1stOncology™: Cancer Intelligence Service – Page 86 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Ivonescimab Plus Chemotherapy Demonstrates Statistically Significant and Clinically Meaningful Improvement in Progression-Free Survival in Patients with EGFR-Mutant Non-Small Cell Lung Cancer after EGFR TKI Therapy in Global Study

On May 30, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") reported topline results from the Phase III clinical trial, HARMONi, the first global Phase III study evaluating ivonescimab, successfully met the progression-free survival (PFS) primary endpoint and showed a positive trend in the other primary endpoint, overall survival (OS) (Press release, Summit Therapeutics, MAY 30, 2025, View Source [SID1234653538]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

HARMONi is a multiregional, double-blinded, placebo-controlled, Phase III study sponsored by Summit evaluating ivonescimab plus platinum-doublet chemotherapy compared to placebo plus platinum-doublet chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with a 3rd generation EGFR tyrosine kinase inhibitor (TKI). This is a clinical setting with a patient population where PD-1 monoclonal antibodies have previously been unsuccessful in Phase III global clinical trials in showing either a PFS or OS benefit.

Approximately 38% of patients were randomized from western countries (ex-Asia), consistent with other recent multiregional Phase III studies in patients with EGFR-mutated NSCLC.

At the prespecified primary data analysis, ivonescimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, with a hazard ratio of 0.52 (95% CI: 0.41 – 0.66; p<0.00001). PFS was measured by blinded independent central radiology review committee (BICR) compared to placebo in combination with chemotherapy. A clinically meaningful hazard ratio was observed in both Asia and ex-Asia sub-populations. The primary analysis demonstrated the consistency of the magnitude of the PFS benefit between patients randomized in Asia and ex-Asia, as well as the consistency in a single-region study (HARMONi-A) with this multiregional study.

Ivonescimab in combination with chemotherapy showed a positive trend in OS in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057). This trend provides further support for its use in 2L+ EGFRm NSCLC, a setting where high unmet need continues to exist with limited approved options in the United States and other western territories. There are no current FDA-approved regimens that have demonstrated a statistically significant overall survival benefit in this patient setting. The median follow-up time for western patients was less than the median overall survival at the time of the analysis, and these patients may continue to be followed for long-term outcomes. Both Asian and North American patients demonstrated a positive trend in overall survival. The results of the primary analysis in this multiregional study were consistent with that of the single-region HARMONi-A study, which demonstrated an overall survival hazard ratio of 0.80 at 52% data maturity in a similar patient population.

There were no new safety signals noted in this Phase III study. Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported for 56.9% of patients in the ivonescimab + chemotherapy arm vs 50.0% with chemotherapy alone. Fatal TEAEs (excluding disease progression) were reported for 1.8% of patients in the ivonescimab + chemotherapy arm vs. 2.8% in those patients receiving chemotherapy alone. The safety profile of ivonescimab + chemotherapy was acceptable and manageable in the context of the observed clinical benefit.

"The evidence of a consistent benefit in PFS for both Asian and western patients, as well as the consistent overall survival results between the single-region HARMONi-A study and our global HARMONi study demonstrates the potential benefit ivonescimab has to bring to patients around the world, including the United States," stated Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit Therapeutics.

Based on the results of the HARMONi clinical trial, Summit, at present time, intends to file a Biologics License Application (BLA) in order to seek approval for ivonescimab plus chemotherapy in this setting. Based on discussions with the United States Food & Drug Administration (FDA), under our determination and subject to our review, Summit will consider the timing of the filing of this BLA. The FDA noted that a statistically significant overall survival benefit is necessary to support marketing authorization, which will weigh into Summit’s considerations regarding the timing of a potential BLA filing.

A more complete data presentation from the clinical study is intended to be shared at a future major medical conference.

"Our conviction in the promise that this therapy holds for patients continues to be validated: we believe that ivonescimab has the potential to make a meaningful difference for the betterment of patients’ lives," added Dr. Maky Zanganeh, President and Co-CEO of Summit.

The positive Phase III HARMONi study results, along with the approval of ivonescimab in China in combination with chemotherapy based on the results of the HARMONi-A trial and the subsequent supplemental approval of ivonescimab monotherapy in China for first-line treatment of patients with advanced NSCLC whose tumors have positive PD-L1 expression based on the results of the HARMONi-2 trial, further substantiates the purposefully-engineered, differentiated mechanism of action of ivonescimab, a PD-1 / VEGF bispecific antibody evidencing cooperative binding characteristics, and its opportunity to improve upon the existing standards of care for solid tumors, including in settings where existing immune checkpoint inhibitors are indicated.

