On May 15, 2024 Galapagos NV (Euronext & NASDAQ: GLPG) and Blood Centers of America (BCA) reported that they have entered into a strategic collaboration for the decentralized manufacturing of Galapagos’ CAR-T cell therapies through BCA’s network in the U.S (Press release, Galapagos, MAY 16, 2024, View Source [SID1234643392]).

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Under the terms of the collaboration agreement, BCA will provide access to its extensive network of over 50 community blood centers in 43 states for Good Manufacturing Practice compliant manufacturing for Galapagos’ CAR-T hemato-oncology clinical program. This agreement complements existing collaborations between Galapagos and Landmark Bio and Thermo Fisher Scientific.

Galapagos will leverage BCA’s network to initiate technology transfer to multiple sites in parallel for the decentralized manufacturing of its CAR-T product candidates, close to cancer treatment centers, while also accessing apheresis capacity at BCA sites when required. In addition, BCA will play a crucial coordinating role by supporting site initiation and onboarding to accelerate Galapagos’ efforts and ensure consistent quality.

Galapagos’ innovative, decentralized manufacturing platform could address many of the limitations that currently available CAR-T production is facing. It has the potential to offer greater speed and scalability, with the delivery of fresh, fit cells with a vein-to-vein time of seven days and the possibility for greater physician control and improved patient experience.

"Our collaboration with Blood Centers of America marks a major milestone for Galapagos’ U.S. expansion by establishing centers for support of our pivotal studies, with the potential to be used for commercial introduction. Working with BCA’s extensive nationwide network allows us to efficiently scale up decentralized CAR-T therapy manufacturing across the U.S., while their established infrastructure helps us harmonize operations and access apheresis capacity," said Dr. Paul Stoffels1, CEO and Chairman of the Board of Directors of Galapagos. "This agreement complements the existing collaborations between Galapagos and Landmark Bio and Thermo Fisher Scientific and translates to a significant step forward in our aspiration to bring CAR-T therapies to more patients with a vein-to-vein time of just seven days."

"We are very pleased to partner with Galapagos in expanding their nationwide CAR-T manufacturing network," said Delisa English, BCA Board Chair. "Our decades of experience and advanced capabilities in regulatory compliant biologic processing across the U.S. will facilitate seamless technology transfer across multiple sites. We strongly believe that the combination of Galapagos’ decentralized manufacturing platform and our national cell therapy manufacturing footprint will ultimately benefit patients by providing convenient access to our local facilities for apheresis and local healthcare providers within their communities."

On May 16, 2024 Flamingo Therapeutics ("Flamingo") reported that the first patient has been dosed in an Investigator-initiated Trial (IIT) evaluating the safety and efficacy of danvatirsen in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who have relapsed or are refractory to frontline therapy (Press release, Flamingo Therapeutics, MAY 16, 2024, View Source;utm_medium=rss&utm_campaign=flamingo-therapeutics-announces-first-patient-dosed-in-investigator-initiated-trial-iit-evaluating-danvatirsen-in-phase-1-for-aml-mds-cancers [SID1234643391]). The IIT is being conducted by leading researchers at Montifore Einstein Comprehensive Cancer Center (MECCC; New York, USA) and MD Anderson Cancer Center (MDACC; Houston, USA). In the Phase 1 trial, the STAT3 inhibiting oligonucleotide danvatirsen, discovered by Ionis, will be evaluated as a monotherapy and also in combination with venetoclax, an approved frontline treatment in relapsed/refractory MDS and AML.

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AML and MDS—two related blood diseases that disproportionally impact older adults—are notoriously difficult to treat and associated with high relapse rates. Although new therapies have improved survival, treatment options remain limited, and the prognosis for the 50% of people who experience disease relapse remains poor. STAT3 protein, which danvatirsen is designed to inhibit, has been associated with worse prognosis.

