FORE Biotherapeutics Raises $38 Million in Series D-2 Financing for the Continued Advancement of Plixorafenib

On May 22, 2025 FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, reported a $38 million Series D-2 financing (Press release, Fore Biotherapeutics, MAY 22, 2025, View Source [SID1234653303]). For this initial close of the Series D-2, leading healthcare dedicated investors participated, including SR One, Medicxi, OrbiMed, HBM Healthcare Investments, Wellington Management, Novartis Venture Fund, Cormorant Asset Management, and 3B Future Health Fund. This $38 million adds to the $75 million raised as part of the earlier Series D and D-1 financings, for an aggregate total to date of $113 million for this Series D financing.

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"At SR One, our mission is to invest in companies that we believe have the ability to innovate and advance transformational new therapies in areas of high unmet medical need," said Simeon George, M.D., Chief Executive Officer and Managing Partner at SR One. "Fore Bio is focused on resetting the standard in BRAF driven tumors with a potential first in class paradox breaker with compelling early clinical data that support the potential of plixorafenib monotherapy to address the well-known treatment gaps oncologists face with first- and second-generation BRAF inhibitors. We are impressed with the team’s progress to date, excited about the multiple near term data readouts, and are proud to support the continued advancement of plixorafenib."

"This financing is a testament to the hard work of our team in developing plixorafenib, a differentiated, rationally designed BRAF inhibitor for both V600 and non V600 mutations that has already generated compelling data to date. We believe plixorafenib has the potential to overcome the limitations of currently available BRAF inhibitors, representing a multi-billion-dollar market opportunity," said William Hinshaw, Chief Executive Officer of Fore. "We are grateful for the continued support of this highly regarded investor syndicate and their confidence in both the Fore Bio team and plixorafenib. With their backing, we are well positioned to continue our capitally efficient execution and make significant strides in delivering the ongoing FORTE Master Protocol as we look to multiple anticipated interim analyses and clinical data supporting potential registration under the accelerated approval pathway with FDA submissions potentially at the end of next year."

Proceeds from the financing will be used to advance the registration-intended FORTE Master Protocol, a global Phase 2 clinical trial which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are BRAF V600 Recurrent Primary Central Nervous System (CNS) Tumors, Rare BRAF V600 Mutated Solid Tumors and Solid Tumors with BRAF Fusions.

2025 Strategic Objectives and Anticipated Milestones

Fore Bio is anticipating interim analyses to occur in 2025 across three monotherapy indications being evaluated in the FORTE Master Protocol:

BRAF V600 Primary Recurrent CNS Tumors: In this cohort, up to approximately 50 patients with BRAF V600 primary recurrent CNS tumors will be treated with plixorafenib. The primary endpoints of the study are overall response rate (ORR) and median duration of response (mDOR). An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the third quarter of 2025. Pending a positive recommendation from the data monitoring committee, topline data from this trial would be anticipated in the second half of 2026. The company anticipates that this trial, with sufficient demonstration of safety and efficacy, would enable the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) under the Accelerated Approval pathway. In a previously conducted Phase 1/2 study of patients with MAPK inhibitor naïve BRAF V600 primary recurrent CNS tumors (n=9), plixorafenib monotherapy demonstrated a 67% ORR and a mDOR of 13.9 months, along with a favorable tolerability profile.

Rare BRAF V600 Mutated Solid Tumors: In this cohort, up to approximately 75 patients with rare BRAF V600 mutated solid tumors will be treated with plixorafenib. The primary endpoints of the study are ORR and median duration of response mDOR. An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. In a previously conducted Phase 1/2 study of patients with MAPK inhibitor naïve BRAF V600 mutated solid tumors (n=24), plixorafenib monotherapy demonstrated a 42% ORR and a mDOR of 17.8 months, along with a favorable tolerability profile.

