal pain (32%), visual impairment (29%), constipation (27%), dyspnea (27%), rash (27%), and cough (26%). Serious adverse reactions occurred in 38% of patients receiving BRAFTOVI with MEKTOVI. Serious adverse reactions occurring in ≥2% of patients were hemorrhage (6%), diarrhea (4.1%), anemia (3.1%), dyspnea (3.1%), pneumonia (3.1%), arrhythmia (2%), device related infection (2%), edema (2%), myocardial infarction (2%), and pleural effusion (2%). Fatal adverse reactions occurred in 2% of patients, including intracranial hemorrhage (1%) and myocardial infarction (1%). Other clinically important adverse reactions occurring in <10% of patients who received BRAFTOVI with MEKTOVI were peripheral neuropathy, dysgeusia, facial paresis, pancreatitis, hyperkeratosis, erythema, and drug hypersensitivity. Most common laboratory abnormalities (≥20%, all grades) for BRAFTOVI and MEKTOVI included increased creatinine (91%), hyperglycemia (48%), anemia (47%), increased creatine kinase (41%), lipase increased (40%), increased ALT (34%), hypoalbuminemia (32%), increased alkaline phosphatase (31%), increased AST (31%), hyperkalemia (31%), hyponatremia (26%), lymphopenia (24%), serum amylase increased (22%), and thrombocytopenia (20%). DRUG INTERACTIONS With BRAFTOVI When Used in Combination With Either MEKTOVI or Cetuximab Avoid coadministration of BRAFTOVI with strong or moderate CYP3A4 inhibitors (including grapefruit juice) or CYP3A4 inducers and use caution with sensitive CYP3A4 substrates. Avoid coadministration of BRAFTOVI with hormonal contraceptives. Modify BRAFTOVI dose if coadministration with a strong or moderate CYP3A4 inhibitor cannot be avoided. Avoid coadministration of BRAFTOVI with drugs known to prolong QT/QTc interval. Dose reductions of drugs that are substrates of OATP1B1, OATP1B3, or BCRP may be required when used concomitantly with BRAFTOVI. Lactation: Advise women not to breastfeed during treatment with BRAFTOVI and MEKTOVI and for 2 weeks after the final dose. Infertility: Advise males of reproductive potential that BRAFTOVI may impair fertility. For BRAF -mt metastatic melanoma and for BRAF -mt metastatic NSCLC, see full Prescribing Information and Medication Guide for BRAFTOVI and full Prescribing Information and Medication Guide for MEKTOVI. See full Prescribing Information for BRAFTOVI and for MEKTOVI for dose modifications for adverse reactions. There may be a delay as the documents are updated with the latest information. They will be available as soon as possible. Please check back for the updated full information shortly. For BRAF -mt metastatic CRC, see full Prescribing Information and Medication Guide for BRAFTOVI. See full Prescribing Information for BRAFTOVI for dose modifications for adverse reactions. Refer to cetuximab prescribing information for recommended dosing and safety 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 . Disclosure Notice The information contained in this release is as of September 14, 2024. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about the BRAFTOVI ® (encorafenib) and MEKTOVI® (binimetinib) combination for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, other potential indications and a next-generation BRAF inhibitor, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of BRAFTOVI plus MEKTOVI; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications may be filed in any additional jurisdictions for BRAFTOVI plus MEKTOVI for the treatment of patients with metastatic NSCLC with a BRAF V600E mutation or in any jurisdictions for any other potential indications for BRAFTOVI and MEKTOVI or any other product candidates; whether and when any such applications may be approved by regulatory authorities, which will depend on a myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether BRAFTOVI plus MEKTOVI or any such other product candidates will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of BRAFTOVI plus MEKTOVI or any other product candidates; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “ Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com . References 1 World Health Organization. International Agency for Research on Cancer. GLOBOCAN 2022: Global Population Fact sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/populations/900-world-fact-sheet.pdf . Last accessed: September 2024. 2 American Cancer Society. What is lung cancer? Available at: https://www.cancer.org/cancer/lung-cancer/about/what-is.html . Last accessed: September 2024. 3 American Lung Association. BRAF and lung cancer. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/braf . Last accessed: September 2024. 4 Paik PK, Arcila ME, Fara M, et al . Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol . 2011;29(15):2046-51. 5 Cheng L, Lopez-Beltran A, Massari F, et al . Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol . 2018;31(1):24-38. 6 Safaee Ardekani G, Jafarnejad, SM, Tan, L, et al . The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PloS ONE . 2012;7(10):e47054.