"We are excited to dose the first patient and initiate a potentially ground-breaking study to evaluate a novel therapeutic strategy targeting STAT3 with danvatirsen for patients suffering from AML and MDS. This clinical trial builds upon the work that my team has done in the research lab over the past decade, and is a good example of a bench to bedside partnership between academic medical centers and industry," said Aditi Shastri, M.D., Principal Investigator of the IIT, Member of MECCC’s Stem Cell & Cancer Biology Research Program and Blood Cancer Institute, and Associate Professor of Oncology, Medicine, and Developmental and Molecular Biology at Albert Einstein College of Medicine. "I look forward to working with the Flamingo team to continue generating promising results in the ongoing clinical trial."

The IIT is being funded by a multi-year grant awarded by the US FDA Office of Orphan Products Development (OOPD) to MECCC, with Dr. Aditi Shastri as the principal investigator, and was one of only 10 grants awarded by the FDA OOPD in 2023. MD Anderson Cancer Center (MDACC) is also participating in the trial with Dr.Naval Daver being the principal investigator at the MDACC site.

"Drs. Shastri and Daver are recognized among the world’s leading experts in AML and MDS and we couldn’t be more pleased to collaborate with them, MECCC, and MDACC," said Andrew Denker, MD, PhD, Chief Medical Officer of Flamingo. "We have tremendous momentum right now with danvatirsen, with ongoing clinical programs in head and neck cancer (PEMDA-HN) and in AML/MDS. The IIT announced today is very important to broaden Flamingo’s danvatirsen clinical development program, and advance our therapy towards patients who can benefit from novel treatments."

The IIT is a Phase I study (NCT05986240) investigating danvatirsen as both a monotherapy and in combination with venetoclax in patients with AML or intermediate/high/very high risk MDS who have relapsed or are refractory to frontline therapy. The sequential dose escalation design seeks to assess safety, efficacy, pharmacokinetics and pharmacodynamics, to inform a recommended phase 2 dose and further investigations.

More information on the IIT study can be found here.

On May 16, 2024 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported its financial results for the first quarter 2024 ended March 31, 2024 (Press release, CNS Pharmaceuticals, MAY 16, 2024, View Source [SID1234643389]).

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"With topline results in our ongoing, fully enrolled Berubicin trial for GBM expected in the first half of next year, we continue to plan for success. Our commitment to our dual mission to bring meaningful treatment options to GBM patients as well as value to all stakeholders remains unwavering," commented John Climaco, Chief Executive Officer of CNS Pharmaceuticals.

Clinical Development Progress

The trial design of the Company’s potentially pivotal trial of Berubicin included a pre-planned, non-binding interim futility analysis. The Company reached the criteria required by the study protocol to conduct this interim futility analysis, which an independent DSMB is responsible for conducting. The DSMB’s charter mandated that they review the primary endpoint, Overall Survival, as well as secondary endpoints and safety data to determine whether the efficacy data for the risk-benefit profile warrants modification or discontinuation of the study. On December 18, 2023, the Company released the DSMB’s recommendation which was to continue the study without modification. Management remains blinded to the data underlying the recommendation of the DSMB.

The Company expects to report topline data from its study of Berubicin in the first half of 2025, although it is impossible to accurately predict how long patients on the study may survive, which could impact the timing of the release of topline data.

The FDA has granted CNS Pharmaceuticals Fast Track Designation for Berubicin which enables more frequent interactions with the agency for guidance on expediting the development and review process. Additionally, the Company has received Orphan Drug Designation from the FDA, which may provide seven years of marketing exclusivity upon approval of an NDA. For more information about the Berubicin clinical trial, visit clinicaltrials.gov and reference identifier NCT04762069.

Summary of Financial Results for the First Quarter 2024

The net loss for the three months ended March 31, 2024 was approximately $3.5 million compared to approximately $4.9 million for the comparable period in 2023. The change in net loss is attributable to a decrease in research organization ("CRO") expenses related to continued progress with the Company’s potentially pivotal clinical trial, as well as decreases in legal and professional fees and other expenses.

The Company reported research and development expenses of $2.4 million for the three months ended March 31, 2024 compared to approximately $3.6 million for the comparable period in 2023. The decrease in research and development expenses during the period were mainly attributed to the timing of CRO expenses related to continued progress with the Company’s potentially pivotal clinical trial.