Advanced Solid Tumors with BRAF Fusions: In this cohort, up to approximately 75 patients with advanced solid tumors with non-V600 BRAF fusions will be treated with plixorafenib. The primary endpoints of the study are ORR and median duration of response mDOR. An interim efficacy analysis from the first 25 evaluable patients is anticipated to be conducted in the fourth quarter of 2025. In a previously conducted Phase 1/2 study of adults with advanced solid tumors with BRAF fusions (n=14), plixorafenib monotherapy results in one complete response (with a DOR of 67.4 months), one partial response and 7 stable disease, along with a favorable tolerability profile.

Recent and Upcoming Medical Meeting Presentations

AACR 2025: In April 2025, Fore presented new circulating tumor DNA (ctDNA) results from a previously completed plixorafenib clinical trial and presented the basket study design for the ongoing global Phase 2 FORTE clinical trial at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025. Results from the plasma ctDNA analysis of over 70 plixorafenib-treated patients demonstrated a high concordance between changes in ctDNA and tissue biopsy of several BRAF mutations. The correspondence shown between changes in ctDNA and tumor size across tumor types suggests that ctDNA may be a viable surrogate marker for monitoring disease. Compared to acquired mutations driving resistance to early generation BRAF inhibitors, no new mutations in MAPK pathway genes were found following plixorafenib treatment, supporting the dimer–breaker property and novel mechanism of action of plixorafenib from the early generation BRAF inhibitors.

ASCO 2025: At the upcoming 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 30 – June 3 in Chicago, Fore will present the master protocol design of the ongoing global Phase 2 FORTE clinical trial.

Exelixis Announces Encouraging Results from Phase 1b/2 STELLAR-002 Trial Evaluating Zanzalintinib in Combination with Immune Checkpoint Inhibitors in Advanced Kidney Cancer at ASCO 2025

On May 22, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported results from an expansion cohort of the phase 1b/2 STELLAR-002 trial evaluating zanzalintinib in combination with either nivolumab (Opdivo) or a fixed-dose combination of nivolumab and relatlimab (Opdualag) in patients with previously untreated advanced clear cell renal cell carcinoma (RCC) (Press release, Exelixis, MAY 22, 2025, View Source [SID1234653302]). These findings, as well as data from multiple dose-escalation cohorts from STELLAR-002, will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"We are pleased to present these preliminary findings from the phase 1b/2 STELLAR-002 study, including early signs of promising activity for zanzalintinib in combination with immune checkpoint inhibitors," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "Data emerging from this ongoing study are important to help inform further evaluation of zanzalintinib-based regimens in advanced solid tumors, including renal cell carcinoma."

Abstract 4515: Zanzalintinib + Nivolumab ± Relatlimab in Patients with Previously Untreated Clear Cell Renal Cell Carcinoma: Results from an Expansion Cohort of the Phase 1b STELLAR-002 Study
Lead Author: Jad Chahoud, M.D., M.P.H., Moffitt Cancer Center, Tampa, Fla., USA
Session Title: Genitourinary Cancer—Kidney and Bladder
Saturday, May 31, 1:15-2:45 p.m. CDT

This expansion cohort of STELLAR-002 included patients with advanced clear cell RCC who received zanzalintinib in combination with either nivolumab (n=40) or fixed-dose nivolumab and relatlimab (n=40) in two non-randomized treatment arms. Patients had unresectable advanced or metastatic disease for which they received no prior systemic therapy. Intermediate- or poor-risk disease, per the International Metastatic RCC Database Consortium, accounted for 75% of patients receiving zanzalintinib in combination with nivolumab and 70% of patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab.

At a median follow-up of 20.1 months for those receiving zanzalintinib in combination with nivolumab and 15.9 months for those receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab, the objective response rates were 63% (95% confidence interval [CI]: 46-77%) and 40% (95% CI: 25-57%), respectively. Disease control rates were 90% (95% CI: 76-97%) for both arms. The 12-month duration of response was 73.4% (95% CI: 50.0-87.1%) and 74.1% (95% CI: 39.1-90.9%), respectively. Median progression-free survival was 18.5 months (95% CI: 9.5 months-not estimable [NE]) and 13.0 months (95% CI: 7.4 months-NE), respectively.

