On May 29, 2020 Eisai reported updated results from ENHANCE 1, a Phase 1b/2 study exploring the investigational combination of eribulin plus pembrolizumab in patients with metastatic triple-negative breast cancer (mTNBC) from a poster discussion session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program from May 29-31 (Abstract# 1015 / Poster# 100) (Press release, Eisai, MAY 29, 2020, View Source [SID1234558759]).

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Eisai logo. (PRNewsFoto/Eisai Inc.) (PRNewsfoto/Eisai Inc.)
Eisai logo. (PRNewsFoto/Eisai Inc.) (PRNewsfoto/Eisai Inc.)
This open-label, single-arm, multicenter, Phase 1b/2 study enrolled patients with mTNBC who had previously received zero to two systemic therapies for metastatic disease and were stratified by prior number of therapy (Stratum 1 = 0 prior therapies; Stratum 2 = 1-2 prior therapies). As there were no dose-limiting toxicities observed in Phase 1, patients received the recommended Phase 2 dose of eribulin (1.4 mg/m2 intravenously on Day 1 and Day 8) and pembrolizumab (200 mg intravenously on Day 1) of a 21-day cycle. At the time of data cutoff (July 31, 2019), 167 patients were enrolled (of which 149 patients had confirmed PD-L1 status). The primary objectives were safety and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent imaging review. Secondary objectives included progression free survival (PFS), overall survival (OS), duration of response (DOR) and clinical benefit rate (CBR) overall and by PD-L1 status. Previous findings from ENHANCE 1 were presented during a Spotlight Session at the San Antonio Breast Cancer Symposium (SABCS) in 2017.

Updated findings presented during ASCO (Free ASCO Whitepaper)20 showed:

In the study, no dose-limiting toxicities were observed. Safety information is consistent with previous reports.
Of the total patients enrolled (N=167), the combination of eribulin plus pembrolizumab resulted in an overall ORR of 23.4% (95% CI: 17.2-30.5), the primary efficacy endpoint of the study. The ORR in Stratum 1 (n=66) was 25.8% (95% CI: 15.8-38.0), and the ORR in Stratum 2 (n=101) was 21.8% (95% CI: 14.2-31.1). The overall median PFS was 4.1 months (95% CI: 3.5-4.2 months), and the overall median OS was 16.1 months (95% CI: 13.3-18.5 months), which were secondary endpoints of the study.
In Stratum 1 of patients with confirmed PD-L1 status who received the combination of eribulin plus pembrolizumab in the first line (n=60):
ORR was 34.5% (95% CI: 17.9-54.3) in patients with PD-L1+ tumors (n=29) and 16.1% (95% CI: 5.5-33.7) in patients with PD-L1- tumors (n=31)
The median PFS was 6.1 months (95% CI: 4.1-10.2 months) for patients with PD-L1+ tumors and 3.5 months (95% CI: 2.0-4.2 months) for patients with PD-L1- tumors
The median OS was 21 months (95% CI: 8.3-29.0 months) for patients with PD-L1+ tumors and 15.2 months (95% CI: 12.8-19.4 months) for patients with PD-L1- tumors
The median DOR was 8.3 months (95% CI: 3.2 months-NE) for patients with PD-L1+ tumors and 15.2 months (95% CI: 6.5-22.2 months) for patients with PD-L1- tumors
In Stratum 2 of patients with confirmed PD-L1 status who received the combination of eribulin plus pembrolizumab in the second line or later (n=89):
ORR was 24.4% (95% CI: 12.9-39.5) in patients with PD-L1+ tumors (n=45) and 18.2% (95% CI: 8.2-32.7) in patients with PD-L1- tumors (n=44)
The median PFS was 4.1 months (95% CI: 2.1-4.8 months) for patients with PD-L1+ tumors and 3.9 months (95% CI: 2.3-6.3 months) for patients with PD-L1- tumors
The median OS was 14 months (95% CI: 11.0-19.4 months) in patients with PD-L1+ tumors and 15.5 months (95% CI: 12.4-18.7 months) in patients with PD-L1- tumors
The median DOR was 8.2 months (95% CI: 5.1-25.1 months) for patients with PD-L1+ tumors and 8.6 months (95% CI: 3.5-13.2 months) for patients with PD-L1- tumors
The most common treatment-emergent adverse events were fatigue (66%), nausea (57%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). No deaths were considered treatment related. The most common possibly immune-related TEAEs for pembrolizumab (occurring in >3% of patients) were hypothyroidism (18%), pneumonitis (11%), hyperthyroidism (8%) and infusion-related reaction (3%).

