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.

About Pfizer Oncology

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.

On May 29, 2020 Varian (NYSE: VAR) reported that Dow Wilson, Chief Executive Officer, J. Michael Bruff, Chief Financial Officer, and Anshul Maheshwari, Vice President, Investor Relations and Treasurer will participate in a virtual fireside chat at the Goldman Sachs Global Virtual Healthcare Conference, scheduled for 11:20 a.m. Eastern Time on Tuesday, June 9, 2020 (Press release, Varian Medical Systems, MAY 29, 2020, View Source [SID1234558747]).

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Information about the webcast of the company’s presentation will be available through a link on the company website at www.varian.com/investors.

On May 29, 2020 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has approved Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) for the treatment of people with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, Genentech, MAY 29, 2020, View Source [SID1234558746]).

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"We’re excited that today’s approval of Tecentriq in combination with Avastin for unresectable or metastatic hepatocellular carcinoma brings a cancer immunotherapy option to people with this aggressive form of liver cancer," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "The application was reviewed under the FDA’s Real-Time Oncology Review pilot and Project Orbis initiative, helping to bring this new treatment option rapidly to patients in the United States and around the world."

"The results of the IMbrave150 study are really transformative for patients with advanced liver cancer, one of the few cancers with a rising death rate and limited options in the first-line setting," said Dr. Richard Finn, Professor of Medicine at the David Geffen School of Medicine at UCLA and Director of the Signal Transduction and Therapeutics Program at the UCLA Jonsson Comprehensive Cancer Center. "For the first-time we have a regimen that markedly improves survival over sorafenib, the standard of care for first-line hepatocellular carcinoma since 2007, and offers patients the opportunity for improved disease control with a favorable tolerability profile."

The review of this application was conducted under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners. According to the FDA, collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions. Simultaneous applications were submitted to regulators in the United States, Australia, Canada and Singapore under Project Orbis. Additionally, the FDA rapidly reviewed and approved the application under its Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

The approval was based on results from the Phase III IMbrave150 study, which demonstrated that Tecentriq in combination with Avastin reduced the risk of death (overall survival; OS) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42-0.79; p=0.0006) and reduced the risk of disease worsening or death (progression-free survival; PFS) by 41% (HR=0.59; 95% CI: 0.47-0.76; p<0.0001), compared with sorafenib. IMbrave150 is the first Phase III cancer immunotherapy study to show an improvement in OS and PFS in people with unresectable or metastatic HCC compared with sorafenib. Serious adverse reactions (Grade 3-4) occurred in 38% of people in the Tecentriq and Avastin arm. The most frequent serious adverse reactions (≥2%) were bleeding in the gastrointestinal tract, infections and fever. These results were published in the New England Journal of Medicine on May 14, 2020.

Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across several types of lung, genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

For those who qualify, Genentech offers patient assistance programs for people taking Tecentriq through Genentech Access Solutions. Doctors can contact Genentech Access Solutions at (866) 422-2377. More information is also available at View Source

About the IMbrave150 study

IMbrave150 is a global Phase III, multicenter, open-label study of 501 people with unresectable or metastatic HCC who had not received prior systemic therapy. People were randomized 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq was administered intravenously (IV), 1200 mg on day 1 of each 21-day cycle, and Avastin was administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle. People received the combination or the control arm treatment until disease progression or unacceptable toxicity. The two primary endpoints were OS and independent review facility (IRF)-assessed PFS per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Additional study endpoints were IRF-assessed overall response rate (ORR) per RECIST and mRECIST.

About hepatocellular carcinoma

According to the American Cancer Society, it is estimated that more than 42,000 Americans will be diagnosed with liver cancer in 2020. Liver cancer incidence has more than tripled since 1980. HCC accounts for approximately 75% of all liver cancer cases in the United States. HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B and C) or alcohol consumption, and typically presents at an advanced stage where there are limited treatment options.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

About Avastin (bevacizumab)

Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize).