We would like to offer our heartfelt gratitude to each of the patients, physicians, nurses, and caregivers who participated in and supported this clinical study. We are grateful to the dedication of our investigators and patients who are essential in advancing innovative therapies and bringing to patients the most advanced therapies for those facing unfortunate diagnoses.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 2,300 patients have been treated with ivonescimab in clinical studies globally.

Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3, and the Company has begun to enroll patients in the United States for HARMONi-7.

HARMONi is a Phase III clinical trial which is evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib). Top-line results were announced in May 2025, which included a statistically significant and clinically meaningful benefit in progression-free survival and a positive trend in overall survival, the trial’s two primary endpoints. Consistent results were noted between the single region HARMONi-A study and the multiregional HARMONi study.

HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC.

HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI. Approximately 85% of patients received a 3rd generation EGFR-TKI prior to randomization in the study.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024, and its label was expanded in China in April 2025. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration ("FDA") for the HARMONi clinical trial setting.

Onc.AI to Present Breakthrough Deep Learning Radiomic Biomarker Results at 2025 ASCO Annual Meeting

On May 30, 2025 Onc.AI, a digital health company developing AI-powered oncology clinical management solutions, reported that new validation study results from research collaborations with Pfizer, Baylor Scott & White and the University of Rochester Medical Center will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held May 30–June 3, 2025, in Chicago, IL (Press release, Onc AI, MAY 30, 2025, View Source [SID1234653537]).

Onc.AI’s poster presentation showcases its FDA-breakthrough designated deep learning radiomics model, Serial CTRS, which evaluates changes across routine CT scans over time to predict overall survival in late-stage non–small cell lung cancer (NSCLC) and other solid tumor types. In collaboration with Baylor Scott & White and Pfizer, Serial CTRS has demonstrated:

Superior prediction of overall survival (OS): Hazard ratios (HRs) for OS improvement and stratification exceed those of the conventional imaging approach (RECIST 1.1).
Generalizability across real-world and clinical trial cohorts: Robust performance in both routine real-world datasets and a Pfizer-sponsored PD-1 checkpoint inhibitor trial.
Actionable insights for early treatment adaptation: Dynamic monitoring identifies non-responders months before conventional criteria would signal poor prognosis.
At the ASCO (Free ASCO Whitepaper) Innovation Hub (IH13), Onc.AI will share latest results from its pipeline of deep learning radiomic models to customers and partners spanning medical oncologist investigators and biopharma companies looking to accelerate oncology clinical development.

Program Highlights

Poster Presentation:

Abstract #253138: Validation of Serial CTRS for Early Immunotherapy Response Prediction in Metastatic NSCLC – View Source

Presenter: Ronan Kelly, MD, Baylor Scott & White
Date & Time: June 1, 2025; 9:00 am–12:00 pm CDT
Location: Hall A, Poster Board 325
Abstract #251996: Retrospective Single-Institution Application of a Deep Learning–Based Radiomic Score in Metastatic NSCLC: Potential Impact on First-Line Treatment Decisions – View Source

Lead Author: Nicholas Love, MD, University of Rochester
Abstract #245837: Image Harmonization for PD-(L)1 Immune Checkpoint Inhibitor Response Prediction Using Deep Learning Radiomic Features in Advanced NSCLC – View Source

Lead Author: Taly Gilat-Schmidt, PhD, Onc.AI
"These strong validation study results spanned both RWD and a pharma-sponsored clinical trial. Serial CTRS could represent a high-potential tool for medical oncologists and for optimizing pharma clinical development," said Dr. Ronan Kelly, MD, Director of Oncology at the Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas Texas

"Our retrospective study highlights how Onc.AI’s Deep Learning Radiomic baseline score can be extremely helpful to medical oncologists as a prognostic marker for first line mutation negative NSCLC patients," added Arpan Patel, MD and Associate Professor of Medical Oncology at the University of Rochester Medical Center.