"Treatment options for metastatic triple-negative breast cancer remain limited, despite advances in the field," said Dr. Takashi Owa, Vice President, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. "As a human health care company, we are committed to addressing cancers that remain difficult to treat, and this is evident in our ongoing investigation in triple-negative disease. As long as unmet needs exist, Eisai will persist in our efforts to innovate for patients."

This release discusses an investigational use for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

Previously, data from ENHANCE 1 was reported at the San Antonio Breast Cancer Symposium in 2016 and 2017.

The study is being conducted under an existing clinical trial collaboration agreement between Eisai and Merck.

About HALAVEN (eribulin mesylate) Injection
HALAVEN (eribulin mesylate) injection is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

Discovered and developed by Eisai, eribulin is a synthetic analog of halichondrin B, a natural product that was isolated from the marine sponge Halichondria okadai. First in the halichondrin class, eribulin is a microtubule dynamics inhibitor. Eribulin is believed to work primarily via a tubulin-based mechanism that causes prolonged and irreversible mitotic blockage, ultimately leading to apoptotic cell death. Additionally, in preclinical studies of human breast cancer, eribulin demonstrated complex effects on the tumor biology of surviving cancer cells, including increases in vascular perfusion resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype, promoting the epithelial phenotype, opposing the mesenchymal phenotype. Eribulin has also been shown to decrease the migration and invasiveness of human breast cancer cells.

Important Safety Information

Warnings and Precautions

Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC. Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome.

Adverse Reactions
In patients with mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).

Use in Specific Populations
Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

For more information about HALAVEN, click here for the full Prescribing Information.

HALAVEN is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

On May 29, 2020 Amphivena Therapeutics, a clinical-stage immuno-oncology company focused on developing immunotherapeutics that restore anti-cancer immunity to the patient, reported data from a Phase 1 study of its lead clinical candidate AMV564 in a poster presentation at the ASCO (Free ASCO Whitepaper) Virtual Annual Meeting (Press release, Amphivena Therapeutics, MAY 29, 2020, View Source [SID1234558758]).

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The Phase 1 dose escalation study (NCT04128423) has enrolled 18 advanced solid tumor patients at the time of data cut off. AMV564 was administered once daily via subcutaneous injection, either alone or in combination with pembrolizumab for 2 weeks out of every 3-week cycle.

AMV564 was well tolerated with no dose-limiting toxicities reported in monotherapy or combination therapy cohorts. Assessment of the pharmacodynamic effects of AMV564 using patient blood samples at various timepoints demonstrated depletion of myeloid derived suppressor cells (MDSC) and increases in CD8:Treg ratio with AMV564 treatment.

AMV564 demonstrated single-agent activity including one complete response in a patient with heavily pre-treated (including prior checkpoint inhibitor therapy) ovarian cancer, who remains on study after 10 cycles of treatment. The disease control rates for the monotherapy and combination arms were 45 percent and 29 percent, respectively.

Details of the Presentation:

Title: A Phase 1 Study to Evaluate the T-cell Engager AMV564 Alone and in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors
Authors: Starodub, A. et al.
Abstract Number: 3101 (Poster: 165)

The full abstract and poster will be available on ASCO (Free ASCO Whitepaper) conference and Amphivena websites as of 8:00AM ET on Friday, May 29th.

About AMV564

AMV564 relieves immune suppression via targeted depletion of MDSC and drives T cell activation and polarization to restore anti-cancer immunity. To date, over 80 patients have received AMV564 across three Phase 1 clinical trials for patients with solid tumors, acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS).