General and administrative expense was approximately $1.1 million for the three months ended March 31, 2024 compared to approximately $1.4 million for the comparable period in 2023. The decrease in general and administrative expense was mainly attributable to decreases of approximately $118,000 in legal and professional expenses, $20,000 in insurance expenses and $58,000 in stock compensation, $39,000 in travel expenses and $29,000 in other general and administrative expenses, which were offset by increases of approximately $19,000 in marketing and advertising expenses.

As of March 31, 2024, the Company had cash of approximately $0.8 million.

On May 16, 2024 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company focused on developing innovative cancer therapies, reported that it hosted a virtual Research and Development (R&D) Day to discuss its lead asset Plinabulin, a dendritic cell (DC) maturation agent, in drug combinations to potentially address the current unmet medical needs in cancer indications where patients failed prior PD-1/PD-L1 inhibitors, as well as updates for SEED Therapeutics which focuses on target protein degradation (TPD) platform for innovative molecular glue drug discovery on May 15, 2024 (Press release, BeyondSpring Pharmaceuticals, MAY 16, 2024, View Source;utm_medium=rss&utm_campaign=beyondspring-rd-day-highlights-new-plinabulin-development-strategy-for-cancer-and-updates-for-seed-therapeutics [SID1234643388]).

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The R&D Day was led by Key Opinion Leaders (KOLs) Trevor M. Feinstein, M.D. (Piedmont Cancer Institute), Alberto Chiappori, M.D. (Moffitt Cancer Center), and Steven Lin, M.D., Ph.D. (MD Anderson Cancer Center), as well as BeyondSpring and SEED Therapeutics management.

Invited KOLs shared their latest insights on plinabulin’s durable anti-cancer benefit, mechanism-of-action (MOA), and its unique potential as an I/O combination agent with chemotherapy or radiation, in patients that have progressed on PD-1/PD-L1 therapy. Over time, plinabulin may have the potential to move into earlier lines of treatment in combination with I/O:

As a unique tubulin binder, plinabulin drives dendritic cell (DC) maturation/T-cell activation by effectively liberating the immune defense protein GEF-H1 from microtubules.
Plinabulin alone or in combination has been well-tolerated in >700 cancer patients in two positive phase 3 studies.
In a phase 3 study with EGFR wild-type 2L/3L NSCLC, the combination of plinabulin and docetaxel significantly extended OS in all subgroup analyses and doubled 2-year and 3-year OS rates compared to docetaxel alone.
In an MD Anderson phase 1 study, in combination with radiotherapy and a PD-1 inhibitor, plinabulin demonstrated its DC maturation MOA in responding patients (PR+SD) in multiple cancers that had progressed during PD-1/PD-L1 inhibitor therapy with >50% disease control rate (PR+SD). The most responding cancers include NSCLC, HNSCC and Hodgkin’s lymphoma.
PD-1/PD-L1 inhibitors have been approved in approximately 20 cancer indications with >$40 billion annual sales, and yet around 60% of patients eventually fail, leaving them with limited treatment options.
Plinabulin’s potent DC maturation effect, in combination with PD-1/PD-L1 and radiation or chemotherapy, may address unmet medical needs across numerous patient settings following progression from PD-1/PD-L1 inhibitor therapy.
Plinabulin has the potential to fill a substantial gap in cancer treatment for precisely the same patient settings that have been found elusive to other mechanisms or combinations.
"Additionally, significant headway is being made through various Investigator-Initiated Trial (IIT) studies of plinabulin at leading institutions in the U.S. and China. Preliminary results are expected to be reported in 2H 2024, that are expected to reinforce our unique MOA and lead to a transformative year for BeyondSpring. If interim clinical data from our ongoing studies further validates our unique MOA, then we will look for opportunities to extend and accelerate plinabulin’s outreach through third-party partnerships," said Dr. Lan Huang, Co-Founder, Chairman and CEO of BeyondSpring.