Pfizer’s BRAFTOVI® Combination Regimen Cuts the Risk of Death in Half for Patients with BRAF V600E-Mutant Metastatic Colorectal Cancer

On May 30, 2025 Pfizer Inc. (NYSE: PFE) reported statistically significant and clinically meaningful survival results from the Phase 3 BREAKWATER trial evaluating BRAFTOVI (encorafenib) in combination with cetuximab (marketed as ERBITUX) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation (Press release, Pfizer, MAY 30, 2025, View Source [SID1234653536]). These data will be presented today in an oral presentation (Abstract LBA3500) at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and have been simultaneously published in the New England Journal of Medicine.

In a second interim analysis of overall survival (OS), a key secondary endpoint, the BRAFTOVI combination regimen reduced the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab (Hazard Ratio [HR] 0.49; 95% Confidence Interval [CI], 0.38, 0.63, p<0.0001). Median OS was 30.3 months (95% CI, 21.7, Not Estimated) with BRAFTOVI in combination with cetuximab and mFOLFOX6 compared to 15.1 months with chemotherapy with or without bevacizumab (95% CI, 13.7, 17.7). In the primary analysis of progression-free survival (PFS), the BRAFTOVI combination regimen reduced the risk of disease progression or death by 47% compared to standard-of-care chemotherapy with or without bevacizumab (HR 0.53; 95% CI, 0.41, 0.68, p<0.0001) as assessed by blinded independent central review (BICR). Median PFS was 12.8 months (95% CI, 11.2, 15.9) with the BRAFTOVI combination regimen compared to 7.1 months (95% CI, 6.8, 8.5).

"Patients with metastatic colorectal cancer whose tumors harbor a BRAF V600E mutation generally face a daunting prognosis, as this aggressive tumor often does not respond well to standard-of-care chemotherapy," said Elena Élez, M.D., Ph.D., senior investigator at Vall d’Hebron Institute of Oncology in Barcelona, Spain, and co-principal investigator of the BREAKWATER trial. "The BREAKWATER results are the first promising survival outcomes ever reported for BRAF-mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough for patients."

CRC is the third most common type of cancer in the world1 BRAF mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis.2 The BRAF V600E mutation is the most common BRAF mutation and the risk of mortality in patients with CRC harboring this mutation is more than double that of patients with no known BRAF mutation present.2-4

"The BRAFTOVI combination helped significantly reduce the risk of disease progression or death, potentially altering the course of disease for people with metastatic colorectal cancer with a BRAF V600E mutation," said Johanna Bendell, M.D., Chief Oncology Development Officer, Pfizer. "These unprecedented results from the BREAKWATER trial further establish the benefit of the BRAFTOVI combination regimen and its potential to become a new standard-of-care, building on Pfizer’s legacy in precision medicine and commitment to delivering breakthrough medicines that help people with cancer live better and longer lives."

The updated objective response rate (ORR) by BICR confirmed the improvement previously observed with the BRAFTOVI combination regimen compared to patients receiving chemotherapy with or without bevacizumab (65.7%; 95% CI, 59.4, 71.4 and 37.4%; 95% CI, 31.6, 43.7, respectively). The estimated median duration of response and median time to response were also maintained from the prior primary analysis. Results from the primary analysis of ORR were presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancer Symposium (ASCO GI) and were simultaneously published in Nature Medicine in January 2025. Additional data from a separate arm of the BREAKWATER study evaluating BRAFTOVI in combination with cetuximab will also be presented at ASCO (Free ASCO Whitepaper).

"The risk of death for patients with BRAF V600E-mutant metastatic colorectal cancer is more than double compared to those with no known mutation," said Michael Sapienza, Chief Executive Officer, Colorectal Cancer Alliance. "These survival outcomes from the BREAKWATER study bring renewed hope to patients and their loved ones, providing the possibility of more time together. We are thrilled to see important cancer research propel us closer to our goal of ending this disease."

At the time of this analysis, the safety profile of BRAFTOVI in combination with cetuximab and mFOLFOX6 continued to be consistent with the known safety profile of each respective agent. No new safety signals were identified. The most common side effects (≥30%) were nausea, anemia, diarrhea, decreased appetite, vomiting, neutrophil count decrease, arthralgia, and rash. Among patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6, 13.8% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI.