On May 29, 2020 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it has completed the secondary offering of 13,014,646 shares of its common stock held by Sanofi, which includes the exercise in full of the underwriters’ option to purchase additional shares from Sanofi, at a public offering price of $515.00 per share (Press release, Regeneron, MAY 29, 2020, View Source [SID1234558757]). The Company also announced the completion of its repurchase of 9,806,805 shares directly from Sanofi at a price of $509.85 per share (representing the price paid by the underwriters in the offering), for an aggregate purchase amount of $5 billion. Pursuant to the offering and repurchase, Sanofi has disposed of all of its shares of common stock in Regeneron, other than 400,000 shares that it is retaining.

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Regeneron did not receive any of the proceeds from the sale of shares of its common stock by Sanofi. The public offering occurred simultaneously in the United States and internationally through underwriters led by BofA Securities and Goldman Sachs & Co. LLC, together with Barclays, BNP Paribas, Citigroup, J.P. Morgan, Morgan Stanley as joint book-running managers.

Regeneron has filed a registration statement (including a prospectus) with the SEC for the offering. Before you invest, you should read the prospectus in that registration statement and other documents Regeneron has filed and will file with the SEC, including the final prospectus supplement dated May 26, 2020, for more complete information about Regeneron and this offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, any underwriter or any dealer participating in the offering will arrange to send you the prospectus and the prospectus supplement, if you request them by contacting BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department or by email at [email protected]; or Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, via telephone: 1-866-471-2526, or via email: [email protected].

On May 29, 2020 Sumitovant Biopharma Ltd. announced that Myovant Sciences (NYSE: MYOV), a healthcare company focused on redefining care for women and for men, and one of five healthcare companies in the Sumitovant family of companies, reported that additional results from its Phase 3 HERO study of once-daily, oral relugolix (120 mg) in men with advanced prostate cancer presented orally at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program and simultaneously published in the New England Journal of Medicine (NEJM) (Press release, Sumitovant Biopharma, MAY 29, 2020, View Source [SID1234558755]). The data expand on earlier findings from the HERO study, demonstrating the superiority of relugolix to leuprolide acetate across multiple endpoints, and further show that treatment with relugolix was associated with a lower risk of major adverse cardiovascular events compared to leuprolide acetate.

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Relugolix met the primary endpoint and demonstrated superiority to leuprolide acetate across six key secondary endpoints, all with p-values < 0.0001. In the primary endpoint responder analysis, 96.7% of men receiving once-daily, oral relugolix achieved sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks, compared to 88.8% of men treated with leuprolide acetate.

Detailed secondary endpoint data, presented and published today, showed notable differences in the rapid and profound suppression of testosterone, PSA response, and testosterone recovery after discontinuation of treatment. In the relugolix group, testosterone suppression to less than 50 ng/dL was achieved in 56.0% of men by Day 4 and 98.7% by Day 15, compared to 0.0% by Day 4 and 12.1% by Day 15 for men in the leuprolide acetate group. Additionally, in the relugolix group, profound testosterone suppression to less than 20 ng/dL was achieved in 78.4% of men at Day 15, compared to 1.0% at Day 15 for men in the leuprolide acetate group. A higher proportion of men in the relugolix group achieved a 50% reduction in PSA by Day 15 and confirmed at Day 29 compared to those in the leuprolide acetate group (79.4% vs. 19.8%, respectively). Within 90 days of treatment discontinuation, 54% of men in the relugolix group achieved normal testosterone levels (≥ 280 ng/dL) with a mean testosterone level of 288.4 ng/dL, compared to 3% of men in the leuprolide acetate group with a mean testosterone level of 58.6 ng/dL.

"A faster effect in lowering testosterone for prostate cancer patients can be clinically significant – likewise, a more rapid testosterone recovery after stopping treatment, could potentially improve a patient’s quality of life," said Neal Shore, M.D., medical director of the Carolina Urologic Research Center, HERO program steering committee member, presenter of the ASCO (Free ASCO Whitepaper) data, and lead author on the NEJM paper. "Both of these findings could make a meaningful difference in the treatment journey for men with advanced prostate cancer."

Men in the relugolix group had a 54% lower risk of major adverse cardiovascular events compared to men in the leuprolide acetate group (2.9% vs. 6.2%, respectively). Additionally, in men with a history of these events, the relugolix group had 80% fewer major adverse cardiovascular events reported compared to the leuprolide acetate group (3.6% vs. 17.8%, respectively). More than 90% of men in the HERO study had at least one cardiovascular risk factor, including lifestyle risk factors such as tobacco use and obesity, comorbidities such as diabetes and hypertension, and prior history of a major adverse cardiovascular event.

