Fluorouracil

New evidence for established standard-of-care therapies, with updates for LORBRENA ® in ALK-positive metastatic non ‑ small cell lung cancer and a BRAFTOVI ® regimen in a type of BRAF-mutant colorectal cancer NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (NYSE: PFE) will present new data across its diverse, industry-leading Oncology pipeline and portfolio at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 29 – June 2, 2026, in Chicago. Data from more than 40 company-sponsored, investigator-sponsored and collaborative research abstracts, including three late-breaking sessions and eight oral and rapid oral presentations, will be shared. These data highlight Pfizer’s leadership in establishing potential new standards of care across multiple cancer types and its next-generation pipeline of novel targets and combination strategies designed to extend impact into broader patient populations and earlier lines of therapy. “For people living with cancer and their families, every moment matters. We are moving with urgency to drive advances that have the potential to change standards of care – and striving to bring new, innovative options to patients in earlier lines of therapy,” said Jeff Legos, Chief Oncology Officer, Pfizer. “Our progress is evident in the data presented at ASCO this year, which span our portfolio of established therapies, as well as next-generation, early-stage clinical research from one of the industry’s largest oncology R&D programs. Together, these results reinforce our ability to advance breakthroughs that may redefine clinical practice and change the lives of people with cancer.” Key highlights of Pfizer’s presence at ASCO include: Sharing new evidence for standard-of-care therapies in certain types of biomarker-driven colorectal and lung cancers Seven-year update from the pivotal Phase 3 CROWN study further supports LORBRENA ® (lorlatinib) as a guideline-recommended first-line treatment for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). Late-breaking presentation of progression-free survival (PFS) and overall survival (OS) data from Cohort 3 of the BREAKWATER* trial evaluating BRAFTOVI ® (encorafenib) in combination with cetuximab and FOLFIRI (fluorouracil, leucovorin and irinotecan) as a first-line regimen for patients with BRAF V600E- mutant metastatic colorectal cancer (mCRC). These pivotal data further establish the benefit of this BRAFTOVI regimen following the U.S. Food and Drug Administration (FDA) full approval and the topline results announcement for objective response rate (ORR) from this Cohort earlier this year. Showcasing data on potential benefit of treatments in earlier lines of therapy for prostate and breast cancers Late-breaking presentation from the Phase 3 TALAPRO-3 study will highlight clinically meaningful radiographic progression-free survival (rPFS) benefit for TALZENNA ® (talazoparib) plus XTANDI ® ** (enzalutamide) in metastatic castration‑sensitive prostate cancer (mCSPC) patients with homologous recombination repair gene alterations, with effects consistent across subgroups and a strong OS trend. These data follow the announcement of topline results in March 2026 and support the potential of TALZENNA plus XTANDI to deliver benefit earlier in the disease course. Additional efficacy and safety outcomes by stratified subgroups from the Phase 3 HER2CLIMB-05 study investigating TUKYSA ® (tucatinib) in combination with trastuzumab and pertuzumab as first-line maintenance therapy for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). These results support TUKYSA’s potential use as part of a chemotherapy-free, first-line maintenance strategy for HER2+ MBC. Advancing next-generation pipeline of novel mechanisms and differentiated combinations across solid tumors Updated Phase 2 data for PF‑08634404 (PF’4404), a novel bispecific antibody targeting PD-1 and VEGF, as monotherapy in first-line PD-L1-expressing NSCLC. PF’4404 is being developed as a potential backbone therapy across tumor types, including an ongoing Symbiotic-Lung-01 Phase 3 study in combination with chemotherapy in first-line NSCLC regardless of PD-L1 expression and an ongoing Symbiotic-GI-03 Phase 3 study in first-line mCRC. Updated results from a Phase 1 study of sigvotatug vedotin (SV), a novel integrin β6 (IB6)–directed ADC, in combination with pembrolizumab in NSCLC. These data support the ongoing SigVie-003 Phase 3 study of SV in combination with pembrolizumab in