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Bayer Shares New Findings for NUBEQA® (darolutamide) Regarding Cognitive Decline in Men with Advanced Prostate Cancer Compared to Enzalutamide in Phase II ARACOG Head-to-Head Trial

On May 31, 2026 Bayer reproted primary results from the Phase II ARACOG (AFT-47) trial, a head-to-head randomized trial conducted by Alliance Foundation Trials LLC, showed that patients treated with NUBEQA (darolutamide; n=55) experienced significantly less decline in objective cognitive performance over 24 weeks compared with those treated with enzalutamide (n=56).

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NUBEQA is indicated in the U.S. for the treatment of adult patients with metastatic castration-sensitive prostate cancer (mCSPC) both with and without docetaxel, and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).1

The trial met its primary endpoint, with median cognitive change from baseline to 24 weeks in maximally changed cognitive domain (MCCD) measuring -15.8% (-38.8, -2.6) for NUBEQA compared to -36.1% (-59.3, -16.7) for enzalutamide (p=0.009) in patients with advanced prostate cancer.2 Individual cognitive domain scores increased with NUBEQA, while scores remained stable or showed mild decline with enzalutamide.2 Cognitive function was measured objectively across domains including executive function, working memory, visual memory and attention. The largest percentage change between NUBEQA and enzalutamide was observed in executive function and working memory. Executive function and working memory are primarily responsible for short term memory and management of tasks in the brain, such as following conversations, remembering directions or keeping track of information. Results were presented today as an oral abstract at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #5005; May 30, 2026. 4:24 – 4:36 PM CDT) in Chicago.

"When choosing treatment for advanced prostate cancer, physicians and patients increasingly consider not only survival and disease control, but also how treatment may affect the patient’s daily life, including cognitive function," said Alicia K. Morgans, MD, MPH, Medical Oncologist and Director of the Adult Survivorship Program at Dana-Farber Cancer Institute and Principal Investigator of the ARACOG trial. "Data such as these offer evidence that can help inform treatment discussions and support a more patient-focused approach to care."

"At Bayer, we are committed to supporting people living with prostate cancer by advancing innovative treatment options," said Dr. Frank Verholen, Global Medical & Evidence Lead for NUBEQA at Bayer. "Data have demonstrated that darolutamide does not have the same impact on the central nervous system as enzalutamide."

Secondary endpoints of ARACOG included comparison in rates of crossover, which was permitted at 12 or 24 weeks for significant pre-specified decline in cognitive testing or patient-reported outcome measures, or for central nervous system-associated adverse events, including falls.2 By 24 weeks, 32 patients in the NUBEQA arm and 33 patients in the enzalutamide arm were eligible for crossover.2 Of the 23 patients who crossed over, all had been randomized to enzalutamide and crossed over to NUBEQA, most commonly due to decline in objective (n=14) or subjective (n=11) cognitive testing.2 Patients qualified for cross-over based on worsening seen on objective or subjective cognitive tests. Longer-term follow-up of cognitive change and patient-reported outcome measure (PROM) analyses are ongoing.

Prostate cancer is the leading cancer diagnosis among men in the U.S.3 Around 313,780 men are diagnosed with prostate cancer each year in the U.S.3 By 2040, prostate cancer diagnoses are projected to increase to 2.9 million worldwide.4 For men with mCSPC, just over a third (~38%) will survive five years or more after diagnosis, and most progress to castration-resistant prostate cancer (CRPC), a condition with limited long-term survival. 5,6,7

About the ARACOG trial8

ARACOG (NCT04335682) is a U.S. prospective, randomized, open-label Phase II trial conducted by the Alliance for Clinical Trials in Oncology, evaluating objective and patient-reported cognitive and quality-of-life outcomes in patients with metastatic castration sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC) or non-metastatic castration-resistant prostate cancer (nmCRPC) treated with NUBEQA or enzalutamide.

Patients (N=111) were enrolled and randomized 1:1 to treatment with enzalutamide or NUBEQA. CANTAB, a validated computer-based platform evaluating five cognitive domains, was performed at baseline, 12, 24 and 48 weeks. The primary endpoint was the percent change in the maximally changed cognitive domain from baseline to 24 weeks and was compared between groups with the Wilcoxon rank sum statistic. Secondary endpoints included comparison of crossover rates. A study limitation was that crossover criteria included subjective outcomes in the context of an open-label trial. CANTAB is a research tool and not used for clinical diagnosis.

About NUBEQA (darolutamide)1

NUBEQA (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.

NUBEQA was developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with:

Non-metastatic castration-resistant prostate cancer (nmCRPC)
Metastatic castration-sensitive prostate cancer (mCSPC)
Metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel
IMPORTANT SAFETY INFORMATION

Warnings & Precautions
Ischemic Heart Disease – Ischemic heart disease, including fatal cases, occurred in patients receiving NUBEQA.

In a pooled analysis of ARAMIS and ARANOTE, ischemic heart disease occurred in 3.4% of patients receiving NUBEQA and 2.2% receiving placebo, including Grade 3-4 events in 1.4% and 0.3%, respectively. Ischemic events led to death in 0.4% of patients receiving NUBEQA and 0.4% receiving placebo.

In ARASENS, ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel and 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% and 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel and 0% receiving placebo with docetaxel.

Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease.

Seizure – Seizure occurred in patients receiving NUBEQA.

In a pooled analysis of ARAMIS and ARANOTE, Grade 1-3 seizure occurred in 0.2% of patients receiving NUBEQA. Seizure occurred from 261 to 665 days after initiation of NUBEQA.

In ARASENS, seizure occurred in 0.8% of patients receiving NUBEQA with docetaxel, including two Grade 3 events. Seizure occurred from 38 to 1754 days after initiation of NUBEQA.

It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.

Embryo-Fetal Toxicity – The safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo. Fatal adverse reactions that occurred in ≥2 patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common (>2% with a ≥2% increase compared to placebo) adverse reactions, including laboratory test abnormalities, were increased AST (23%), decreased neutrophil count (20%), fatigue (16%), increased bilirubin (16%), pain in extremity (6%), and rash (4%). Clinically relevant adverse reactions occurring in 2% or more of patients treated with NUBEQA included ischemic heart disease (4%) and heart failure (2.1%).