"While significant progress has been made in advanced clear cell renal cell carcinoma, many patients still experience disease progression, and more effective therapies earlier in the treatment landscape are needed," said Jad Chahoud, M.D., M.P.H., Associate Member, Department of Genitourinary Oncology and Medical Director of the Inpatient/Outpatient (IPOP) service at Moffitt Cancer Center in Tampa, Fla., who is presenting the findings. "The high rate of durable responses and long progression-free survival observed for zanzalintinib in combination with nivolumab are encouraging and support further evaluation of this regimen."

Treatment-emergent adverse events (TEAEs) of any grade were reported in all patients. Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with nivolumab included hypertension (n=13), diarrhea (n=6), aspartate aminotransferase increase (n=5), alanine aminotransferase increase (n=5) and palmar-plantar erythrodysesthesia (n=4). Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab included hypertension (n=6), rash (n=6), lipase increase (n=4) and pulmonary embolism (n=4). There were two grade 5 TEAEs in each arm; none were considered related to study treatment. Three patients (8%) in the zanzalintinib in combination with nivolumab arm and eight patients (20%) in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab arm discontinued all study drugs for treatment-related AEs as assessed by investigator.

Abstract 3101: Zanzalintinib + Nivolumab ± Relatlimab in Patients with Advanced Solid Tumors: Results from Two Dose-Escalation Cohorts of the Phase 1b STELLAR 002 Study
Lead Author: Benjamin Garmezy, M.D., Sarah Cannon Research Institute, Nashville, Tenn., USA
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Monday, June 2, 1:30-4:30 p.m. CDT

This analysis of STELLAR-002 included multiple cohorts of patients with advanced solid tumors who received zanzalintinib 100 mg in combination with nivolumab (n=19); zanzalintinib 60 mg in combination with fixed-dose nivolumab and relatlimab (n=24); or zanzalintinib 100 mg in combination with fixed-dose nivolumab and relatlimab (n=25). The most common cancer types for those receiving zanzalintinib in combination with nivolumab were colorectal and prostate cancers, followed by lung cancer and RCC. The most common tumor types in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab cohorts were RCC, followed by prostate cancer, melanoma and colorectal cancer.

The findings showed that the toxicity profile of these combinations was manageable and consistent with each monotherapy agent. Preliminary safety, efficacy and pharmacokinetic results supported selection of the 100 mg dose for zanzalintinib for the ongoing expansion cohorts.

About STELLAR-002
STELLAR-002 (NCT05176483) is a global, open-label phase 1b/2 study of zanzalintinib as a single agent or in combination with nivolumab, fixed-dose nivolumab and relatlimab or nivolumab and ipilimumab in advanced solid tumors. The objective of the study is to evaluate the safety, tolerability and efficacy of zanzalintinib alone and in these combinations. The trial is divided into two parts: a dose-escalation stage and an expansion cohort stage. Expansion cohorts include patients with clear cell RCC, non-clear cell RCC, castration-resistant prostate cancer, urothelial carcinoma, hepatocellular carcinoma, non-small cell lung cancer, colorectal cancer and head and neck squamous cell carcinoma. Exelixis is sponsoring STELLAR-002, and Bristol Myers Squibb is providing nivolumab, ipilimumab and a fixed-dose combination of nivolumab and relatlimab for use in the trial. More information about the trial is available at ClinicalTrials.gov.

About Zanzalintinib
Zanzalintinib is a third-generation oral tyrosine kinase inhibitor that inhibits the activity of receptor tyrosine kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including neuroendocrine tumors, genitourinary, colorectal and head and neck cancers.

About RCC
Kidney cancer is among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Nearly 81,000 Americans will be diagnosed with kidney cancer in 2025.1 Clear cell RCC is the most common type of kidney cancer in adults.2 Non-clear cell RCC represents about 25% of RCC cases, with fewer treatment options available and poorer outcomes compared with clear cell RCC.3 Advanced or metastatic RCC occurs when the cancer has spread beyond the kidney.4 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 18%.5 In 2025, approximately 33,700 patients with advanced kidney cancer will require systemic therapy in the U.S., with over 21,400 patients receiving first-line treatment.