first-line NSCLC. An additional ongoing Phase 3 study, SigVie-002, is evaluating SV monotherapy in patients previously treated for advanced NSCLC. The first results from a Phase 2 study of neoadjuvant atirmociclib, a highly selective CDK4 inhibitor, in combination with letrozole versus letrozole alone in people with hormone receptor-positive (HR+), HER2- breast cancer. Atirmociclib is being developed as a potential first-in-class, next-generation cell cycle inhibitor backbone for HR+, HER2- breast cancer in the early adjuvant and first-line metastatic setting. Findings from a Phase 1b study of a brain-penetrant MEK inhibitor, PF-07799544 (polfurmetinib), plus a next-generation BRAF inhibitor, PF-07799933 (claturafenib), in advanced BRAF-mutant melanoma. Information on significant Pfizer and partner-sponsored abstracts, including date and time of presentation, follows in the chart below. A complete list of Pfizer and partner-sponsored abstracts and presentations is available here. LUNG CANCER Oral Presentation (Abstract 8502) May 29, 2026 1:00 PM-4:00 PM CDT Lorlatinib vs crizotinib as first-line treatment for advanced ALK+ non-small cell lung cancer: 7-year update from the phase 3 CROWN study Mok et al Rapid Oral Presentation (Abstract 8514) May 30, 2026 1:15 PM-2:45 PM CDT Updated results from a phase 2 trial of SSGJ-707 (PF-08634404), a PD-1/VEGF bispecific antibody, as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) Wu et al Poster Presentation (Abstract 8522) May 31, 2026 9:00 AM-12:00 PM CDT Sigvotatug vedotin (SV), an investigational integrin beta-6 (IB6)–directed antibody-drug conjugate (ADC), plus pembrolizumab: updated results from phase 1 study (SGNB6A-001) Jaime et al Poster Presentation (Abstract 8609) May 31, 2026 9:00 AM-12:00 PM CDT Reduction in circulating tumor DNA (ctDNA) significantly correlates with radiographic response and tumor PD-L1 expression in a phase 1 study of PDL1V (PF-08046054) in patients with non-small cell lung cancer (NSCLC) Saleh et al COLORECTAL CANCER Oral Presentation (Abstract LBA3503) May 31, 2026 8:00 AM-11:00 AM CDT BREAKWATER: Progression-free survival analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC) [LBA] Kopetz et al BREAST CANCER Oral Presentation (Abstract 1005) June 2, 2026 9:45 AM-12:45 PM CDT Efficacy and safety of tucatinib (TUC) vs placebo (PBO) combined with trastuzumab and pertuzumab (HP) as maintenance therapy for HER2+ metastatic breast cancer (MBC) by stratified randomized subgroups Hamilton et al Rapid Oral Presentation (Abstract LBA1018) May 31, 2026 11:30 AM-1:00 PM CDT Palbociclib plus Tamoxifen ± goserelin in women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (BC): PATHWAY, an Asian international double-blind randomized phase 3 trial: Final Overall Survival (OS) analysis [LBA] Lu et al Poster Presentation (Abstract 518) June 1, 2026 1:30 PM-4:30 PM CDT Neoadjuvant atirmociclib plus letrozole versus letrozole alone in women with HR+/HER2− breast cancer: results from FOURLIGHT-2, a randomized phase 2 window of opportunity study Goel et al Poster Presentation (Abstract 1042) June 1, 2026 1:30 PM-4:30 PM CDT Tucatinib (TUC) combined with trastuzumab and pertuzumab (HP) as first-line (1L) maintenance therapy for HER2+ metastatic breast cancer (MBC): an in-depth safety analysis of HER2CLIMB-05 Dieras et al Poster Presentation (Abstract 1068) June 1, 2026 1:30 PM-4:30 PM CDT Long-term safety and adverse event (AE) management in patients with ER+/HER2− metastatic breast cancer (mBC) receiving prifestrastat, a first-in-class KAT6 inhibitor, in combination with fulvestrant Layman et al BLADDER/GENITOURINARY CANCERS Oral Presentation (Abstract LBA5007) May 30, 2026 3:00 PM-6:00 PM CDT TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations [LBA] Agarwal et al Oral Presentation (Abstract 4507) May 29, 2026 2:45 PM-5:45 PM CDT Enfortumab vedotin plus pembrolizumab (EV+P) vs chemotherapy for previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): 3.5-year follow-up and response analyses from the phase 3 EV-302 study Powles et al Oral Presentation (Abstract 4510) May 30, 2026 8:00 AM-9:30 AM CDT Health-related quality of life (HRQoL) with neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin ineligible: phase 3 KEYNOTE-905 study [MSD led] O’Donnell et al Oral Presentation (Abstract 5006) May 30, 2026 3:00 PM-6:00 PM CDT Final results from ZZFIRST: a randomized phase 2 trial of enzalutamide (EZ) and talazoparib (TALA) in