"Cardiovascular disease is the leading cause of death in men with prostate cancer," said Dr. Shore. "An oral therapeutic option with strong efficacy that also reduces cardiovascular risk compared to that of conventional GnRH agonist therapy would be a critical achievement for men with advanced prostate cancer."

As previously reported, the incidence of adverse events in the HERO study was comparable for relugolix and leuprolide acetate groups (92.9% vs. 93.5%, respectively). The most frequently reported adverse events, reported in at least 10% of men in the relugolix group, were hot flashes, fatigue, constipation, mild to moderate diarrhea, and arthralgia.

"Relugolix has the potential to be an important new treatment option for men with prostate cancer and would represent significant progress in our company’s commitment to redefine care for men," said Lynn Seely, M.D., chief executive officer of Myovant Sciences. "We are grateful to have the opportunity to share these additional data through presentation and publication in such highly-respected venues as the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the New England Journal of Medicine. We have already submitted our New Drug Application to the FDA with the goal of bringing this oral, once-daily potential treatment to men with prostate cancer as expeditiously as possible, especially given the current environment with the COVID-19 pandemic and the difficulties and risks men face traveling to hospitals and clinics to receive injections."

Myovant submitted a New Drug Application (NDA) to the FDA for relugolix in April 2020, which, if approved, would be the first and only oral gonadotropin-releasing hormone (GnRH) receptor antagonist treatment for men with advanced prostate cancer.

The ASCO (Free ASCO Whitepaper) presentation (#5602), "HERO phase III trial: Results comparing relugolix, an oral GnRH receptor antagonist, versus leuprolide acetate for advanced prostate cancer," is available for on-demand viewing.

Conference Call
Myovant will hold a conference call to discuss these data on Monday, June 1, 2020 at 8:30 a.m. Eastern Time / 5:30 a.m. Pacific Time. Myovant management will be joined by Neal Shore, M.D. To participate in the live conference call, please dial 1-800-532-3746 for domestic callers and +1-470-495-9166 for international callers. A live webcast of the conference call will also be available on the investor relations page of Myovant’s website at investors.myovant.com and will remain archived on Myovant’s website for at least 30 days.

About the Phase 3 HERO Program in Advanced Prostate Cancer
Myovant’s Phase 3 clinical program for advanced prostate cancer consisted of a randomized, open-label, parallel-group, multinational clinical study designed to evaluate the safety and efficacy of relugolix in men with androgen-sensitive advanced prostate cancer who required at least one year of continuous androgen deprivation therapy. Men enrolled in the study were randomized 2:1 to receive a single loading dose of relugolix 360 mg followed by relugolix 120 mg once daily, or to treatment with leuprolide acetate 3-month depot injection, respectively.

Data from an additional key secondary endpoint, castration resistance-free survival, are expected in the third quarter of 2020.

About Prostate Cancer
Prostate cancer is the second most prevalent form of cancer in men and the second leading cause of death due to cancer in men in the U.S. Cardiovascular mortality is the leading cause of death in men with prostate cancer and accounts for 34% of deaths in men with prostate cancer in the U.S. Approximately three million men in the U.S. are currently living with prostate cancer, and approximately 170,000 men are estimated to be newly diagnosed in 2019. Advanced prostate cancer is prostate cancer that has spread or come back after treatment and may include men with biochemical recurrence (rising PSA in the absence of metastatic disease on imaging), locally advanced disease, or metastatic disease. Treatment for advanced prostate cancer typically involves androgen deprivation therapy, which reduces testosterone to very low levels, commonly referred to as castrate levels. GnRH receptor agonists, such as leuprolide acetate, or slow-release injections are the current standard of care for androgen deprivation therapy. However, GnRH receptor agonists may be associated with mechanism-of-action limitations, including the potentially detrimental initial rise in testosterone levels that can exacerbate clinical symptoms, which is known as clinical or hormonal flare, and delayed testosterone recovery after the drug is discontinued. Approximately 200,000 men are treated with androgen deprivation therapy with a GnRH agonist or antagonist each year.