Exelixis to Webcast Fireside Chats as Part of Upcoming Investor Conferences in May and June

On May 22, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported that company management will participate in fireside chats at the following investor conferences in May and June (Press release, Exelixis, MAY 22, 2025, View Source [SID1234653301]):

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TD Cowen 6th Annual Oncology Innovation Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper): Exelixis is scheduled to present virtually at 2:30 p.m. ET / 11:30 a.m. PT on Tuesday, May 27.
William Blair 45th Annual Growth Stock Conference: Exelixis is scheduled to present at 11:00 a.m. ET / 10:00 a.m. CT / 8:00 a.m. PT on Tuesday, June 3 in Chicago.
Jefferies Global Healthcare Conference 2025: Exelixis is scheduled to present at 7:35 a.m. ET / 4:35 a.m. PT on Wednesday, June 4 in New York City.

To access the webcast links, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. Replays will also be available at the same location for at least 30 days.

Exact Sciences Highlights Innovations in Early Cancer Detection and Precision Oncology at ASCO 2025

On May 22, 2025 Exact Sciences Corp. (NASDAQ: EXAS), a leading provider of cancer screening and diagnostic tests, reported it will present ten abstracts at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 30–June 3, 2025, in Chicago, Ill (Press release, Exact Sciences, MAY 22, 2025, View Source [SID1234653300]). Presentations include new data on the Oncodetect molecular residual disease (MRD) test, multi-cancer early detection (MCED) testing, the Oncotype DX Breast Recurrence Score test, and the Cologuard test that underscore Exact Sciences’ expanding portfolio and commitment to advancing care through scientific excellence.

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"The data Exact Sciences will present at ASCO (Free ASCO Whitepaper) 2025 reflect the scientific rigor and clinical significance of our expanding portfolio and pipeline," said Dr. Rick Baehner, MD, chief medical officer, Precision Oncology at Exact Sciences. "From MRD to MCED to CRC screening, we are advancing evidence-based innovations that help empower providers and deliver crucial answers to patients. Every study, partnership, and data point move us closer to a future where cancer is detected earlier and treated with greater precision."

Real-world evidence supporting the Cologuard test continues to grow, with ongoing research into repeat screening. New data from prominent experts and research groups reinforce the Oncotype DX test as a trusted, evidence-backed tool, further affirming its role as the standard of care for predicting chemotherapy benefit for breast cancer patients. Building on more than a decade of experience with Cologuard and 20 years of leadership with the Oncotype DX test, Exact Sciences continues to advance the future of precision oncology and multi-cancer screening.

New Data and Continuous Evidence Generation Underscore the Oncodetect Test’s Power to Detect Cancer Recurrence. Data from the Beta-CORRECT study further strengthens the clinical foundation of the Oncodetect test, confirming its role in helping guide treatment decisions and surveillance strategies for patients with stage II–IV colorectal cancer1. Expanding on this evidence to multiple solid tumor types, Exact Sciences and Flatiron Health continue enrollment in a multi-year, prospective study evaluating how MRD testing can improve cancer monitoring and treatment decisions in community care settings.

New Data Support Promise of MCED as Exact Sciences Prepares for LDT Launch. A modeling study found annual MCED testing could reduce late-stage cancer incidence by more than 40% and mortality by up to 18% in high-risk groups2. Additionally, the Falcon registry, a large, prospective real-world study of Exact Sciences’ MCED test, will track 25,000 participants against a 50,000-person standard-care cohort to assess adoption, outcomes, and patient experience. These findings come as Exact Sciences prepares to launch Cancerguard EX, its MCED lab-developed test (LDT), in the second half of the year, marking a significant step in expanding access to earlier cancer detection.