metastatic hormone-naïve prostate cancer (mHNPC) Mateo et al Poster Presentation (Abstract 4613) May 31, 2026 9:00 AM-12:00 PM CDT Neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants with cisplatin-ineligible muscle-invasive bladder cancer (MIBC): An analysis of clinically relevant subgroups in KEYNOTE-905 [MSD led] Adra et al Poster Presentation (Abstract 5043) May 31, 2026 9:00 AM-12:00 PM CDT Impact of baseline demographics on therapy management in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with talazoparib (TALA) + enzalutamide (ENZA) in the TALAPRO-2 study: extended follow-up De Giorgi et al MELANOMA Rapid Oral Presentation (Abstract 9512) May 30, 2026 4:30 PM-6:00 PM CDT Phase 1b study of a brain-penetrant MEK inhibitor, PF-07799544, plus next-generation BRAF dimer inhibitor, PF-07799933, in advanced BRAF-mutant melanoma Chen et al MULTIPLE MYELOMA Oral Presentation (Abstract 7500) May 29, 2026 2:45 PM-5:45 PM CDT Safety and efficacy of elranatamab as early intervention in patients with high-risk smoldering myeloma: First results from the phase 2 ERASMM (EMN34) study Touzeau et al OTHER GYNECOLOGICAL CANCERS Poster Presentation (Abstract 5627) June 1, 2026 9:00 AM-12:00 PM CDT A phase 2 study evaluating SSGJ-707 (PF-08634404), a PD-1/VEGF bispecific antibody, + chemotherapy (chemo) in patients (pts) with first-line (1L) advanced/recurrent endometrial cancer (EC) Zhou et al 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 at ASCO, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries. *The BREAKWATER trial was conducted with support from ONO Pharmaceutical, Merck KGaA, Darmstadt, Germany and Eli Lilly and Company. Pierre Fabre Laboratories also has exclusive rights to commercialize the product in all other countries, including Europe and Asia (excluding Japan and South Korea). **XTANDI® is jointly developed and commercialized by Pfizer and Astellas in the United States. Prescribing Information for Pfizer Medicines Please see full Prescribing Information for LORBRENA® (lorlatinib). Please see full Prescribing Information for BRAFTOVI® (encorafenib). Please see full Prescribing Information for TALZENNA® (talazoparib). Please see full Prescribing Information for XTANDI® (enzalutamide). Please see full Prescribing Information for TUKYSA® (tucatinib). 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 multispecific antibodies, including immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, gastrointestinal cancer, genitourinary cancer, hematologic malignancies, and lung cancers. 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. 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Scientists have discovered that a protein linked to cell death is secretly driving the aging of blood stem cells in a completely different way. Instead of killing the cells, it damages their mitochondria, sapping their energy and weakening the immune system over time. When this protein was turned off, stem cells remained stronger and more balanced, even under stress. The findings point to a new strategy for slowing aging at its source.As people get older, their blood and immune systems gradually lose strength. A major reason is the decline of hematopoietic stem cells (HSCs), which are responsible for producing all types of blood cells. Under healthy conditions, these stem cells can renew themselves and create a balanced mix of blood cells. Over time, however, they become less efficient. They generate fewer new cells, begin to favor certain types such as myeloid cells over lymphoid cells, and are less capable of supporting a strong immune response. Several factors appear to drive this decline, including accumulated cellular damage, changes in gene activity, chronic low-level inflammation, and shifts in the bone marrow environment. Even so, scientists have not fully understood how these different stresses combine to impair HSC function. Investigating a Key Aging Pathway To better understand this process, researchers from The University of Tokyo, Japan, and St. Jude Children's Research Hospital, USA, explored how age-related stress affects HSCs. They focused on the receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase like (MLKL) signaling axis, which is typically associated with necroptosis, a form of programmed cell death. The study was led by Dr. Masayuki Yamashita, an Assistant Member at St. Jude Children's Research Hospital, who, at the time of the investigation, was an Assistant Professor