In ARANOTE, serious adverse reactions occurred in 24% of patients receiving NUBEQA. Serious adverse reactions in ≥1% of patients who received NUBEQA included pneumonia (2%), urinary tract infection (1.8%), musculoskeletal pain (1.6%), hemorrhage (1.6%), arrhythmias (1.3%), and spinal cord compression (1.1%). Fatal adverse reactions occurred in 4.7% of patients receiving NUBEQA and those that occurred in ≥2 patients included sepsis (1.1%), craniocerebral injury (0.4%), and myocardial infarction (0.4%). The most common (≥10% with a ≥2% increase compared to placebo) adverse reaction is urinary tract infection (12%). The most common laboratory test abnormalities (≥15% with a ≥5% increase over placebo) are increased AST (32%), increased ALT (28%), increased bilirubin (17%), and decreased neutrophil count (16%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA included arrhythmia (8.8%), pneumonia (3.6%), and myocardial infarction (0.7%).

In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), neutrophil count decreased (2.8%), musculoskeletal pain (2.6%) and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel. Fatal adverse reactions in ≥2 patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common (≥10% with a ≥2% increase over placebo with docetaxel) adverse reactions are constipation (23%), rash (20%), decreased appetite (19%), hemorrhage (18%), increased weight (18%), and hypertension (14%). The most common laboratory test abnormalities (≥30%) are anemia (72%), hyperglycemia (57%), decreased lymphocyte count (52%), decreased neutrophil count (49%), increased AST (40%), increased ALT (37%), and hypocalcemia (31%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures (8%), ischemic heart disease (3.2%), seizures (0.6%), and drug-induced liver injury (0.3%).

Drug Interactions

Effect of Other Drugs on NUBEQA – Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers.

Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed.

Effects of NUBEQA on Other Drugs – NUBEQA is an inhibitor of BCRP transporter. Concomitant use of NUBEQA increases the AUC and Cmax of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug.

NUBEQA is an inhibitor of OATP1B1 and OATP1B3 transporters. Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor patients more frequently for adverse reactions of these drugs and consider dose reduction while patients are taking NUBEQA.

Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

(Press release, Bayer, MAY 31, 2026, View Source [SID1234666278])

Kelonia Therapeutics Presents Updated First-in-Human Data from Phase 1 inMMyCAR Study of KLN-1010 in vivo BCMA CAR-T Therapy at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting

On May 31, 2026 Kelonia Therapeutics, Inc., a clinical-stage biotechnology company pioneering in vivo gene delivery, reported positive updated results from inMMyCAR, the ongoing first-in-human Phase 1 study of KLN-1010 in patients with relapsed and refractory multiple myeloma (RRMM), at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois.

Fourteen additional patients have been dosed since first clinical data were reported at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2025 Annual Meeting, bringing the total number of patients dosed to 18. The interim data presented at ASCO (Free ASCO Whitepaper) demonstrate a 100% overall response rate (ORR) and minimal residual disease (MRD)-negative bone marrow at one month post treatment in all evaluable patients.

Additional highlights of the updated data presented today:

First patient treated remains in deep, ongoing MRD-negative response beyond 10 months
Six patients with ≥ 4 months of follow up include 4 stringent complete response (sCR) and 2 very good partial response (VGPR), all with ongoing MRD-negative bone marrows
Robust generation and sustained persistence of CAR-T cells in the peripheral blood and bone marrow exceeding what is typically seen with ex vivo CAR-T therapies
Continued favorable safety and tolerability profiles; safety review committee has approved outpatient infusion
16 of 18 patients experienced cytokine release syndrome (CRS); all were Grade 1-2
One Grade 1 and one Grade 3 immune effector-cell associated neurotoxicity syndrome (ICANS) event; Grade 3 event was limited to 3 days
No delayed neurotoxicity observed
Cytopenias and Grade 3-4 infections were notably limited
No infusion-related reactions (IRRs) following dexamethasone premedication implementation
"The clinical data presented today at ASCO (Free ASCO Whitepaper) strengthens our conviction that the iGPS platform has the potential to transform the treatment experience and outcomes for patients with serious hematologic malignancies," said Kevin Friedman, Ph.D., Chief Executive Officer and Founder of Kelonia. "This expanded patient cohort continues to provide clear clinical validation of KLN-1010 and our platform. Durable and deep responses were achieved without the need for preparative chemotherapy or complex CAR-T cell manufacturing that impact patient access and treatment timelines. Combined with a safety profile consistent with traditional CAR-T therapies in multiple myeloma, we are seeing growing evidence for the potential of KLN-1010 to democratize CAR-T treatment of multiple myeloma."

"Early data from Kelonia’s lead in vivo CAR-T program continues to demonstrate highly encouraging responses in additional patients, with the benefit of extended follow-up revealing a consistent pattern of strong clinical responses over time, and a continued favorable safety profile," said ASCO (Free ASCO Whitepaper) Presenter and inMMyCAR investigator, Professor Joy Ho, MBBS, D.Phil, Royal Prince Alfred Hospital, Sydney, Australia. "The persistent generation of CAR-T cells observed across the expanded cohort reinforces the potential of KLN-1010 to make a meaningful difference for multiple myeloma patients."

Eli Lilly and Company’s proposed acquisition of Kelonia Therapeutics announced in April 2026 is pending transaction close.

About KLN-1010

KLN-1010, which has received Fast Track designation from the U.S. Food and Drug Administration (FDA), is an investigational in vivo gene therapy that generates anti-BCMA CAR-T cells, targeting the BCMA protein expressed on the surface of multiple myeloma cells. Unlike traditional CAR-T treatments, KLN-1010 is administered to patients via direct infusion and is designed to generate durable CAR-T cells inside the body after a single dose, potentially eliminating the need for long wait times to receive treatment. This may overcome several limitations faced by current CAR-T approaches, including limited access to treatment and the requirement of preconditioning chemotherapy.