The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for patients with BRAF V600E -mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed ORR in treatment-naïve patients, the study’s other dual primary endpoint.5 Continued approval for this indication is contingent upon verification of clinical benefit. The approval was among the first in the industry to be conducted under the FDA’s Project FrontRunner, which seeks to support the development and approval of new cancer drugs for advanced or metastatic disease. The BREAKWATER survival data are being discussed with the U.S. FDA to support potential conversion to full approval in 2025.

Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries.

About BREAKWATER
BREAKWATER is a Phase 3, randomized, active-controlled, open-label, multicenter trial of BRAFTOVI with cetuximab, alone or in combination with mFOLFOX6 in participants with previously untreated BRAF V600E-mutant metastatic CRC. Patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab (discontinued after randomization of 158 patients), BRAFTOVI 300 mg orally once daily in combination with cetuximab and mFOLFOX6 (n=236) or mFOLFOX6, FOLFOXIRI, or CAPOX each with or without bevacizumab (control-arm) (n=243). The dual primary endpoints are ORR and progression-free survival (PFS) as assessed by blinded independent central review (BICR). Overall survival is a key secondary endpoint.

About Colorectal Cancer (CRC)
CRC is the third most common type of cancer in the world, with approximately 1.8 million new diagnoses in 2022.1 It is the second leading cause of cancer-related deaths.6 Overall, the lifetime risk of developing CRC is about 1 in 24 for men and 1 in 26 for women.6 In the U.S. alone, an estimated 154,270 people will be diagnosed with cancer of the colon or rectum in 2025, and approximately 53,000 are estimated to die from the disease each year.7 For 20% of those diagnosed with CRC, the disease has metastasized, or spread, making it harder to treat, and up to 50% of patients with localized disease eventually develop metastases.8

BRAF mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis for these patients.2 The BRAF V600E mutation is the most common BRAF mutation and the risk of mortality in patients with CRC with the BRAF V600E mutation is more than double that of patients with no known BRAF mutation present.2-4 Despite the high unmet need in BRAF V600E-mutant mCRC, prior to December 20, 2024, there were no approved biomarker-driven therapies specifically indicated for people with previously untreated BRAF V600E-mutant mCRC.9,10

About BRAFTOVI (encorafenib)
BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAF V600E. Inappropriate activation of proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK) has been shown to occur in certain cancers, including CRC.

Pfizer has exclusive rights to BRAFTOVI in the U.S., Canada, Latin America, Middle East, and Africa. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialize the product in Japan and South Korea, Medison has exclusive rights to commercialize the product in Israel and Pierre Fabre Laboratories has exclusive rights to commercialize the product in all other countries, including Europe and Asia (excluding Japan and South Korea).

INDICATION AND USAGE
BRAFTOVI (encorafenib) is indicated, in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

BRAFTOVI is also indicated, in combination with cetuximab, for the treatment of adult patients with mCRC with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.

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

IMPORTANT SAFETY INFORMATION

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

WARNINGS AND PRECAUTIONS

New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous, can occur. In BEACON CRC (previously treated BRAF V600E mutation-positive mCRC), cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 1.4% of patients with CRC, and a new primary melanoma occurred in 1.4% of patients who received BRAFTOVI in combination with cetuximab. In BREAKWATER (previously untreated BRAF V600E mutation-positive mCRC) skin papilloma was reported in 2.6%, 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% of patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6. 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 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.

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 in patients. 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. 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 BREAKWATER (previously untreated BRAF V600E mutation-positive mCRC), the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6 was 2.2% for alkaline phosphatase, 1.3% for ALT, and 0.9% for 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: In BEACON CRC (previously treated BRAF V600E mutation-positive mCRC), hemorrhage occurred in 19% of patients receiving BRAFTOVI in combination 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%). In BREAKWATER (previously untreated BRAF V600E mutation-positive mCRC), hemorrhage occurred in 30% of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6; Grade 3 or 4 hemorrhage occurred in 3% 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. 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 BREAKWATER (previously untreated BRAF V600E mutation-positive mCRC), an increase of QTcF >500 ms was measured in 3.6% (8/222) of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6. 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, or in combination with cetuximab and mFOLFOX6. Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 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

BREAKWATER Trial (previously untreated BRAF V600E mutation-positive mCRC)