Following the plinabulin presentations, Dr. Lan Huang discussed how BeyondSpring’s majority-owned subsidiary, SEED Therapeutics, uses its proprietary TPD platforms to develop "molecular glues" for undruggable targets. Different from PROTAC platforms, molecular glues have the potential advantage of targeting un-ligandable proteins, including proteins without ligandable pocket, and unfolded protein, such as Tau. The SEED TPD platform referred to as RITE3, has translated the scientific breakthroughs and insights of its co-founders, including a Nobel Laureate and two Howard Hughes Medical Institute investigators, into a diversified and fast-evolving drug development pipeline:

Differentiated from other molecular glue companies, which are mainly "E3 centric", SEED’s RITE3 platform is "target centric" and uses novel E3 ligases for protein targets. With detectable weak basal interaction between selected E3 and protein target, the binder hit rates from its high throughput screening is higher.
6 internal pipeline assets and 2 partnered assets, in oncology, neurodegeneration, immunology, and virology used 5 novel E3 ligases.
SEED expects to file an IND in early 2025 for its IND Candidate oral RBM39 degrader, for the treatment of rationally selected cancer indications.
SEED R&D has a focus on the development of orally delivered molecular glues for CNS indications, with a lead internal program against Tau.
Eli Lilly is a current investor and R&D collaborator with upfront and milestone payments up to $780 million, plus tiered royalties. SEED has achieved 3 milestones with Lilly R&D collaboration.

"I’m delighted to announce SEED’s substantial progress in advancing internal initiatives, including an oncology asset advancing towards first human dose in the first half of 2025, Tau degraders for neurodegeneration advancing towards lead molecule status towards the end of 2024. In addition, we have a synergistic collaboration with Eli Lilly, which achieved multiple milestone payments. In the recent "Nature Biotechnology" review article on molecular glues, it was truly a privilege for SEED Therapeutics to be recognized alongside other prominent companies employing groundbreaking TPD molecular glue strategies. Leveraging our unique and proprietary RITE3 platform that focuses on predicting, detecting, and utilizing a pre-existing weak interaction between an E3 ligase and the target disease-causing protein, SEED consistently garners growing interest for additional partnerships and investment," said Dr. James Tonra, President and CSO of SEED Therapeutics.

An archived replay of the webinar will be available on BeyondSpring’s website www.beyondspringpharma.com under "Events and Presentations" in the Investors section.

Trevor M. Feinstein, M.D.
Dr. Feinstein is board certified in medical oncology and hematology. He joined Piedmont Cancer Institute in 2011 and is the Director of Research at Piedmont Fayette Hospital. Dr. Feinstein is actively involved in clinical trials focused on improved therapies for various cancers. He is a member of Georgia CORE’s research committee along with Georgia Society for Clinical Oncology Clinical Practice Committee. He also chairs the Lung Disease Group for the entire OneOncology network. He is a co-investigator on several peer-reviewed research projects and has authored numerous publications and abstracts in Hematology and Oncology. Dr. Feinstein graduated from the University of Illinois medical school and completed his residence and fellowships at the University of Pittsburgh.

Alberto Chiappori, M.D.

Dr. Chiappori is board certified in medical oncology. He serves as senior member of oncology and medicine for the Thoracic Oncology Program at the H. Lee Moffitt Cancer Center and Research Institute in Tampa and Florida. Dr. Chiappori is an active member of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper), the American Association for Cancer Research (AACR) (Free AACR Whitepaper), and the International Association for the Study of Lung Cancer (IASLC). Dr. Chiappori received his M.D. from the Universidad Peruana Cayetano Heredia in Lima, Peru, completed his residency at Southern Illinois University School of Medicine in Springfield, Illinois, and finished his fellowship and senior fellowship in medical oncology-hematology at Vanderbilt University School of Medicine in Nashville, Tennessee.