Exact Sciences abstracts at ASCO (Free ASCO Whitepaper) include:

Precision Oncology

The Association of Circulating Tumor DNA (ctDNA) with Recurrence in Patients with Stage II-IV Colorectal Cancer: The ꞵ-CORRECT Study
Saturday, May 31, 2025, from 9:00 AM to 12:00 PM CT
Abstract number: 3590
Molecular Residual Disease (MRD) in Solid Tumors
Monday, June 2, 2025, from 9:00 AM to 12:00 PM CT
Abstract number: TPS3186
Enhancing Recurrence Detection in Stage III Colorectal Cancer Patients Through Molecular Residual Disease Test-guided Surveillance: A Modeling Study
Abstract number: e15600
Patient outcomes in WSG-ADAPT according to NATALEE and MonarchE risk criteria
Monday, June 2, 2025, from 9:00 AM to 12:00 PM CT
Abstract number: 601
Screening

Adherence to repeat screening for colorectal cancer using the multi-target stool DNA test: Real-world analysis of patients from Federally Qualified Health Centers
Saturday, May 31, 2025, from 9:00 AM to 12:00 PM CT
Abstract number: 3630
A decade of progress: Trends in 5-year survival across 17 cancer types
Abstract number: e23262
The potential of multi-cancer early detection screening in reducing cancer incidence and mortality in high-risk groups: A modeling study
Saturday, May 31, 2025, from 1:30 PM to 5:30 PM CT
Abstract number: 10542
Falcon – Exact Sciences’ multi-cancer early detection (MCED) real-world evidence (RWE) registry
Saturday, May 31, 2025, from 1:30 PM to 5:30 PM CT
Abstract number: TPS11189
Evaluation of plasma methylated DNA markers for detection HPV-positive oropharyngeal squamous cell carcinoma: a case control study
Monday, June 2, 2025, from 9:00 AM to 12:00 PM CT
Abstract number: 6057
Feasibility of vaginal tampons versus vaginal swabs in the collection of vaginal fluid for endometrial cancer testing
Abstract number: e17617

Lilly announces details of presentations at 2025 American Society of Clinical Oncology (ASCO) Annual Meeting

On May 22, 2025 Eli Lilly and Company (NYSE: LLY) reported that data from studies of imlunestrant, an investigational oral selective estrogen receptor degrader (SERD), olomorasib, an investigational KRAS G12C inhibitor, LY4170156, an investigational antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα) and Verzenio (abemaciclib; a CDK4/6 inhibitor) will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 30 – June 3 in Chicago (Press release, Eli Lilly, MAY 22, 2025, View Source [SID1234653299]).

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Presentation Highlights
Imlunestrant (investigational oral SERD)
In an oral presentation, Lilly will share patient-reported outcomes (PROs) from the Phase 3 EMBER-3 trial in patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC), and a poster presentation will feature expanded EMBER-3 safety analyses.

Olomorasib (investigational KRAS G12C inhibitor):
In two oral presentations, Lilly will report updated results from a Phase 1/2 study of olomorasib, a potent and highly selective second-generation inhibitor of KRAS G12C with preliminary evidence of CNS activity, in combination with pembrolizumab in patients with KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC) and in combination with cetuximab in patients with KRAS G12C-mutant colorectal cancer (CRC). The submitted abstracts utilized a November 13, 2024 data cut-off date, and the presentations will utilize a January 15, 2025 data cut-off date.

LY4170156 (investigational ADC targeting FRα):
In a poster presentation, Lilly will report initial results from the multicenter, open-label, first-in-human Phase 1a/1b study of LY4170156 in patients with platinum-resistant ovarian cancer (PROC). LY4170156 is an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker. The submitted abstract utilized a November 27, 2024 data cut-off date, and the poster will utilize a March 9, 2025 data cut-off date.

A full list of abstract titles and viewing details are listed below:

Imlunestrant (investigational oral SERD):
Presentation Title: Patient-reported outcomes (PROs) in patients with ER+, HER2- advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant + abemaciclib: Results from the phase III EMBER-3 trial
Abstract Number: 1001
Session Date & Time: Saturday, May 31, 1:15-4:15 p.m. CDT
Session Title: Breast Cancer – Metastatic
Location: Hall B1 | Live Stream
Presenter: Giuseppe Curigliano

Presentation Title: Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): Safety analyses from the phase III EMBER-3 trial
Abstract Number: 1060
Session Date & Time: Monday, June 2, 9 a.m.-12 p.m. CDT
Session Title: Breast Cancer – Metastatic
Location: Hall A – Posters and Exhibits | On Demand
Presenter: Joyce O’Shaughnessy