About inMMyCAR

inMMyCAR is a Phase 1, open-label, dose-escalation clinical trial designed to assess the safety, tolerability, pharmacology and preliminary efficacy of a single dose of KLN-1010 in up to 40 patients. The primary endpoints are incidence and severity of treatment-emergent adverse events (TEAEs), including dose limiting toxicities (DLTs), and to establish the recommended Phase 2 dose of KLN-1010. Additional information and study site information may be found on clinicaltrials.gov (NCT07075185).

About Relapsed and Refractory Multiple Myeloma

Multiple myeloma is a hematologic malignancy characterized by the proliferation of plasma cells in the bone marrow, leading to bone destruction, anemia, renal dysfunction, and immunosuppression. It is driven by complex genetic and epigenetic alterations that promote malignant cell survival and resistance to apoptosis. Relapsed and refractory multiple myeloma is characterized by clonal evolution, drug resistance, and increased disease heterogeneity, heightening the need for accessible, personalized therapeutic strategies.

(Press release, Kelonia Therapeutics, MAY 31, 2026, View Source [SID1234666277])

Pfizer’s BRAFTOVI Regimen Nearly Doubles Median Progression-Free Survival in Metastatic Colorectal Cancer

On May 31, 2026 Pfizer Inc. (NYSE: PFE) reported detailed progression-free and overall survival results from Cohort 3, a randomized cohort of the Phase 3 BREAKWATER trial, evaluating BRAFTOVI (encorafenib) in combination with cetuximab (marketed as ERBITUX) and FOLFIRI (fluorouracil, leucovorin, and irinotecan) versus FOLFIRI with or without bevacizumab in patients with previously untreated metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. These results will be presented today in a late-breaking oral presentation (Abstract LBA3503) at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published in the Annals of Oncology.

As previously reported, Cohort 3 met its primary endpoint of objective response rate (ORR) by blinded independent central review (BICR). Results for the key secondary endpoint of progression-free survival (PFS) by BICR, being presented at ASCO (Free ASCO Whitepaper), show median PFS was nearly doubled with the BRAFTOVI combination regimen (15.2 months) versus the comparator (8.3 months). A clinically meaningful and statistically significant 56% reduction in the risk of disease progression or death was observed for patients treated with the BRAFTOVI combination regimen versus the comparator (Hazard Ratio [HR] of 0.44; 95% Confidence Interval [CI], 0.27–0.70; p=0.0002).

Updated overall survival (OS), a descriptive secondary endpoint, showed a 44% reduction in the risk of death for patients treated with the BRAFTOVI combination regimen versus the comparator (HR of 0.56; 95% CI, 0.34–0.94) with a median follow-up of approximately 20 months for both arms. At 18 months, 72% of patients receiving the BRAFTOVI combination regimen were expected to be alive compared to 54.5% of patients receiving the comparator. Median OS was not reached for the BRAFTOVI combination regimen versus a median of 20.3 months for the comparator.

"For people with BRAF V600E-mutant metastatic colorectal cancer – a disease that historically has had no targeted treatment options and poor outcomes – these results strengthen confidence in how we can treat this disease," said Scott Kopetz, M.D., Ph.D., FACP, Professor and Deputy Chair of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center and co-principal investigator of the BREAKWATER trial. "A nearly 60% reduction in risk of disease progression or death, combined with prolonged overall survival, reinforces the role of encorafenib in combination with cetuximab and FOLFIRI as a standard of care in the first-line setting for this patient population."

"These compelling results add to a robust body of evidence demonstrating the efficacy of the BRAFTOVI combination treatment across two different established chemotherapy regimens in BRAF V600E-mutant metastatic colorectal cancer," said Jeff Legos, Chief Oncology Officer, Pfizer. "These findings reaffirm the established role of the BRAFTOVI combination regimen as a cornerstone of first-line treatment for patients and families facing this challenging diagnosis."

In this Cohort 3 analysis, the safety profile of BRAFTOVI in combination with cetuximab and FOLFIRI continued to be consistent with the known safety profile of each respective agent in the regimen, and no new safety signals were identified. The most common adverse events (AEs) (≥25%) in the BRAFTOVI regimen were nausea, diarrhea, vomiting, anemia, alopecia, fatigue, decreased neutrophil count, constipation, decreased appetite, neutropenia, arthralgia, asthenia, and abdominal pain. Grade ≥3 AEs (all causality) occurred in 70.4% of patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI compared to 80.9% of patients receiving FOLFIRI with or without bevacizumab. Treatment discontinuation occurred in 15.5% of patients receiving the BRAFTOVI combination compared to 10.3% for those receiving FOLFIRI.

Based on the totality of the Phase 3 and Cohort 3 data in the BREAKWATER study, BRAFTOVI in combination with cetuximab and fluorouracil-based chemotherapy received full approval with an expanded indication from the U.S. Food and Drug Administration (FDA) for patients with BRAF V600E-mutant mCRC in February 2026, offering flexibility in chemotherapy regimen used.

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 chemotherapy (mFOLFOX6 or FOLFIRI) in participants with previously untreated BRAF V600E-mutant mCRC. 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, with or without bevacizumab (control arm) (n=243). The dual primary endpoints for these study groups are ORR and PFS as assessed by BICR. OS is a key secondary endpoint. In Cohort 3, patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab and FOLFIRI (n=73) or FOLFIRI, with or without bevacizumab (control-arm) (n=74). The primary endpoint of Cohort 3 is ORR as assessed by BICR. PFS as assessed by BICR is a key secondary endpoint; OS is a 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.2 Overall, the lifetime risk of developing CRC is about 1 in 24 for men and 1 in 26 for women.2 In the U.S. alone, an estimated 158,850 people will be diagnosed with cancer of the colon or rectum in 2026, and approximately 55,000 are estimated to die from the disease each year.3 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.4

BRAF mutations are estimated to occur in 8-12% of people with mCRC and are associated with a poor prognosis for these patients.5 The BRAF V600E mutation is the most common BRAF mutation, and the risk of mortality in CRC patients with the BRAF V600E mutation is more than double that of patients with no known mutation present.5-7 Despite the high unmet need in BRAF V600E-mutant mCRC, prior to the BRAFTOVI accelerated FDA approval in this indication on December 20, 2024, there were no approved biomarker-driven therapies specifically indicated for people with previously untreated BRAF V600E-mutant mCRC.8,9

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 fluorouracil-based chemotherapy, for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-authorized test.

Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF CRC.

IMPORTANT SAFETY INFORMATION
Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 and FOLFIRI for recommended dosing and additional safety information.

WARNINGS AND PRECAUTIONS

New Primary Malignancies: New primary malignancies, cutaneous and noncutaneous, can occur. In the BREAKWATER trial, the following cutaneous malignancies occurred in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6: melanocytic nevus in 5.6%, skin papilloma in 3%, basal cell carcinoma in 1.3%, squamous cell carcinoma of skin in 0.9%, keratoacanthoma in 0.4% and malignant melanoma in situ in 0.4%. In patients who received BRAFTOVI in combination with cetuximab and FOLFIRI, skin papilloma occurred in 2.8% and keratoacanthoma in 1.4% of patients. Perform dermatologic 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. Based on its mechanism of action, BRAFTOVI may promote malignancies associated with activation of RAS through mutation or other mechanisms. Monitor patients receiving BRAFTOVI for signs and symptoms of noncutaneous malignancies. Discontinue BRAFTOVI for RAS mutation-positive noncutaneous malignancies. Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment.

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-authorized test prior to initiating BRAFTOVI.

Cardiomyopathy: Cardiomyopathy manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients. Assess left ventricular ejection fraction (LVEF) by echocardiogram or multigated 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). Patients with cardiovascular risk factors should be monitored closely. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Hepatotoxicity: Hepatotoxicity can occur. In the BREAKWATER trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6 was 2.6% for alkaline phosphatase, 1.3% each for ALT and AST. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 1.5% each for ALT and AST. Monitor liver laboratory tests before initiation of BRAFTOVI, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Hemorrhage: Hemorrhage can occur. In the BREAKWATER trial, hemorrhage occurred in 34% of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6; Grade 3 or 4 hemorrhage occurred in 3% of patients. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, hemorrhage occurred in 21% of patients. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

Uveitis: Uveitis, including iritis and iridocyclitis, has been reported in patients treated with BRAFTOVI. In BREAKWATER, the incidence of uveitis among patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6 was 0.4%. 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.

QT Prolongation: BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients. In the BREAKWATER trial, an increase of QTcF >500 ms was measured in 4% (9/226) of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, an increase of QTcF >500 ms was measured in 1.5% (1/65) of 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.

Embryo-Fetal Toxicity: BRAFTOVI can cause fetal harm when administered to pregnant women. BRAFTOVI can render hormonal contraceptives ineffective. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with BRAFTOVI and for 2 weeks after the final dose.

Risks Associated with Combination Treatment: BRAFTOVI is indicated for use as part of a regimen in combination with cetuximab and mFOLFOX6 or FOLFIRI. Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 and FOLFIRI for additional risk information.

Lactation: Advise women not to breastfeed during treatment with BRAFTOVI and for 2 weeks after the final dose.

Infertility: Advise males of reproductive potential that BRAFTOVI may impair fertility.

ADVERSE REACTIONS

BRAF V600E mutation-positive mCRC, in combination with cetuximab and mFOLFOX6

Serious adverse reactions occurred in 46% of patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6. Serious adverse reactions in >3% of patients included intestinal obstruction (4.7%), pyrexia (3.9%), sepsis (3.4%), and abdominal pain (3.4%)
Fatal intestinal obstruction occurred in 0.9%, and fatal large intestinal perforation and gastrointestinal perforation occurred in 0.4% (each) in patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6
Most common adverse reactions (≥25%, all grades) in the BRAFTOVI with cetuximab and mFOLFOX6 arm compared to the control arm (mFOLFOX6 ± bevacizumab or FOLFOXIRI ± bevacizumab or CAPOX ± bevacizumab), and a subset of the control arm (mFOLFOX6 ± bevacizumab), respectively were: peripheral neuropathy (64% vs 53% and 57%), nausea (54% vs 50% and 44%), fatigue (53% vs 41% and 45%), diarrhea (42% vs 50% and 44%), decreased appetite (38% vs 27% and 30%), rash (36% vs 6% and 5%), vomiting (36% vs 22% and 17%), hemorrhage (34% vs 21% and 15%), abdominal pain (32% vs 31% and 30%), arthralgia (32% vs 6% and 7%), pyrexia (29% vs 16% and 17%), and constipation (27% vs 23% and 25%)
Most common laboratory abnormalities(≥10%, grade 3 or 4) in the BRAFTOVI with cetuximab and mFOLFOX6 arm compared to the control arm (mFOLFOX6 ± bevacizumab or FOLFOXIRI ± bevacizumab or CAPOX ± bevacizumab), and a subset of the control arm (mFOLFOX6 ± bevacizumab), respectively were: increased lipase (53% vs 28% and 23%), decreased neutrophil count (37% vs 35% and 33%), decreased hemoglobin (19% vs 6% and 7%), decreased white blood cell count (12% vs 8% and 6%), and increased glucose (11% vs 2% and 1%)
BRAF V600E mutation-positive mCRC, in combination with cetuximab and FOLFIRI