Steven Lin, M.D., Ph.D.
Dr. Lin is a Professor and Physician-Scientist at MD Anderson Cancer Center, with joint appointments in the Departments of Radiation Oncology and Experimental Radiation Oncology. Dr. Lin’s practice focuses on thoracic malignancies, and he oversees several clinical trials including the use of proton beam therapy for esophageal cancer and in the combination of immunotherapy with radiotherapy in lung and esophageal cancers. Dr. Lin runs a translational research team that evaluates biomarkers for treatment response and disease outcomes after cancer therapy. Dr. Lin acquired his M.D. and Ph.D. in the Medical Scientist Training Program at the University of California Irvine Medical School. He went on for residency training in Radiation Oncology at The Johns Hopkins Hospital.

On May 16, 2024 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported updated clinical data from a Phase 1b combination cohort evaluating vepdegestrant, an investigational oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in combination with palbociclib (IBRANCE) (Press release, Arvinas, MAY 16, 2024, View Source [SID1234643387]). After six months of additional follow-up, these data are consistent with data presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2023, and show that vepdegestrant plus palbociclib continue to demonstrate encouraging clinical activity in heavily pre-treated patients with a median of four lines of prior therapy with locally advanced or metastatic ER positive (ER+)/human epidermal growth factor 2 (HER2) negative (ER+/HER2-) breast cancer. These updated data were presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer Annual Congress.

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"We’re encouraged by the clinical activity and safety profile observed with vepdegestrant in combination with palbociclib in patients being treated for advanced ER+/HER2- breast cancer," said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. "The median progression-free survival and duration of response data suggest a promising therapeutic benefit for these patients regardless of ESR1 mutation status."

Vepdegestrant is an investigational PROTAC ER degrader designed to harness the body’s natural protein disposal system to specifically target and degrade the estrogen receptor. Vepdegestrant is being co-developed by Arvinas and Pfizer and is being evaluated as a monotherapy in the second-line setting in the ongoing Phase 3 VERITAC-2 trial and in the first-line setting in combination with palbociclib in the ongoing study lead-in cohort of the Phase 3 VERITAC-3 trial.

"Pfizer is focused on advancing the next generation of treatment breakthroughs for people with breast cancer," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "With vepdegestrant, we hope to establish a new standard-of-care endocrine therapy backbone for patients with ER+/HER2- breast cancer, and the data shared at ESMO (Free ESMO Whitepaper) Breast Cancer continue to reinforce its potential."

"This study evaluating vepdegestrant in combination with palbociclib among heavily pre-treated patients with advanced ER+/HER2- metastatic breast cancer is consistent with the clinical activity, safety, and tolerability outcomes reported at SABCS 2023," said Erika Hamilton, M.D., Director Breast Cancer Research and Executive Chair, Breast Cancer Research Executive Committee, Sarah Cannon Research Institute in Nashville, Tennessee, and a lead investigator in the vepdegestrant clinical program and presenting author on the data presentation at ESMO (Free ESMO Whitepaper) Breast Cancer. "The data show promise that vepdegestrant could be a potential addition to current treatment options for this patient population, where there are significant unmet needs."

Vepdegestrant + Palbociclib Phase 1b Study
The Phase 1b cohort of the ARV-471-mBC-101 study (NCT04072952) is designed to assess the safety, tolerability, and anti-tumor activity of vepdegestrant in combination with palbociclib among 46 patients with heavily pre-treated locally advanced or metastatic ER+/HER2- breast cancer. Patients in the study received a median of four prior therapies (median of three in the metastatic setting); 87% were previously treated with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor; 80% were previously treated with fulvestrant; and 78% were previously treated with chemotherapy, including 48% in the metastatic setting.

Patients were treated once daily with oral doses of vepdegestrant at 180 mg (n=2), the recommended Phase 3 dose (RP3D) of 200 mg (n=21), 400 mg (n=3) or 500 mg (n=20), plus 125 mg of palbociclib given orally once daily for 21 days, followed by seven days off treatment in 28-day cycles. Initial data were presented at SABCS 2023 based on a data cutoff of June 6, 2023.

After six months of additional follow-up with a data cutoff of December 18, 2023, updated data from the study continue to demonstrate an encouraging clinical benefit rate, objective response rate and progression-free survival, and a consistent safety profile as previously reported at SABCS 2023.