Olomorasib (investigational KRAS G12C inhibitor):
Presentation Title: Efficacy and safety of olomorasib, a second-generation KRAS G12C inhibitor, plus cetuximab in KRAS G12C-mutant advanced colorectal cancer
Abstract Number: 3507
Session Date & Time: Friday, May 30, 2:45-5:45 p.m. CDT
Session Title: Gastrointestinal Cancer – Colorectal and Anal
Location: Arie Crown Theater | Live Stream
Presenter: Antoine Hollebecque

Presentation Title: Safety and efficacy of olomorasib + immunotherapy in first-line treatment of patients with KRAS G12C-mutant advanced NSCLC: Update from the LOXO-RAS-20001 trial
Abstract Number: 8519
Session Date & Time: Monday, June 2, 8-9:40 a.m. CDT
Session Title: Lung Cancer – Non-Small Cell Metastatic
Location: Arie Crown Theater | Live Stream
Presenter: Alexander I. Spira

LY4170156 (investigational ADC targeting FRα):
Presentation Title: Initial results from a first-in-human phase 1 study of LY4170156, an ADC targeting folate receptor alpha (FRα), in advanced ovarian cancer and other solid tumors
Abstract Number: 3023
Session Date & Time: Monday, June 2, 1:30-4:30 p.m. CDT
Session Title: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Location: Hall A – Posters and Exhibits | On Demand
Presenter: Isabelle Ray-Coquard

Verzenio (abemaciclib):
Presentation Title: Impact of body mass index (BMI) on efficacy and safety of abemaciclib in breast cancer patients (pts) treated in the monarchE trial
Abstract Number: 520
Session Date & Time: Monday, June 2, 9 a.m.-12 p.m. CDT
Session Title: Breast Cancer – Local/Regional/Adjuvant
Location: Hall A – Posters and Exhibits | On Demand
Presenter: Christine Desmedt

For more information on Lilly’s Oncology pipeline click here.

About Imlunestrant
Imlunestrant is an investigational, brain-penetrant, oral selective estrogen receptor degrader (SERD), that delivers continuous ER inhibition, including in ESR1-mutant cancers. The estrogen receptor (ER) is the key therapeutic target for patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Novel degraders of ER may overcome endocrine therapy resistance while providing consistent oral pharmacology and convenience of administration. Imlunestrant is currently being studied as a treatment for advanced breast cancer and as an adjuvant treatment in early breast cancer, including: NCT04975308, NCT05514054, NCT04188548, NCT05307705.

About Olomorasib
Olomorasib (LY3537982) is an investigational, oral, potent, and highly selective second-generation inhibitor of the KRAS G12C protein. KRAS is the most common oncogene across all tumor types, and KRAS G12C mutations occur in 13% of patients with non-small cell lung cancer (NSCLC), and 1-3% of patients with other solid tumors.1 Olomorasib is a highly potent covalent inhibitor with potential for greater than 90% target occupancy, which may allow for safer combinations with less toxicity.2

Olomorasib is currently being studied in KRAS G12C-mutated cancers in combination with pembrolizumab with or without chemotherapy for first-line treatment of advanced NSCLC, in combination with immunotherapy for the treatment of resected and unresectable NSCLC, and as monotherapy and in combinations in other advanced solid tumors, including: NCT06119581, NCT06890598, and NCT04956640.

About LY4170156
LY4170156 is an investigational, next-generation antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). FRα is a cell-surface glycoprotein encoded by the gene FOLR1 that binds to the essential nutrients folic acid and reduced folates, bringing them into cells to facilitate cell division and growth.3,4 FRα is overexpressed in many solid tumors such as ovarian, non-small cell lung, and colorectal cancers.3,5,6

LY4170156 was designed to target FRα across expression levels with an improved therapeutic index. LY4170156 is composed of a Fc-silent, FRα specific humanized monoclonal antibody, linked to exatecan, a topoisomerase-I inhibitor, via a proprietary cleavable polysarcosine linker. LY4170156 is currently being studied in patients with ovarian cancer as well as other FRα-expressing solid tumors, NCT06400472.