Serious adverse reactions occurred in 39% of patients who received BRAFTOVI in combination with cetuximab and FOLFIRI. Serious adverse reactions in >3% of patients included febrile neutropenia (5.6%) and infusion related reaction (4.2%)
Fatal gastrointestinal perforation occurred in 1.4% of patients who received BRAFTOVI in combination with cetuximab and FOLFIRI
Most common adverse reactions (>25%, all grades) in the BRAFTOVI with cetuximab and FOLFIRI arm compared to the control arm (FOLFIRI ± bevacizumab) were nausea (61% vs 57%), diarrhea (55% vs 49%), fatigue (47% vs 50%), vomiting (47% vs 31%), alopecia (35% vs 22%), constipation (31% vs 29%), abdominal pain (30% vs 22%), decreased appetite (30% vs 32%), and rash (27% vs 1.5%)
Most common laboratory abnormalities (≥10%, grade 3 or 4) in the BRAFTOVI with cetuximab and FOLFIRI arm compared to the control arm (FOLFIRI ± bevacizumab) were: decreased neutrophil count (30% vs 32%), increased lipase (22% vs 12%), decreased white blood cell count (20% vs 6%), and decreased hemoglobin (10% vs 3%)
DRUG INTERACTIONS
Strong or moderate CYP3A4 inhibitors: Avoid coadministration of BRAFTOVI with strong or moderate CYP3A4 inhibitors, including grapefruit juice. If coadministration is unavoidable, reduce the BRAFTOVI dose.

Strong CYP3A4 inducers: Avoid coadministration of BRAFTOVI with strong CYP3A4 inducers.

Sensitive CYP3A4 substrates: Avoid the coadministration of BRAFTOVI with CYP3A4 substrates (including hormonal contraceptives) for which a decrease in plasma concentration may lead to reduced efficacy of the substrate. If the coadministration cannot be avoided, see the CYP3A4 substrate product labeling for recommendations.

Dose reductions of drugs that are substrates of OATP1B1, OATP1B3, or BCRP may be required when used concomitantly with BRAFTOVI.

Avoid coadministration of BRAFTOVI with drugs known to prolong QT/QTc interval.

(Press release, Pfizer, MAY 31, 2026, View Source [SID1234666276])

GRAIL Presents PATHFINDER 2 Results of More Than 35,000 Participants Showing the Galleri® Test Substantially Increased Cancer Detection With Robust Performance and Favorable Safety at 2026 ASCO Annual Meeting

On May 31, 2026 GRAIL, Inc. (Nasdaq: GRAL), a healthcare company whose mission is to detect cancer early when it can be cured, reported that positive performance and safety results from the analysis of the full 35,878 cohort of its registrational PATHFINDER 2 study are being presented during an oral session at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

The PATHFINDER 2 study evaluated the safety and performance of the Galleri multi-cancer early detection (MCED) test when used alongside standard-of-care cancer screenings in the U.S. and Canada. The prospective PATHFINDER 2 study is the largest interventional study of an MCED in North America to date and includes 35,878 participants in a broad, intended-use population of adults aged 50 and older with no clinical suspicion of cancer.

"Cancer outcomes depend not only on better treatments, but on finding cancer before it advances and spreads. Earlier detection can open the door to more treatment options at any stage and increase the chance for cure," said Josh Ofman, MD, MSHS, President and CEO-Elect at GRAIL. "These PATHFINDER 2 results add to the growing body of clinical evidence in a large, representative intended-use population showing that the Galleri test can meaningfully increase cancer detection beyond recommended screening with strong performance and a highly favorable safety profile. Along with the NHS-Galleri trial results, these findings reinforce the clinical benefit of Galleri and its potential to transform early cancer detection at population scale."

Galleri Increases the Number of Cancers Detected and Can Detect Them Early

While effective screening improves early cancer detection, in the U.S., only 14% of all cancers are detected by guideline-recommended screening tests[2]. In PATHFINDER 2, 60% of diagnosed cancers were screen-detected (264/440). Adding Galleri to recommended screenings for breast, cervical, colorectal, and lung cancers (USPSTF A and B recommendations) led to a 6.5 fold increase in the number of cancers found by screening. Galleri detected nearly three times as many cancers when added to standard-of-care screening for breast, cervical, colorectal, lung, and prostate cancers (USPSTF A, B, and C recommendations).

More than half (53.0%) of the new cancers detected by Galleri were stage I or II, and 71.3% of these have no USPSTF A and B recommended screening. More than two-thirds (70.9%) of the new cancers detected by Galleri were detected at stages I-III, when treatment with curative intent is more often possible.

"PATHFINDER 2 provides important additional data on the performance and safety of MCED testing," said Karthik Giridhar, M.D., assistant professor of oncology at Mayo Clinic and a principal investigator on the PATHFINDER 2 study. "MCED tests are not a replacement for existing screening, but they have the potential to complement current approaches by helping detect cancer signals across multiple cancer types, including some for which routine screening is not currently available."

Robust Performance Metrics Consistent with Previous Studies

The Galleri test detected a cancer signal in 287 participants, and of those, cancer was diagnosed in 173 participants. The likelihood of receiving a cancer diagnosis following a positive test result (positive predictive value or PPV) was 60.3%, consistent with previously reported initial results of PATHFINDER 2 and higher than the first PATHFINDER study.

Since PATHFINDER 2 is a prospective clinical trial where the cancer status of participants is unknown at the outset, episode sensitivity – the ability to detect cancer that could be confirmed within 12 months after the blood draw – is evaluated in the study. Galleri demonstrated strong performance, with 69.8% episode sensitivity for the 12 cancers responsible for two-thirds of cancer deaths in the U.S. For all cancers, episode sensitivity was 39.3%.

Specificity was 99.6%, translating to a false positive rate of less than 0.4%.

"The up to 6.5 fold improvement in screen-detected cancers with Galleri in PATHFINDER 2 study, coupled with the greater than 20% reduction in Stage 4 cancers observed in the NHS-Galleri trial, is really exciting data that help support Galleri’s performance in a diverse and representative population," said Nima Nabavizadeh, MD, Associate Professor of Radiation Medicine at Oregon Health & Science University. "As an oncologist, I have seen too many patients diagnosed only after their cancer has spread, when treatment decisions become more difficult. By helping find more cancers earlier, when more treatment options may be available, there is great potential for multi-cancer early detection to transform cancer screening."