Serious adverse reactions occurred in 38% of patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6. Serious adverse reactions in >3% of patients included intestinal obstruction (3.5%) and pyrexia (3.5%).
Fatal gastrointestinal perforation occurred in 0.9% of 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) were peripheral neuropathy (62% vs 53%), nausea (51% vs 48%), fatigue (49% vs 38%), rash (31% vs 4%), diarrhea (34% vs 47%), decreased appetite (33% vs 25%), vomiting (33% vs 21%), hemorrhage (30% vs 18%), abdominal pain (26% vs 27%), and pyrexia (26% vs 14%).
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) were: increased lipase (51% vs 25%), decreased neutrophil count (36% vs 34%), decreased hemoglobin (13% vs 5%), decreased white blood cell count (12% vs 7%), and increased glucose (11% vs 2%).
BEACON CRC Trial (previously treated BRAF V600E mutation-positive mCRC)

Most common adverse reactions (≥25%, all grades) in the BRAFTOVI with cetuximab arm 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 in combination with cetuximab was pancreatitis.
Most common laboratory abnormalities (all grades) (≥20%) 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%).
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.

View the full Prescribing Information.

Tempus Announces 10 Abstracts Accepted for Presentation at the 2025 American Society of Clinical Oncology Annual Meeting

On May 30, 2025 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported that ten abstracts have been accepted for presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Tempus, MAY 30, 2025, View Source [SID1234653535]). The event will take place May 30 – June 3 in Chicago, Illinois. Tempus will present its cutting-edge clinical findings and innovative technologies, highlighting the company’s use of AI-driven solutions to advance precision oncology.

"At ASCO (Free ASCO Whitepaper) 2025, we are proud to showcase a diverse portfolio of studies that highlight how our cutting-edge technologies, including tumor-naive and tumor-informed MRD monitoring, whole genomic sequencing for hematologic malignancies, and multi-omic biomarker profiling, are providing clinicians and researchers with actionable insights to personalize treatment and improve outcomes for patients," said Ezra Cohen, MD, Chief Medical Officer of Oncology at Tempus. "We are excited to share these advancements and collaborate with the oncology community to shape the future of precision medicine."

Research highlights include:

Oral Presentation (1506): A technology-enabled clinical trial program’s impact on patient screening and trial enrollment in 2024
Date/Time: Monday, June 2 from 3:00 PM–6:00 PM CDT
Overview: The TIME network utilized algorithmic screening technology combined with nurse match review to screen over 1.28 million patients for clinical trials in 2024, resulting in 573 total consents – an average of 1.57 consents per day. The network’s programmatic screening at scale, Tempus nurse review, and rapid activation processes helps increase patient access to trials.
Poster Presentation (213/3544): Circulating tumor DNA (ctDNA) dynamics in liver-limited metastatic colorectal cancer (mCRC) patients resected after first-line systemic treatment
Date/Time: Saturday, May 31 from 9:00 AM–12:00 PM CDT
Overview: Tempus xM, a tumor-naive test, serves as a prognostic tool for monitoring disease recurrence in resected liver-limited mCRC patients treated with upfront systemic therapy. xM demonstrates strong performance in predicting clinical recurrence and relapse-free survival following surgery.
Poster Presentation (499/11160): Evaluation of large language model (LLM)-based clinical abstraction of Electronic Health Records (EHRs) for Non-Small Cell Lung Cancer (NSCLC) patients
Date/Time: Saturday, May 31 from 1:30 PM–4:30 PM CDT
Overview: LLMs show promise for improving abstraction efficiency, converting clinical data from unstructured EHRs into a structured format suitable for analysis. Tempus utilized a two-stage LLM system to abstract critical clinical data of NSCLC patients, achieving high agreement with human abstractors across various data domains.
Poster Presentation (148/6532): Detection of KMT2A Partial Tandem Duplication (PTD) in AML by Whole Genome Sequencing (WGS): Addressing Limitations of Traditional Techniques in the Era of Revumenib Approval
Date/Time: Sunday, June 1 at 9:00 AM–12:00 PM CDT
Overview: Tempus xH, a whole genome sequencing assay for hematologic malignancies, enables highly sensitive detection of KMT2A-PTDs in AML—unlocking access to targeted therapies like revumenib. xH helps identify patients who may benefit from emerging treatments and equips clinicians with the insights they need.
Poster Presentation (20/2558): A molecular biomarker for longitudinal monitoring of therapeutic efficacy in a real-world cohort of advanced solid tumors treated with immune checkpoint inhibitors
Date/Time: Sunday, June 1 at 1:30 PM–4:30 PM CDT
Overview: Tempus xM, a tumor-naive test, monitors treatment response by tracking ctDNA dynamics over time. Patients classified as a molecular non-responder at at least one timepoint while on immunotherapy had worse overall survival than molecular responders or patients with no ctDNA detected, highlighting the value of xM molecular response monitoring as a tool to guide ICI treatment decisions.