at The Institute of Medical Science, The University of Tokyo. Co-authors included Dr. Atsushi Iwama from The Institute of Medical Science, The University of Tokyo, and Dr. Yuta Yamada from St. Jude Children's Research Hospital, who was a graduate student at The Institute of Medical Science, The University of Tokyo. A Surprising Discovery About MLKL The research began with an unexpected observation. Dr. Yamashita explains, "We discovered an unexpected phenotype in HSCs of MLKL-knockout mice repeatedly treated with 5-fluorouracil, where aging-associated functional changes were markedly attenuated despite no detectable difference in HSC death, prompting us to investigate whether this pathway might induce functional changes beyond cell death." This finding suggested that MLKL might influence stem cell aging without actually killing the cells. That idea became central to the study, which was published in Volume 17 of Nature Communications on April 6, 2026. How Scientists Tested the Mechanism To explore this possibility, the researchers used several types of genetically engineered mice, including wild-type, MLKL-deficient, and RIPK3-deficient models. They also used specialized reporter mice designed to detect MLKL activation using a Förster resonance energy transfer-based biosensor. The mice were exposed to different stress conditions that mimic aging, such as inflammation, replication stress, and oncogenic stress. To measure how well HSCs functioned, the team relied mainly on bone marrow transplantation, which tests the ability of stem cells to rebuild the blood system. Additional techniques provided deeper insights, including flow cytometry, ex vivo expansion, RNA-seq, assay for transposase-accessible chromatin-seq, high-resolution imaging, metabolic testing, and detailed studies of mitochondria. Together, these approaches allowed the researchers to examine how MLKL affects HSCs at multiple levels. Mitochondrial Damage Without Cell Death The results revealed a previously unknown role for MLKL in stem cell aging. Although MLKL is usually linked to cell death, its activation in HSCs did not increase cell death or reduce cell numbers. Instead, it acted in a different way. When activated under stress, MLKL briefly moved to the mitochondria, the structures that generate energy within cells. There, it caused damage by lowering membrane potential, altering mitochondrial structure, and reducing energy production. These effects led to key features of aging in HSCs, including reduced ability to renew themselves, decreased production of lymphoid cells, and a shift toward myeloid cell output. Blocking MLKL Preserves Stem Cell Function When MLKL was removed or inactivated, many of these problems were significantly reduced. HSCs lacking MLKL retained their ability to regenerate, produced healthier immune cells, showed less DNA damage, and maintained better mitochondrial function. These benefits were seen even in older animals or under stressful conditions. Notably, these improvements occurred without major changes in gene expression or chromatin accessibility. This suggests that MLKL influences aging through processes that occur after gene activity, particularly at the level of cellular structures like mitochondria, rather than through changes in DNA regulation or inflammation. Implications for Aging and Future Therapies The findings point to a common pathway that connects various types of cellular stress to mitochondrial damage and stem cell aging. By identifying MLKL as a key link in this process, the study offers new insight into how aging affects the blood system. Dr. Yamashita emphasizes, "In the longer term, this research could lead to therapies that preserve the function of hematopoietic stem cells, ultimately improving recovery and long-term health for patients undergoing chemotherapy, radiation, or transplantation. By revealing how non-lethal activation of cell-death pathways drives stem cell aging, these findings may inspire new classes of mitochondrial-protective or necroptosis-modulating drugs." A New Understanding of Stem Cell Aging Overall, the study reveals that MLKL plays an important role in stem cell aging without causing cell death. Instead, it responds to stress by damaging mitochondria and weakening HSC function over time. This discovery challenges traditional views of necroptosis-related proteins and opens new possibilities for slowing or preventing age-related decline in the blood and immune systems.