Galleri Pinpoints Cancer Signal Origin Allowing Efficient Diagnostic Workups

A key benefit of the Galleri test is its ability to predict where in the body the cancer signal is coming from. The PATHFINDER 2 study demonstrated that the test correctly identified the Cancer Signal Origin (CSO) 91.3% of the time, leading to efficient diagnostic workups. Diagnostic resolution took a median of 48 days, and only 0.6% of all safety-analyzable participants had an invasive procedure (213/35,335) following a positive MCED test result. A total of 90.5% of invasive procedures were nonsurgical.

Screening with the Galleri test had a favorable safety profile, with a low false-positive rate and a low rate of invasive procedures. There were five study-related adverse events reported during diagnostic evaluation, only in those with cancer diagnosis. Anxiety temporarily increased for participants with a positive MCED test and subsequent cancer diagnosis, and returned to baseline by 12 months, as has been observed for other screening tests. One serious adverse event related to the diagnostic work-up was identified after the data lock. Follow-up is ongoing; this and any other findings after data lock will be reported in full in the next interim analysis.

About PATHFINDER 2 (NCT05155605)
PATHFINDER 2 is a prospective, multi-center, interventional study evaluating the safety and performance of Galleri in approximately 35,000 individuals aged 50 years and older who are eligible for guideline-recommended cancer screening in the United States. The primary objectives of the study are 1) to evaluate the safety and performance of the Galleri MCED test based on the number and type of diagnostic evaluations performed in participants who receive a cancer signal detected test result, and 2) to evaluate the performance of the Galleri MCED test across various measures, including PPV, negative predictive value (NPV), episode sensitivity, specificity, and CSO prediction accuracy. Participants who receive a cancer signal detected result undergo additional diagnostic testing based on the predicted CSO to determine if a cancer is present. Secondary objectives include utilization of guideline-recommended cancer screening procedures after use of the MCED test, and participant reported outcomes over several time points, including an assessment of participants’ anxiety and satisfaction with the MCED test.

(Press release, Grail, MAY 31, 2026, View Source [SID1234666272])

Johnson & Johnson’s Phase 3 prostate cancer study shows ERLEADA® (apalutamide) before and after surgery significantly reduces risk of metastasis or death, breaking a decades-long treatment paradigm

On May 31, 2026 Johnson & Johnson (NYSE:JNJ) reported results from the final analysis of the Phase 3 PROTEUS study showing the investigational use of apalutamide plus hormone therapy (androgen deprivation therapy, ADT), given for six months before and after prostate cancer surgery, significantly improved key short- and long-term clinical outcomes for patients with high-risk localized or locally advanced disease. The trial met both primary endpoints. Patients treated with apalutamide plus hormone therapy were nine times more likely to have little to no cancer remaining at the time of surgery compared with hormone therapy alone (8.9 percent vs. 1.0 percent; pathologic complete response/minimal residual disease). The combination also reduced the risk of developing metastasis or death by 20 percent and extended the time before patients required subsequent therapy to more than six years. These findings will be presented in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Oral Abstract #LBA1) and published simultaneously in The New England Journal of Medicine.1,2

The unmet need with standard treatments for patients with high-risk localized prostate cancer

Surgery to remove the prostate (radical prostatectomy) is one of the standard treatments for patients with high-risk localized or locally advanced disease, alongside radiation therapy.3,4 Yet nearly half of patients who undergo curative-intent surgery will see their cancer return, requiring additional treatment and moving beyond the point where cure is possible.5,6,7 Additional therapies are often used only after the cancer has spread, missing a critical window to intervene earlier and improve long-term outcomes.8

Apalutamide blocks androgen hormones from binding to their receptor, which can help slow prostate cancer progression. It is currently approved for use in advanced prostate cancer, including cases where the disease has spread (metastatic castration-sensitive) or is no longer responding to certain hormone therapies (non-metastatic castration-resistant prostate cancer).9

Expert perspectives on the perioperative use of ERLEADA plus hormone therapy six months before and after prostate cancer surgery

"Reducing the risk of prostate cancer recurrence and death with improved initial treatment regimens has been a longstanding unmet need for patients with localized high-risk prostate cancer," said Mary-Ellen Taplin,* M.D., FASCO, medical oncologist at Dana-Farber Cancer Institute and Harvard Medical School, and principal investigator. "The PROTEUS trial demonstrates that adding preoperative apalutamide to androgen deprivation therapy and surgery reduced the risk of metastases or death by 20 percent. This result is most impactful as it may reduce the need for subsequent therapies and related side effects, while also increasing potential cure rates. This approach, which combines systemic therapy with surgery, is already standard in other aggressive cancers and now has proven benefit in patients with this disease."

"For decades, surgery has been the standard approach for many patients with high-risk localized or locally advanced prostate cancer, but these data suggest it may not be enough on its own," said Adam Kibel,† M.D., urologic surgeon and chair of the Department of Urology at Mass General Brigham. "Earlier integration of apalutamide has the potential to reshape how prostate cancer is treated by building on curative-intent surgical treatment and improving outcomes for these patients."

Detailed PROTEUS study results

PROTEUS is a Phase 3 study evaluating apalutamide, an androgen receptor pathway inhibitor, combined with hormone therapy before and after surgery in patients with newly diagnosed high-risk localized or locally advanced prostate cancer (n=2109). The dual primary endpoints were the amount of cancer remaining at surgery (pathologic complete response/minimal residual disease, pCR/MRD) and how long patients lived without the cancer spreading (metastasis-free survival, MFS), both assessed by blinded independent central review.1

At a median follow-up of 61.7 months, apalutamide plus hormone therapy met both primary endpoints. The rate of pCR/MRD was 8.9 percent with apalutamide plus hormone therapy versus 1.0 percent with hormone therapy alone (odds ratio [OR], 10.17; 95 percent confidence interval [CI], 5.27-19.64; p<0.0001). Apalutamide plus hormone therapy also demonstrated a statistically significant 20 percent reduction in the risk of metastasis or death (hazard ratio [HR], 0.80; 95 percent CI, 0.67-0.96; p=0.02), with five-year rates of 78.2 percent versus 73.5 percent, respectively. Similar metastasis-free survival results were observed in investigator assessments (HR, 0.74; 95 percent CI, 0.62-0.87; p=0.0004).1