Artera Presenting Validation Data at 2025 ASCO Annual Meeting Highlighting How Multimodal AI Platform (MMAI) is Advancing Personalized Cancer Care

On May 30, 2025 Artera, the developer of multimodal artificial intelligence (MMAI)-based prognostic and predictive cancer tests, reported the presentation of two new abstracts at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, including an oral presentation selected for Best of ASCO (Free ASCO Whitepaper) 2025, an honor reserved for studies with the greatest potential to shape the future of cancer care (Press release, Artera, MAY 30, 2025, View Source [SID1234653534]).

The featured oral presentation showcases the first validated MMAI algorithm—used in the ArteraAI Prostate Test—to identify high-risk, non-metastatic prostate cancer patients who are likely to benefit from adding androgen receptor pathway inhibitors (ARPIs) to standard therapy. The STAMPEDE trial helped to establish ARPIs as the standard of care treatment for high-risk patients, but adoption of ARPIs has been uneven, likely due to concerns over side effects and follow-up care.

The study, conducted as part of the STAMPEDE trial, evaluated the addition of ARPIs—specifically abiraterone acetate + prednisolone—to standard androgen deprivation therapy (ADT) and radiation. Artera’s model identified that only 25% of high-risk patients derived meaningful benefit from ARPI intensification, suggesting the opportunity to spare up to 75% of this cohort from unnecessary toxicities.

"This data helps answer one of the most critical questions in cancer care: which patients will benefit from added treatment, and which will not," said Nick James, MD, PhD, Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research, London, and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust. While traditional tests flag patients at risk of poor outcomes, they don’t personalize treatment decisions. Our collaboration with Artera allows us to uncover patterns invisible to the human eye and optimize treatments like never before. The AI tool allows us to connect beneficial treatments to the patient, while sparing those who may suffer unnecessary side effects, or even premature death, if they receive ARPIs they don’t need."

In addition to the oral presentation, Artera will also present a poster featuring external validation of its MMAI platform in men who have undergone radical prostatectomy (RP) for localized prostate cancer. The study demonstrates that the RP MMAI model is an independent prognostic tool for predicting biochemical recurrence (BCR) and long-term outcomes, even when controlling for clinical risk models. Artera’s solution works with routine pathology and clinical data and does not require extra tissue or complex molecular testing, making it broadly scalable, cost-effective, and faster to implement.

"We are proud to see Artera’s MMAI platform recognized with two abstracts at ASCO (Free ASCO Whitepaper), including an oral presentation selected for Best of ASCO (Free ASCO Whitepaper)," said Timothy Showalter, Chief Medical Officer of Artera. "These studies reinforce our commitment to the rigorous clinical validation of the ArteraAI Prostate Test and our broader MMAI platform. Together, they reflect our mission to empower clinicians and patients with personalized, actionable insights that support confident, shared decision-making in prostate cancer care."

The studies presented by Artera add to the growing body of evidence that its MMAI platform can inform real-time clinical decisions and bring personalized cancer care to broader patient populations. For more information on Artera, visit Artera.ai.

Presentations at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting include:

Oral Presentation: Multimodal artificial intelligence (MMAI) model to identify benefit from 2nd-generation androgen receptor pathway inhibitors (ARPI) in high-risk non-metastatic prostate cancer patients from STAMPEDE.
Abstract Number: 5001
Session Type and Title: Oral Session – Genitourinary Cancer—Prostate, Testicular, and Penile
Date and Time: Tuesday, June 3rd at 9:45 a.m. CT

Poster Presentation: External validation of a pathology-based multimodal artificial intelligence biomarker for predicting prostate cancer outcomes after prostatectomy.
Abstract Number: 5106
Session Type and Title: Poster Session – Genitourinary Cancer—Prostate, Testicular, and Penile
Date and Time: Monday, June 2nd at 9:00 a.m. CT