About Verzenio (abemaciclib)
Verzenio (abemaciclib) is approved to treat people with certain HR+, HER2- breast cancers in the adjuvant and advanced or metastatic settings.

Verzenio is an oral tablet taken twice daily and available in strengths of 50 mg, 100 mg, 150 mg, and 200 mg. Discovered and developed by Lilly researchers, Verzenio was first approved in 2017 and is currently authorized for use in more than 90 counties around the world. For full details on indicated uses of Verzenio in HR+, HER2- breast cancer, please see full Prescribing Information, available at www.Verzenio.com.

INDICATIONS FOR VERZENIO

VERZENIO is a kinase inhibitor indicated:

in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence.
in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.
in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
IMPORTANT SAFETY INFORMATION FOR VERZENIO (abemaciclib)

Severe diarrhea associated with dehydration and infection occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, diarrhea occurred in 81 to 90% of patients who received Verzenio. Grade 3 diarrhea occurred in 8 to 20% of patients receiving Verzenio. Most patients experienced diarrhea during the first month of Verzenio treatment. The median time to onset of the first diarrhea event ranged from 6 to 8 days; and the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to 11 days and 5 to 8 days, respectively. Across trials, 19 to 26% of patients with diarrhea required a Verzenio dose interruption and 13 to 23% required a dose reduction.

Instruct patients to start antidiarrheal therapy, such as loperamide, at the first sign of loose stools, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.

Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, neutropenia occurred in 37 to 46% of patients receiving Verzenio. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 19 to 32% of patients receiving Verzenio. Across trials, the median time to first episode of Grade ≥3 neutropenia ranged from 29 to 33 days, and the median duration of Grade ≥3 neutropenia ranged from 11 to 16 days. Febrile neutropenia has been reported in <1% of patients exposed to Verzenio across trials. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider.

Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis can occur in patients treated with Verzenio and other CDK4/6 inhibitors. In Verzenio-treated patients in EBC (monarchE), 3% of patients experienced ILD or pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality (0.1%). In Verzenio-treated patients in MBC (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD or pneumonitis have been observed in the postmarketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD or pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations. Dose interruption or dose reduction is recommended in patients who develop persistent or recurrent Grade 2 ILD or pneumonitis. Permanently discontinue Verzenio in all patients with Grade 3 or 4 ILD or pneumonitis.

Grade ≥3 increases in alanine aminotransferase (ALT) (2 to 6%) and aspartate aminotransferase (AST) (2 to 3%) were reported in patients receiving Verzenio. Across three clinical trials in 3559 patients (monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade ≥3 ALT increases ranged from 57 to 87 days and the median time to resolution to Grade <3 was 13 to 14 days. The median time to onset of Grade ≥3 AST increases ranged from 71 to 185 days and the median time to resolution to Grade <3 ranged from 11 to 15 days.

Monitor liver function tests (LFTs) prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or any Grade 3 or 4 hepatic transaminase elevation.

Venous thromboembolic events (VTE) were reported in 2 to 5% of patients across three clinical trials in 3559 patients treated with Verzenio (monarchE, MONARCH 2, MONARCH 3). VTE included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. In clinical trials, deaths due to VTE have been reported in patients treated with Verzenio.

Verzenio has not been studied in patients with early breast cancer who had a history of VTE. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate. Dose interruption is recommended for EBC patients with any grade VTE and for MBC patients with a Grade 3 or 4 VTE.

Verzenio can cause fetal harm when administered to a pregnant woman, based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for 3 weeks after the last dose. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥10%) observed in monarchE for Verzenio plus tamoxifen or an aromatase inhibitor vs tamoxifen or an aromatase inhibitor, with a difference between arms of ≥2%, were diarrhea (84% vs 9%), infections (51% vs 39%), neutropenia (46% vs 6%), fatigue (41% vs 18%), leukopenia (38% vs 7%), nausea (30% vs 9%), anemia (24% vs 4%), headache (20% vs 15%), vomiting (18% vs 4.6%), stomatitis (14% vs 5%), lymphopenia (14% vs 3%), thrombocytopenia (13% vs 2%), decreased appetite (12% vs 2.4%), ALT increased (12% vs 6%), AST increased (12% vs 5%), dizziness (11% vs 7%), rash (11% vs 4.5%), and alopecia (11% vs 2.7 %).