Key secondary endpoints also showed statistically significant and clinically relevant improvement, reinforcing the benefit of the combination across multiple measures of disease control. Notably, patients receiving one year of apalutamide plus hormone therapy before and after surgery went more than six years before needing subsequent therapy, compared to approximately three and a half years with hormone therapy alone (74.2 vs. 41.5 months; HR, 0.65; 95 percent CI, 0.57-0.73; p<0.0001). Most patients also recovered adequate testosterone levels within 8.1 months. Additional benefits included a 29 percent reduction in the risk of disease recurrence or death (event-free survival; HR, 0.71; 95 percent CI, 0.63-0.80; p<0.0001) and improvements in time to distant metastasis (HR, 0.68; 95 percent CI, 0.55-0.83; p=0.0002). Improvements were also seen in MRD as assessed by residual cancer burden rates (30.6 percent vs. 11.7 percent; OR, 3.36; 95 percent CI, 2.67-4.23; nominal p<0.0001), further supporting the depth of response.1

The safety profile of apalutamide plus hormone therapy was consistent with previous studies. The most common adverse events among patients receiving apalutamide included hot flush (63.4 percent), urinary incontinence (50.2 percent) and erectile dysfunction (41.6 percent). Grade 3 or 4 adverse events occurred in 39.6 percent of patients treated with apalutamide plus hormone therapy, compared to 31.0 percent of those receiving hormone therapy alone. Discontinuations due to adverse events occurred in 7.4 percent and 2.7 percent of patients, respectively. Adverse events of special interest were generally comparable between treatment arms, with a higher incidence of skin rash observed with apalutamide. Rates of deaths were similar between treatment arms. In the apalutamide arm, deaths were more often unrelated to prostate cancer, while in the placebo arm, deaths were more frequently associated with disease progression or metastasis.1

"These findings point to a new potential way of treating patients with high-risk localized or locally advanced prostate cancer," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "Apalutamide has already shown an overall survival benefit in advanced disease. Now we’re seeing its impact when used earlier, alongside surgery. As the first therapy in its class to show benefit in this setting, these data reinforce apalutamide’s differentiated profile and the need to move beyond a surgery–only approach to treating earlier and improving long–term outcomes."

Ongoing study of ERLEADA in this setting

Apalutamide plus hormone therapy has not yet been approved by regulatory authorities in this setting. Additional analyses from the PROTEUS study, including ongoing evaluations against current standards of care such as surgery alone, are underway to further contextualize these findings and inform future treatment approaches.

About the PROTEUS study

PROTEUS (NCT03767244) is a randomized, double-blind, placebo-controlled Phase 3 study evaluating apalutamide in combination with androgen deprivation therapy (ADT) in patients with high-risk localized or locally advanced prostate cancer who are candidates for radical prostatectomy. Approximately 2,000 patients were enrolled and randomized to receive apalutamide or placebo, each in combination with ADT, administered before and after radical prostatectomy with pelvic lymph node dissection. Patients with distant metastatic disease, as determined by conventional imaging, were excluded from the study.10

Apalutamide was administered orally at 240 mg once daily. All study participants underwent protocol-defined surgery and were followed for long-term outcomes, including recurrence and progression. The dual primary endpoints of the study are pathologic complete response (pCR) and metastasis-free survival (MFS), with pCR assessed by blinded independent central pathology review and MFS assessed by blinded independent central radiology review.10

About High-Risk Localized or Locally Advanced Prostate Cancer

Approximately 330,000 people are diagnosed with prostate cancer each year in the U.S.11 Up to 40 percent of patients will be classified as high-risk.12 Despite advancements in treatment, disease recurrence remains substantial in patients with high-risk localized or locally advanced prostate cancer; up to 50 percent of patients within five years of surgery experience recurrence and carry a significant risk of disease progression and death.5,6 It’s estimated that more than 36,000 patients will succumb to prostate cancer in 2026, which reinforces the importance of choosing the best possible therapy early for patients with advanced prostate cancer.8,12

About ERLEADA

ERLEADA (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). ERLEADA received U.S. Food and Drug Administration (FDA) approval for nmCRPC in February 2018 and received U.S. FDA approval for mCSPC in September 2019. To date, more than 340,000 patients worldwide have been treated with ERLEADA.9 Additional studies are ongoing to evaluate ERLEADA in earlier stages of prostate cancer, including high-risk localized and locally advanced disease.

The legal manufacturer for ERLEADA is Janssen Biotech, Inc. For more information, visit www.ERLEADAHCP.com.

INDICATIONS

ERLEADA (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with:

Metastatic castration-sensitive prostate cancer (mCSPC)
Non-metastatic castration-resistant prostate cancer (nmCRPC)
ERLEADA IMPORTANT SAFETY INFORMATION9

WARNINGS AND PRECAUTIONS

Cerebrovascular and Ischemic Cardiovascular Events, including events leading to death, occurred in patients receiving ERLEADA. Monitor for signs and symptoms of ischemic heart disease and cerebrovascular disorders. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Consider discontinuation of ERLEADA for Grade 3 and 4 events.

In a randomized study (SPARTAN) of patients with nmCRPC, ischemic cardiovascular events occurred in 3.7% of patients treated with ERLEADA and 2% of patients treated with placebo. In a randomized study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred in 4.4% of patients treated with ERLEADA and 1.5% of patients treated with placebo. Across the SPARTAN and TITAN studies, 4 patients (0.3%) treated with ERLEADA and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular event. Patients with history of unstable angina, myocardial infarction, congestive heart failure, stroke, or transient ischemic attack within 6 months of randomization were excluded from the SPARTAN and TITAN studies.

In the SPARTAN study, cerebrovascular events occurred in 2.5% of patients treated with ERLEADA and 1% of patients treated with placebo. In the TITAN study, cerebrovascular events occurred in 1.9% of patients treated with ERLEADA and 2.1% of patients treated with placebo. Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

Fractures occurred in patients receiving ERLEADA. Evaluate patients for fracture risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.