Tecentriq U.S. Indication

Tecentriq is a prescription medicine used to treat adults with:

A type of liver cancer called hepatocellular carcinoma (HCC).

Tecentriq may be used with the medicine bevacizumab when their liver cancer:
has spread or cannot be removed by surgery, and
they have not received other medicines by mouth or injection through their vein (IV) to treat their cancer.
It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Lung problems (pneumonitis)–signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucus in stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary)–signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of the face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with Tecentriq
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used in hepatocellular carcinoma with bevacizumab include:

high blood pressure
feeling tired or weak
too much protein in the urine
Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please see View Source for full Prescribing Information and additional Important Safety Information.

Avastin is approved for:

Avastin, in combination with atezolizumab, is indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Possible serious side effects

Everyone reacts differently to Avastin therapy. So, it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not. Their doctor will stop treatment if any serious side effects occur. Patients should contact their health care team if there are any signs of these side effects.

GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
Abnormal passage in the body. This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
Wounds that don’t heal. A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgical wounds are fully healed
Serious bleeding. This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If a patient has recently coughed up blood or had serious bleeding, they should be sure to tell their doctor
Severe high blood pressure. Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
Kidney problems. These may be caused by too much protein in the urine and can sometimes be fatal
Infusion-related reactions. These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. The patient’s doctor or nurse will monitor for signs of infusion reactions
Severe stroke or heart problems. These may include blood clots, mini-stroke, heart attack, chest pain, and the heart may become too weak to pump blood to other parts of the body (congestive heart failure). These can sometimes be fatal
Nervous system and vision problems. Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness
Side effects seen most often

In clinical studies across different types of cancer, some patients experienced the following side effects:

High blood pressure
Too much protein in the urine
Nosebleeds
Rectal bleeding
Back pain
Headache
Taste change
Dry skin
Inflammation of the skin
Inflammation of the nose
Watery eyes
Avastin is not for everyone

Patients should talk to their doctor if they are:

Undergoing surgery. Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
Pregnant or think they are pregnant. Data have shown that Avastin may harm a woman’s unborn baby. Birth control should be used while patients are on Avastin. If Avastin is stopped, patients should keep using birth control for 6 months before trying to become pregnant
Planning to become pregnant. Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children
Breastfeeding. Breastfeeding while on Avastin may harm the baby, therefore women should not breastfeed during and for 6 months after taking Avastin
Patients should talk with their doctor if they have any questions about their condition or treatment.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

For full Prescribing Information and Boxed WARNINGS on Avastin please visit View Source

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentech’s approved PD-L1 checkpoint inhibitor, the company’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. For more information visit View Source

On May 29, 2020 Eisai (CEO: Haruo Naito) and Merck & Co., Inc., Kenilworth, N.J., U.S.A. known as MSD outside the United States and Canada, reported that results from two trials evaluating LENVIMA, an orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A., will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO20 Virtual Scientific Program) from May 29 to 31, 2020 (Press release, Eisai, MAY 29, 2020, View Source [SID1234558745]). The two trials, Study 116/KEYNOTE-524 and Study 111/KEYNOTE-146, examined patients with unresectable hepatocellular carcinoma (HCC) with no prior systemic therapy and patients with metastatic clear cell renal cell carcinoma (ccRCC) who progressed following immune checkpoint inhibitor therapy, respectively.

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"The tumor response rates demonstrated with KEYTRUDA plus LENVIMA in these studies underscore the potential of this combination regimen in certain types of hepatocellular and renal cell carcinoma," said Dr. Jonathan Cheng, Vice President, Oncology Clinical Research, Merck & Co., Inc., Kenilworth, N.J., U.S.A. Research Laboratories. "KEYTRUDA plus LENVIMA is an important pillar of our broad oncology research program, and we continue to advance the study of the combination across multiple types of cancers and stages of disease."