Data presented at the 2024 ESMO (Free ESMO Whitepaper) Breast Cancer Annual Congress:

Clinical Benefit Rate (CBR):

CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥24 weeks across all dose levels (n = 46) was 63% (95% CI: 47.5 – 76.8), with a CBR of 72% in patients with mutant ESR1 (n=29; 95% CI: 52.8 – 87.3) and a CBR of 53% in patients with wild-type ESR1 (n=15; 95% CI: 26.6 – 78.7).
CBR in patients dosed at the RP3D of 200 mg (n=21) was 67% (95% CI: 43.0 – 85.4) with a CBR of 79% in patients with mutant ESR1 (n=14; 95% CI: 49.2 – 95.3) and a CBR of 43% in patients with wild-type ESR1 (n=7; 95% CI: 9.9 – 81.6)
Objective Response Rate (ORR) and Duration of Response (DOR):

The ORR in evaluable patients with measurable disease at baseline (n=31) was 42% (95% CI: 24.5 – 60.9) with a median DOR in 13 responders of 14.6 months (95% CI: 9.5 – not reached). At the RP3D of 200 mg (n=15), the ORR was 53% (95% CI: 25.6 – 78.7).
ORR in patients with mutant ESR1 (n=17): 47% (95% CI: 23.0 – 72.2).
ORR at the RP3D of 200 mg (n=10): 60% (95% CI: 26.2 – 87.8).
ORR in patients with wild-type ESR1 (n=12): 42% (95% CI: 15.2 – 72.3).
ORR at the RP3D of 200 mg (n=5): 40% (95% CI: 5.3 – 85.3).
Progression-free Survival (PFS):

Median PFS (mPFS) based on 27 (59%) events across all dose levels was 11.2 months (95% CI: 8.2 – 16.5) with a mPFS of 13.7 months (95% CI: 8.2 – NR) in patients with ESR1 mutation (n=29) and mPFS of 11.1 months (95% CI: 2.8 – 19.3) in patients with wild-type ESR1 (n=15).
mPFS in patients dosed at the RP3D of 200 mg (n=21) based on 12 events (57%) was 13.9 months (95% CI: 8.1 – NR) with a mPFS of 13.9 months (95% CI: 8.1 – NR) in patients with ESR1 mutation (n=14) and mPFS of 11.2 months (95% CI: 1.8 – NR) in patients with wild-type ESR1 (n=7).
Circulating Tumor DNA (ctDNA):

Exploratory ctDNA analyses found marked reduction (median change, −98.9%) in tumor fraction after one treatment cycle (all dose groups) regardless of ESR1 mutant status and robust on-treatment decreases in mutant ESR1 ctDNA levels sustained through cycle 7 (evaluated in patients in 200 mg dose cohort), as presented in the poster session.
Safety Profile:

The safety profile of vepdegestrant plus palbociclib was consistent with what was previously reported with Grade 3/4 treatment-related adverse events (TRAEs) ≥10% of neutropenia (91%) and decreased white blood cell count (15%); no grade 5 TRAEs or febrile neutropenia were reported.
The majority of Grade 4 neutropenia events occurred in the first cycle of treatment and occurrences of Grade 3/4 neutropenia decreased following palbociclib dose reductions as described in the prescribing label.
The safety profile of vepdegestrant in combination with palbociclib was otherwise consistent with the profile of palbociclib and what has been observed in other clinical trials for vepdegestrant. Three of 46 patients discontinued palbociclib due to neutropenia including one out of 21 patients treated with the RP3D of vepdegestrant (200 mg) plus palbociclib 125 mg.
About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.

About IBRANCE (palbociclib) 125 mg tablets and capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.2,3 In the U.S., IBRANCE is a prescription medicine indicated for the treatment of adults with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as the first hormonal based therapy; or with fulvestrant in people with disease progression following hormonal therapy.

The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here.

IMPORTANT IBRANCE(palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles 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) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g., hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.