In a randomized study (SPARTAN) of patients with nmCRPC, fractures occurred in 12% of patients treated with ERLEADA and in 7% of patients treated with placebo. In a randomized study (TITAN) of patients with mCSPC, fractures occurred in 9% of patients treated with ERLEADA and in 6% of patients treated with placebo.

Falls occurred in patients receiving ERLEADA with increased frequency in the elderly. Evaluate patients for fall risk.

In a randomized study (SPARTAN), falls occurred in 16% of patients treated with ERLEADA compared with 9% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure.

Seizure occurred in patients receiving ERLEADA. Permanently discontinue ERLEADA in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA. Advise patients of the risk of developing a seizure while receiving ERLEADA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.

In two randomized studies (SPARTAN and TITAN), five patients (0.4%) treated with ERLEADA and one patient treated with placebo (0.1%) experienced a seizure. Seizure occurred from 159 to 650 days after initiation of ERLEADA. Patients with a history of seizure or, predisposing factors for seizure, or receiving drugs known to decrease the seizure threshold or to induce seizure were excluded. There is no clinical experience in re-administering ERLEADA to patients who experienced a seizure.

Severe Cutaneous Adverse Reactions — Fatal and life-threatening cases of severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) occurred in patients receiving ERLEADA.

Monitor patients for the development of SCARs. Advise patients of the signs and symptoms of SCARs (eg, a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). If a SCAR is suspected, interrupt ERLEADA until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, or for other Grade 4 skin reactions, permanently discontinue ERLEADA [see Dosage and Administration (2.2)].

Interstitial Lung Disease (ILD)/Pneumonitis — Fatal and life-threatening interstitial lung disease (ILD) or pneumonitis can occur in patients treated with ERLEADA.

Post-marketing cases of ILD/pneumonitis, including fatal cases, occurred in patients treated with ERLEADA. Across clinical trials (TITAN and SPARTAN, n=1327), 0.8% of patients treated with ERLEADA experienced ILD/pneumonitis, including 0.2% who experienced Grade 3 events [see Adverse Reactions (6.1, 6.2)].

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold ERLEADA if ILD/pneumonitis is suspected.

Permanently discontinue ERLEADA in patients with severe ILD/pneumonitis or if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.2)].

Embryo-Fetal Toxicity — The safety and efficacy of ERLEADA have not been established in females. Based on findings from animals and its mechanism of action, ERLEADA can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA [see Use in Specific Populations (8.1, 8.3)].

ADVERSE REACTIONS

The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA-treated patients (≥2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.

Laboratory Abnormalities — All Grades (Grade 3-4)

Hematology — In the TITAN study: white blood cell decreased ERLEADA 27% (0.4%), placebo 19% (0.6%). In the SPARTAN study: anemia ERLEADA 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA 41% (1.8%), placebo 21% (1.6%)
Chemistry — In the TITAN study: hypertriglyceridemia ERLEADA 17% (2.5%), placebo 12% (2.3%). In the SPARTAN study: hypercholesterolemia ERLEADA 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA 70% (2%), placebo 59% (1.0%); hypertriglyceridemia ERLEADA 67% (1.6%), placebo 49% (0.8%); hyperkalemia ERLEADA 32% (1.9%), placebo 22% (0.5%)
Rash — In 2 randomized studies (SPARTAN and TITAN), rash was most commonly described as macular or maculopapular. Adverse reactions of rash were 26% with ERLEADA vs 8% with placebo. Grade 3 rashes (defined as covering >30% body surface area [BSA]) were reported with ERLEADA treatment (6%) vs placebo (0.5%).

The onset of rash occurred at a median of 83 days. Rash resolved in 78% of patients within a median of 78 days from onset of rash. Rash was commonly managed with oral antihistamines and topical corticosteroids, and 19% of patients received systemic corticosteroids. Dose reduction or dose interruption occurred in 14% and 28% of patients, respectively. Of the patients who had dose interruption, 59% experienced recurrence of rash upon reintroduction of ERLEADA.

Hypothyroidism — In 2 randomized studies (SPARTAN and TITAN), hypothyroidism was reported for 8% of patients treated with ERLEADA and 1.5% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA and 7% of patients treated with placebo. The median onset was at the first scheduled assessment. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose adjusted.

DRUG INTERACTIONS

Effect of Other Drugs on ERLEADA

ERLEADA Strong CYP2C8 or CYP3A4 Inhibitors

Reduce the ERLEADA dose as recommended for adverse reactions [see Dosage and Administration (2.2)]. Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady–state exposure of the active moieties (sum of unbound apalutamide plus the potency–adjusted unbound N-desmethyl-apalutamide).

Effect of ERLEADA on Other Drugs

Substrates of CYP3A4, CYP2C9, CYP2C19, P-gp, BCRP, or OATP1B1

Refer to the Prescribing Information for these substrates. Consider alternative agents when possible or evaluate for loss of activity of the substrate if concomitant use cannot be avoided.

Apalutamide is a strong inducer of CYP3A4 and CYP2C19, a weak inducer of CYP2C9, and an inducer of P-gp, BCRP, and OATP1B1. Apalutamide decreases exposure of substrates of CYP3A4, CYP2C19, CYP2C9, P-gp, BCRP, or OATP1B [see Clinical Pharmacology (12.3)], which may decrease the effectiveness of these substrates.
USE IN SPECIFIC POPULATIONS

The recommended ERLEADA dosage in patients with (Child-Pugh C) is lower than the recommended dosage in patients with normal hepatic function. No dosage modification is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

(Press release, Johnson & Johnson, MAY 31, 2026, View Source;johnsons-phase-3-prostate-cancer-study-shows-erleada-apalutamide-before-and-after-surgery-significantly-reduces-risk-of-metastasis-or-death-breaking-a-decades-long-treatment-paradigm-302786429.html [SID1234666271])