The most frequently reported ≥5% Grade 3 or 4 adverse reaction that occurred in the Verzenio arm vs the tamoxifen or an aromatase inhibitor arm of monarchE were neutropenia (19.6% vs 1%), leukopenia (11% vs <1%), diarrhea (8% vs 0.2%), and lymphopenia (5% vs <1%).

Lab abnormalities (all grades; Grade 3 or 4) for monarchE in ≥10% for Verzenio plus tamoxifen or an aromatase inhibitor with a difference between arms of ≥2% were increased serum creatinine (99% vs 91%; .5% vs <.1%), decreased white blood cells (89% vs 28%; 19.1% vs 1.1%), decreased neutrophil count (84% vs 23%; 18.7% vs 1.9%), anemia (68% vs 17%; 1% vs .1%), decreased lymphocyte count (59% vs 24%; 13.2 % vs 2.5%), decreased platelet count (37% vs 10%; .9% vs .2%), increased ALT (37% vs 24%; 2.6% vs 1.2%), increased AST (31% vs 18%; 1.6% vs .9%), and hypokalemia (11% vs 3.8%; 1.3% vs 0.2%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole vs anastrozole or letrozole, with a difference between arms of ≥2%, were diarrhea (81% vs 30%), fatigue (40% vs 32%), neutropenia (41% vs 2%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3.1%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 1%), diarrhea (9% vs 1.2%), leukopenia (7% vs <1%)), increased ALT (6% vs 2%), and anemia (6% vs 1%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥10% for Verzenio plus anastrozole or letrozole with a difference between arms of ≥2% were increased serum creatinine (98% vs 84%; 2.2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs 0.6%), anemia (82% vs 28%; 1.6% vs 0%), decreased neutrophil count (80% vs 21%; 21.9% vs 2.6%), decreased lymphocyte count (53% vs 26%; 7.6% vs 1.9%), decreased platelet count (36% vs 12%; 1.9% vs 0.6%), increased ALT (48% vs 25%; 6.6% vs 1.9%), and increased AST (37% vs 23%; 3.8% vs 0.6%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 2 for Verzenio plus fulvestrant vs fulvestrant, with a difference between arms of ≥2%, were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 2.7%), thrombocytopenia (16% vs 3%), alopecia (16% vs 1.8%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs <1%), rash (11% vs 4.5%), pyrexia (11% vs 6%), and weight decreased (10% vs 2.2%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (25% vs 1%), diarrhea (13% vs 0.4%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (5.7% vs 3.5%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥10% for Verzenio plus fulvestrant with a difference between arms of ≥2% were increased serum creatinine (98% vs 74%; 1.2% vs 0%), decreased white blood cells (90% vs 33%; 23.7% vs .9%), decreased neutrophil count (87% vs 30%; 32.5% vs 4.2%), anemia (84% vs 34%; 2.6% vs .5%), decreased lymphocyte count (63% vs 32%; 12.2% vs 1.8%), decreased platelet count (53% vs 15%; 2.1% vs 0%), increased ALT (41% vs 32%; 4.6% vs 1.4%), and increased AST (37% vs 25%; 3.9% vs 4.2%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), constipation (17%), leukopenia (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were diarrhea (20%), neutropenia (24%), fatigue (13%), and leukopenia (5%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (99%; .8%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 26.6%), anemia (69%; 0%), decreased lymphocyte count (42%; 13.8%), decreased platelet count (41%; 2.3%), increased ALT (31%; 3.1%), and increased AST (30%; 3.8%).

Strong and moderate CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other than ketoconazole. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Verzenio dose in 50 mg decrements. Patients should avoid grapefruit products.

Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents. Coadministration of strong or moderate CYP3A inducers decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity.

With severe hepatic impairment (Child-Pugh C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr <30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min).

Please see full Prescribing Information and Patient Information for Verzenio.