About Relugolix
Relugolix is a once-daily, oral gonadotropin-releasing hormone (GnRH) receptor antagonist that reduces testicular testosterone production, a hormone known to stimulate the growth of prostate cancer, and ovarian estradiol production, a hormone known to stimulate the growth of uterine fibroids and endometriosis. Myovant is developing relugolix as a monotherapy tablet (120 mg once daily) for men with advanced prostate cancer. Myovant is also developing a relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) for women with uterine fibroids and for women with endometriosis.

On May 29, 2020 The Austrian Breast & Colorectal Cancer Study Group and the Alliance Foundation Trials, LLC, Pfizer Inc. (NYSE: PFE) reported that following a preplanned efficacy and futility analysis, the independent Data Monitoring Committee (DMC) of the collaborative Phase 3 early breast cancer PALbociclib CoLlaborative Adjuvant Study (PALLAS) determined that the trial is unlikely to show a statistically significant improvement in the primary endpoint of invasive disease-free survival (iDFS) (Press release, Pfizer, MAY 29, 2020, View Source [SID1234558748]). Patients currently receiving palbociclib in the study will be advised about next steps by their physicians and long-term follow up of all patients will proceed as planned. No unexpected new safety signals were observed in patients receiving palbociclib.

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The PALLAS trial compares palbociclib plus standard adjuvant endocrine therapy to standard adjuvant endocrine therapy alone in women and men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early (stage 2 and 3) breast cancer and is an academically-led global collaboration, involving more than 400 centers in 21 countries around the globe.

"We are disappointed in this outcome. Breast cancer is a leading cause of death around the world and delaying or preventing the development of metastatic disease is a significant unmet need. PALLAS is a large study with many subgroups and we are actively collaborating to determine if there are patients who may benefit from adjuvant treatment with the palbociclib combination," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "Since its initial approval in 2015, IBRANCE has helped change the treatment landscape for people with HR+, HER2- metastatic breast cancer. We are grateful to all patients, health care providers and our academic partners who have devoted so much to make this important study possible."

"This result is not what we hoped for, but we are steadfast in our commitment to advancing the science and care for people living with breast cancer," said Albert Bourla, Pfizer Chairman and CEO. "Given the continued breadth of our marketed portfolio and strength of our pipeline, our growth projections are not reliant upon any individual marketed medicine or pipeline opportunity. Consequently, we remain highly confident in our ability to deliver, following the closing of the proposed combination of Upjohn with Mylan N.V., a compound annual growth rate for revenues of at least 6% through 2025."

Health authorities and trial investigators have been notified of this decision. When available, the full results from the PALLAS study will be shared with the scientific community at a later date.

Palbociclib is also being studied in patients with high-risk early breast cancer and results from the collaborative PENELOPE-B trial are expected later this year.

In the U.S., IBRANCE is approved for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy. IBRANCE is not indicated in early breast cancer. The collaborative Phase 3 PENELOPE-B study (NCT01864746) continues to explore the potential of IBRANCE in patients with early breast cancer at high risk of recurrence who have residual disease after neoadjuvant chemotherapy.

About the PALLAS Trial

PALLAS is a randomized (1:1), prospective, international, multicenter, open-label Phase 3 study comparing the combination of palbociclib and standard adjuvant endocrine therapy for two years followed by continuing standard adjuvant therapy to complete five years versus at least five years of standard adjuvant endocrine therapy for pre- and postmenopausal women or men with HR+, HER2- early invasive (Stage 2 and Stage 3) breast cancer, including those at moderate to high risk of recurrence. The trial is co-sponsored by the Austrian Breast & Colorectal Cancer Study Group and the Alliance Foundation Trials as part of a clinical research collaboration with Pfizer and other study groups, including PrECOG, LLC; NSABP Foundation Inc; and the Breast International Group (BIG).

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 indicated for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

IBRANCE currently is approved in more than 95 countries and has been prescribed to more than 300,000 patients globally.

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.

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At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of patients. Today, Pfizer Oncology has an industry-leading portfolio of 22 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, prostate, kidney and lung cancers, as well as leukemia and melanoma.