"As data from our combination trials continue to read out, our enthusiasm for and belief in the potential of LENVIMA plus KEYTRUDA are strengthened by the growing body of evidence observed in multiple advanced cancers," said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. "Our ongoing clinical study efforts on this combination exemplify our commitment to following the science and exploring possible solutions for patients affected by difficult-to-treat cancers."

Results from Study 116/KEYNOTE-524 (Abstract #4519) are being presented in a poster discussion session, and results from Study 111/KEYNOTE-146 (Abstract #5008) are being presented in an oral abstract session of the virtual scientific program of the 2020 ASCO (Free ASCO Whitepaper) Annual Meeting.

Study 116/KEYNOTE-524 Trial Design and Data (Abstract #4519)

Study 116/KEYNOTE-524 (ClinicalTrials.gov, NCT03006926(New Window)) is a Phase 1b, open-label, single-arm trial evaluating the LENVIMA plus KEYTRUDA combination in 100 patients with unresectable HCC with no prior systemic therapy. Patients were treated with LENVIMA 8 or 12 mg (based on baseline body weight ˂60 kilograms or ≥60 kilograms, respectively) orally once daily in combination with KEYTRUDA 200 mg intravenously every three weeks. The primary endpoints are ORR and duration of response (DOR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1 per independent imaging review (IIR). Secondary endpoints include progression-free survival (PFS), time to progression (TTP) and overall survival (OS). At data cutoff (October 31, 2019) and a median duration of follow-up of 10.6 months (95% CI: 9.2-11.5), 37 patients were still on study treatment (LENVIMA plus KEYTRUDA: n=34; LENVIMA only: n=3), and median duration of treatment exposure to the LENVIMA plus KEYTRUDA combination was 7.9 months (range: 0.2-31.1).

The final analysis of the study’s primary endpoints showed the LENVIMA plus KEYTRUDA combination demonstrated an ORR of 36% (n=36) (95% CI: 26.6-46.2), with a complete response rate of 1% (n=1) and a partial response rate of 35% (n=35), and a median DOR of 12.6 months (95% CI: 6.9-not estimable [NE]), using RECIST v1.1 criteria per IIR. As assessed using mRECIST criteria per IIR, the LENVIMA plus KEYTRUDA combination demonstrated an ORR of 46% (n=46) (95% CI: 36.0-56.3), with a complete response rate of 11% (n=11) and a partial response rate of 35% (n=35), and a median DOR of 8.6 months (95% CI: 6.9-NE).

Treatment-related adverse events (TRAEs) led to discontinuation of LENVIMA and KEYTRUDA in 6% of patients, of LENVIMA in 14% of patients, and of KEYTRUDA in 10% of patients. Grade ≥3 TRAEs occurred in 67% of patients (Grade 3: 63%; Grade 4: 1%; Grade 5: 3%). There was one Grade 4 TRAE (leukopenia/neutropenia), and there were three treatment-related deaths (acute respiratory failure/acute respiratory distress syndrome, intestinal perforation and abnormal hepatic function; n=1 for each). The most common TRAEs of any grade (≥20%) were hypertension (36%), diarrhea (35%), fatigue (30%), decreased appetite (28%), hypothyroidism (25%), palmar-plantar erythrodysesthesia syndrome (23%), decreased weight (22%), dysphonia (21%), increased aspartate aminotransferase (20%) and proteinuria (20%).

Study 111/KEYNOTE-146 Trial Design and Data from the RCC Cohort (Abstract #5008)

KEYNOTE-146/Study 111 (ClinicalTrials.gov, NCT02501096(New Window)) is a Phase 1b/2, open-label, single-arm trial evaluating the LENVIMA plus KEYTRUDA combination in patients with selected solid tumors. Results from the RCC cohort of the Phase 2 part of the study are based on 104 patients with metastatic ccRCC with disease progression following PD-1/PD-L1 immune checkpoint inhibitor therapy using RECIST v1.1 criteria. Patients were treated with LENVIMA 20 mg orally once daily in combination with KEYTRUDA 200 mg intravenously every three weeks until unacceptable toxicity or disease progression. The primary endpoint is ORR at week 24 by immune-related RECIST (irRECIST) per investigator review. The key secondary endpoints include ORR, PFS, OS, safety and tolerability for a maximum of 35 cycles/treatments (approximately two years).