– Tecentriq Hybreza provides patients and physicians with greater flexibility of treatment options while showing safety and efficacy consistent with intravenous (IV) Tecentriq – – New subcutaneous (SC) option reduces treatment time to approximately 7 minutes, compared with 30-60 minutes for IV infusion – SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has approved Tecentriq Hybreza™ (atezolizumab and hyaluronidase-tqjs), the first and only PD-(L)1 inhibitor for subcutaneous (SC), under the skin injection for patients in the United States. Tecentriq Hybreza can be injected subcutaneously over approximately seven minutes, compared with 30-60 minutes for standard IV infusion of Tecentriq (atezolizumab). It will be available for all IV indications of Tecentriq approved for adults in the U.S., including certain types of lung, liver, skin and soft tissue cancer. “By enabling subcutaneous administration for a cancer immunotherapy, Tecentriq Hybreza now offers patients with multiple cancer types and their physicians greater flexibility and choice of treatment administration,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are pleased to introduce this new subcutaneous formulation that builds on the established safety and efficacy pro intravenous Tecentriq and can treat patients faster and in more accessible settings.” “This approval represents a significant option to improve the patient experience,” said Ann Fish-Steagall, RN, senior vice president of Patient Services at the LUNGevity Foundation. “When patients have options, they feel empowered to be vital participants in their own care and choose their preferred treatment option.” The FDA approval is based on pivotal data from the Phase IB/III IMscin001 study, which showed comparable levels of Tecentriq in the blood, when administered subcutaneously, and a safety and efficacy pro with the IV formulation. The Phase II IMscin002 study showed that 71% of patients preferred Tecentriq Hybreza over intravenous atezolizumab, and the most common reasons were less time in the clinic, increased comfort during treatment and reduced emotional distress. 4 out of 5 patients (79%) chose Tecentriq Hybreza to continue their treatment, after experiencing both formulations. Developing new formulations of our medicines is part of our commitment to improve the patient experience and support people living with different illnesses at every step of their treatment journey. With Tecentriq Hybreza and Roche/Genentech’s 13 other subcutaneous therapies – available across various diseases – we offer additional administration options to meet the diverse preferences of patients. The subcutaneous formulation of Tecentriq received its first worldwide approval in Great Britain in August 2023 and is now approved in over 50 countries (outside the U.S. marketed as Tecentriq SC). Regulatory reviews in other countries and regions are ongoing. Genentech is committed to helping people access the medicines they are prescribed and offers comprehensive services for people prescribed Tecentriq Hybreza to help minimize barriers to access and reimbursement. For people who qualify, Genentech offers patient assistance programs through Genentech Access Solutions. More information is also available at 866-4ACCESS/866-422-2377 or . Visit for additional information. About the IMscin001 study IMscin001 is a Phase IB/III, global, multicenter, randomized study evaluating the pharmacokinetics, safety and efficacy of Tecentriq Hybreza, compared with IV Tecentriq, in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) for whom prior platinum therapy has failed. The study enrolled 371 patients. The study met its primary endpoints, demonstrating comparable levels of Tecentriq in the blood during a given dosing interval on the basis of established pharmacokinetic measurements; observed serum C trough and model-predicted area under the curve. Observed efficacy, as measured by the overall response rate, progression-free survival, overall survival and duration of response, was similar between the SC and IV treatment arms and consistent with the known pro IV Tecentriq. The safety pro Tecentriq Hybreza was also consistent with that of IV Tecentriq. About the IMscin002 study IMscin002 is a Phase II, global crossover study evaluating patient preference between the SC and IV formulations of Tecentriq. The study enrolled 179 patients, including people with PD-L1-positive resected Stage II-IIIB NSCLC who have completed adjuvant platinum-based chemotherapy without evidence of disease recurrence, and untreated patients with PD-L1-high Stage IV NSCLC. The study met its primary endpoint, showing that 71% of participants preferred the SC formulation (21% preferred IV and 8% stated no preference); 79% opted for Tecentriq Hybreza to complete their treatment, after experiencing both formulations of Tecentriq. The study confirmed that switching between Tecentriq Hybreza and IV Tecentriq was well tolerated, with no new safety signals. About Tecentriq Hybreza Tecentriq Hybreza combines Tecentriq with Halozyme Therapeutics’ Enhanze ® drug delivery technology. Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells. The Enhanze drug delivery technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that locally and temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body – in the subcutaneous space. This increases the permeability of the tissue under the skin, allowing space for Tecentriq to enter, enabling it to be rapidly dispersed and absorbed into the bloodstream. Tecentriq is approved for some of the most aggressive and difficult-to-treat forms of cancer. Tecentriq was the first cancer immunotherapy approved for the treatment of a certain type of early-stage (adjuvant) NSCLC, small cell lung cancer (SCLC) and hepatocellular carcinoma (HCC). Tecentriq is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer (mUC), PD-L1-positive metastatic triple-negative breast cancer (TNBC), BRAF V600 mutation-positive advanced melanoma and alveolar soft part sarcoma (ASPS). In addition to intravenous infusion, Tecentriq has been approved as a subcutaneous formulation in over 50 countries (outside the U.S. marketed as Tecentriq SC). The approved indications for Tecentriq Hybreza and Tecentriq SC mirror those of IV Tecentriq. What is Tecentriq Hybreza? Tecentriq Hybreza is a prescription medicine used to treat: Adults with a type of lung cancer called non-small cell lung cancer (NSCLC). Tecentriq Hybreza may be used alone as a treatment for their lung cancer: to help prevent their lung cancer from coming back after their tumor(s) has been removed by surgery and they have received platinum-based chemotherapy, and they have stage 2 to 3A NSCLC (patients should talk to their healthcare provider about what these stages mean), and their cancer tests positive for “PD-L1”. Tecentriq Hybreza may be used alone as their first treatment when their lung cancer: has spread or grown, and their cancer tests positive for “high PD-L1”, and their tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq Hybreza may be used with the medicines bevacizumab, paclitaxel, and carboplatin as their first treatment when their lung cancer: has spread or grown, and is a type called “non-squamous NSCLC,” and their tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq Hybreza may be used with the medicines paclitaxel protein-bound and carboplatin as their first treatment when their lung cancer: has spread or grown, and is a type called “non-squamous NSCLC,” and their tumor does not have an abnormal “EGFR” or “ALK” gene. Tecentriq Hybreza may be used alone when their lung cancer: has spread or grown, and if they have tried chemotherapy that contains platinum, and it did not work or is no longer working. if their tumor has an abnormal “EGFR” or “ALK” gene, they should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working. Adults with a type of lung cancer called small cell lung cancer (SCLC). Tecentriq Hybreza may be used with the chemotherapy medicines carboplatin and etoposide as their first treatment when their lung cancer: is a type called “extensive-stage small cell lung cancer,” which means that it has spread or grown. Adults with a type of liver cancer called hepatocellular carcinoma (HCC). Tecentriq Hybreza may be used with the medicine bevacizumab when their liver cancer: has spread or cannot be removed by surgery, and they have not received other medicines by mouth or injection through their vein (IV) to treat their cancer. Adults with a type of skin cancer called melanoma. Tecentriq Hybreza may be used with the medicines cobimetinib and vemurafenib in patients with melanoma when their skin cancer: has spread to other parts of the body or cannot be removed by surgery, and has a certain type of abnormal “BRAF” gene. Healthcare providers will perform a test to make sure this Tecentriq Hybreza combination is right for the patient. Adults with a type of soft tissue tumor (cancer) called alveolar soft part sarcoma (ASPS). Tecentriq Hybreza may be used when their sarcoma: has spread to other parts of the body or cannot be removed by surgery. It is not known if Tecentriq Hybreza is safe and effective in children. Important Safety Information Who should not receive TECENTRIQ HYBREZA? Patients should not receive TECENTRIQ HYBREZA if they are allergic to hyaluronidase or any of the ingredients in TECENTRIQ HYBREZA. What is the most important information about Tecentriq Hybreza? Tecentriq Hybreza can cause the immune system to attack normal organs and tissues in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended. Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including: Lung problems cough shortness of breath chest pain Intestinal problems diarrhea (loose stools) or more frequent bowel movements than usual stools that are black, tarry, sticky, or have blood or mucus severe stomach-area (abdomen) pain or tenderness Liver problems yellowing of the skin or the whites of the eyes severe nausea or vomiting pain on the right side of their stomach area (abdomen) dark urine (tea colored) bleeding or bruising more easily than normal Hormone gland problems headaches that will not go away or unusual headaches eye sensitivity to light eye problems rapid heartbeat increased sweating extreme tiredness weight gain or weight loss feeling more hungry or thirsty than usual urinating more often than usual hair loss feeling cold constipation their voice gets deeper dizziness or fainting changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness Kidney problems decrease in their amount of urine blood in their urine swelling of their ankles loss of appetite Skin problems rash itching skin blistering or peeling painful sores or ulcers in mouth or nose, throat, or genital area fever or flu-like symptoms swollen lymph nodes Problems can also happen in other organs. These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq Hybreza. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including: Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight Persistent or severe muscle pain or weakness, muscle cramps Low red blood cells, bruising Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: chills or shaking itching or rash flushing shortness of breath or wheezing dizziness feeling like passing out fever back or neck pain Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq Hybreza. A healthcare provider will monitor for these complications. Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq Hybreza. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to delay or completely stop treatment with Tecentriq Hybreza if patients have severe side effects. Before receiving Tecentriq Hybreza, patients should tell their healthcare provider about all of their medical conditions, including if they: have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus have received an organ transplant have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic) have received radiation treatment to their chest area have a condition that affects their nervous system, such as myasthenia gravis or Guillain-Barré syndrome are pregnant or plan to become pregnant. Tecentriq Hybreza can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq Hybreza. Females who are able to become pregnant: A healthcare provider should do a pregnancy test before they start treatment with Tecentriq Hybreza They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq Hybreza are breastfeeding or plan to breastfeed. It is not known if Tecentriq Hybreza passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq Hybreza Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of Tecentriq Hybreza when used alone include: feeling tired or weak decreased appetite nausea cough shortness of breath The most common side effects observed with TECENTRIQ and may be experienced with TECENTRIQ HYBREZA are shown below The most common side effects of TECENTRIQ when used alone as the first treatment for NSCLC include: feeling tired or weak The most common side effects of TECENTRIQ when used alone in NSCLC that has spread or grown include: feeling tired or weak cough decreased appetite shortness of breath muscle or bone pain The most common side effects of TECENTRIQ when used in NSCLC with bevacizumab, paclitaxel, and carboplatin include: numbness, pain, tingling, or burning in your hands or feet feeling tired or weak hair loss muscle or bone pain nausea diarrhea constipation decreased appetite joint pain high blood pressure rash cough The most common side effects of TECENTRIQ when used in non-squamous NSCLC with paclitaxel protein-bound and carboplatin include: feeling tired or weak nausea diarrhea muscle or bone pain constipation numbness, pain, tingling, or burning in your hands or feet hair loss shortness of breath decreased appetite cough vomiting rash The most common side effects of TECENTRIQ when used in SCLC with carboplatin and etoposide include: feeling tired or weak nausea hair loss decreased appetite constipation vomiting The most common side effects of TECENTRIQ when used in HCC with bevacizumab include: high blood pressure feeling tired or weak too much protein in the urine The most common side effects of TECENTRIQ when used in melanoma with cobimetinib and vemurafenib include: skin rash joint, muscle, or bone pain feeling tired or weak liver injury fever nausea itching swelling of legs or arms mouth swelling (sometimes with sores) low thyroid hormone levels sunburn or sun sensitivity The most common side effects of TECENTRIQ when used alone in ASPS include: muscle or bone pain feeling tired or weak rash cough headache nausea high blood pressure vomiting constipation shortness of breath dizziness bleeding diarrhea trouble sleeping stomach-area (abdominal) pain low thyroid hormone levels fever anxiety irregular heartbeat (arrhythmia) decreased appetite Tecentriq Hybreza may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility. These are not all the possible side effects of Tecentriq Hybreza. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq Hybreza. Report side effects to the FDA at 1-800-FDA-1088 or . Report side effects to Genentech at 1-888-835-2555. Please see for full Prescribing Information and additional Important Safety Information. About Genentech in lung cancer Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have six approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease. Genentech is committed to improving treatment of early-stage lung cancers to help increase the chance of cure for more people. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit . Contacts Media Contact: Kendall Tich (650) 467-6800 Advocacy Contact: Meg Harrison (617) 694-7060 Investor Contacts: Loren Kalm (650) 225-3217 Bruno Eschli +41616875284