At data cutoff (April 9, 2020), results from the Phase 2 part of the study showed the LENVIMA plus KEYTRUDA combination demonstrated an ORR at week 24 of 51% (95% CI: 41-61) by irRECIST per investigator review. As assessed by irRECIST per investigator review, ORR was 55% (95% CI: 45-65), with a partial response rate of 55%, stable disease rate of 36% and progressive disease rate of 5% (5% were not evaluable). Median DOR was 12 months (95% CI: 9-18). Median PFS was 11.7 months (95% CI: 9.4-17.7), and the 12-month PFS rate was 45% (95% CI: 32-57). Median OS was not reached (95% CI:16.7-NR), and the 12-month OS rate was 77% (95% CI: 67-85).

As assessed by RECIST v1.1 per investigator review, ORR was 52% (95% CI: 42-62), with a partial response rate of 52%, stable disease rate of 38% and progressive disease rate of 6% (5% were not evaluable). Median DOR was 12 months (95% CI: 9-18). Median PFS was 11.3 months (95% CI: 7.6-17.7), and the 12-month PFS rate was 44% (95% CI: 31-55).

Treatment-related adverse events (TRAEs) led to discontinuation of LENVIMA and KEYTRUDA in 15% of patients, discontinuation of LENVIMA in 12% of patients, and discontinuation of KEYTRUDA in 12% of patients (2% due to proteinuria). Grade 4 TRAEs included lipase increased, diverticulitis, large intestine perforation and myocardial infarction, and Grade 5 TRAEs included upper gastrointestinal hemorrhage and sudden death. The most common TRAEs of any grade (≥20%) were fatigue (53%), diarrhea (46%), proteinuria (39%), dysphonia (35%), hypertension (34%), nausea (32%), stomatitis (32%), arthralgia (29%), decreased appetite (28%), palmar-plantar erythrodysesthesia syndrome (25%), hypothyroidism (23%) and headache (22%).

This release discusses investigational uses 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.

LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone. Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 60 countries including Japan, the United States, in Europe and Asia, and for unresectable hepatocellular carcinoma in over 55 countries including Japan, the United States, in Europe, China and in Asia. Additionally, LENVIMA is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 55 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. In addition, LENVIMA is approved in combination with KEYTRUDA (pembrolizumab) as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation in countries including the United States, Australia, and Canada. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

About KEYTRUDA (pembrolizumab) Injection

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck & Co., Inc., Kenilworth, N.J., U.S.A has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

About the Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A. Strategic Collaboration

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s anti-PD-1 therapy KEYTRUDA.

In addition to ongoing clinical studies evaluating the LENVIMA plus KEYTRUDA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in 13 different tumor types (endometrial carcinoma, hepatocellular carcinoma, melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, urothelial cancer, biliary tract cancer, colorectal cancer, gastric cancer, glioblastoma, ovarian cancer and triple-negative breast cancer) across 18 clinical trials.

Eisai’s Focus on Cancer

Eisai focuses on the development of anticancer drugs, targeting the tumor microenvironment (with experience and knowledge from Halaven (Eribulin mesilate) and Lenvima) and the driver gene mutation and aberrant splicing (leveraging RNA Splicing Platform) as areas (Ricchi) where real patient needs are still unmet, and where Eisai can become a frontrunner in oncology. Eisai will discover innovative new drugs with new targets and mechanisms of action from these Ricchi, with the aim of contributing to the cure of cancers.