On June 11, 2020 Pfizer Inc. (NYSE: PFE) reported the United States (U.S.) Food and Drug Administration (FDA) has approved NYVEPRIA (pegfilgrastim-apgf), a biosimilar to Neulasta (pegfilgrastim).1 NYVEPRIA is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia (Press release, Pfizer, JUN 11, 2020, View Source [SID1234561012]).2

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"The FDA approval of NYVEPRIA is a positive step that could both enable cost savings and increase access to an important treatment option," said Andy Schmeltz, Global President, Pfizer Oncology. "We are proud to add this new, long-acting supportive care option to our robust portfolio, now with six FDA-approved oncology biosimilars including three specifically approved for supportive care for patients with cancer. We look forward to making NYVEPRIA available to U.S. patients and physicians later this year."

The FDA approval was based on the review of a comprehensive data package and totality of evidence demonstrating a high degree of similarity of NYVEPRIA to its reference product.

"Chemotherapy-induced febrile neutropenia is a relatively common and severe side effect of some cancer treatments that could cause significant complications and can result in the alteration of treatment regimens," said Ali McBride, PharmD, MS, BCPS, BCOP, Immediate Past President of the Association of Community Cancer Centers (ACCC). "The FDA approval of NYVEPRIA provides clinicians with an additional long-acting treatment option that can help prevent infections in patients undergoing myelosuppressive chemotherapy."

Biosimilars play an important role in the treatment of cancer or as supportive care, with the ability to both help increase patient access to essential medicines and provide value to the healthcare system by driving market competition that can lower the cost of care. With more than a decade of global in-market experience, a portfolio of nine approved biosimilar products in the U.S. and the broadest biosimilar portfolio for oncology supportive care, Pfizer is proud to be a global leader in biosimilars and at the forefront of this vital healthcare segment. Pfizer has also filed its pegfilgrastim biosimilar candidate for regulatory approval with the European Medicines Agency (EMA) and the application is currently under review.

Pfizer is committed to ensuring that patients who are prescribed NYVEPRIA have access to this therapy. Upon launch, patients in the U.S. will have access to Pfizer Oncology Together, which offers personalized support and financial assistance resources to help patients access their prescribed Pfizer Oncology medications. Pfizer Oncology Together can help patients understand their benefits and connect them with financial assistance resources, regardless of their insurance coverage.

About NYVEPRIA (pegfilgrastim-apgf)

NYVEPRIA, a biosimilar to Neulasta, is approved by the FDA to help reduce the chance of infection due to a low white blood cell count in people with non-myeloid cancer who receive anti-cancer medicines, like chemotherapy, that can cause fever and low white blood cell count.2 This condition, known as febrile neutropenia, is a common side effect of many types of chemotherapy and lowers the body’s ability to defend itself against infections.3

NYVEPRIA INDICATION AND IMPORTANT SAFETY INFORMATION

Indication

NYVEPRIA is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Limitations of Use

NYVEPRIA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Important Safety Information

Contraindication

NYVEPRIA is contraindicated in patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products
Reactions have included anaphylaxis
Splenic Rupture

Splenic rupture, including fatal cases, can occur following the administration of pegfilgrastim products
Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving NYVEPRIA
Acute Respiratory Distress Syndrome (ARDS)

Can occur in patients receiving pegfilgrastim products
Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving NYVEPRIA
Discontinue NYVEPRIA in patients with ARDS
Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, can occur in patients receiving pegfilgrastim products
The majority of reported events occurred upon initial exposure
Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti‐allergic treatment
Permanently discontinue NYVEPRIA in patients with serious allergic reactions
Do not administer NYVEPRIA to patients with history of serious allergic reactions to pegfilgrastim products or filgrastim products
Use in Patients with Sickle Cell Disorders

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving pegfilgrastim products
Discontinue NYVEPRIA if sickle cell crisis occurs
Glomerulonephritis

Glomerulonephritis has occurred in patients receiving pegfilgrastim products
The diagnoses were based on azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy
Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation of pegfilgrastim products
If suspected, evaluate for cause, and if causality is likely consider dose-reduction or interruption of NYVEPRIA
Leukocytosis

White blood cell counts of 100 x 109/L or higher have been observed in patients receiving pegfilgrastim products
Monitoring of complete blood count (CBC) during NYVEPRIA therapy is recommended
Capillary Leak Syndrome (CLS)

CLS has been reported after granulocyte-colony stimulating factor (G‐CSF) administration, including pegfilgrastim products
Characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration
Episodes vary in frequency and severity and may be life‐threatening if treatment is delayed
Patients with symptoms should be closely monitored and receive standard symptomatic treatment, which may include intensive care
Potential for Tumor Growth Stimulatory Effects on Malignant Cells

G-CSF receptor, through which pegfilgrastim and filgrastim products act, has been found on tumor cell lines
The possibility that pegfilgrastim products act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded
Aortitis

Aortitis has been reported in patients receiving pegfilgrastim products. It may occur as early as the first week after start of therapy
Manifestations may include generalized signs and symptoms, such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c‑reactive protein and white blood cell count)
Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue NYVEPRIA if aortitis is suspected
Nuclear Imaging

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone imaging results
Most Common Adverse Reactions

Bone pain

On June 11, 2020 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, reported that Brian M. Culley, Chief Executive Officer, will be presenting at the 2020 Raymond James Human Health Innovation Conference on June 18, 2020 at 9:40 am Eastern Time (Press release, Lineage Cell Therapeutics, JUN 11, 2020, View Source [SID1234561011]). Interested investors can access the live presentation on the Events and Presentations section of Lineage’s website.

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The archived presentation will be posted on the Events and Presentations section of Lineage’s website the day following the event and will be available for 30 days. Additional videos are available on the Media page of the Lineage website, located at www.lineagecell.com/media/.

On June 11, 2020 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that it has entered into an agreement to divest a portfolio of select non-core over-the-counter (OTC) and prescription pharmaceutical products sold exclusively in Asia Pacific to Celltrion Inc. ("Celltrion"), an Incheon, South Korea-based biopharmaceutical company specializing in the research, development and manufacturing of small molecules, biosimilars and innovative drugs (Press release, Takeda, JUN 11, 2020, View Source [SID1234561010]). Takeda will receive $266 million USD upfront in cash and up to an additional $12 million USD in potential milestone payments, subject to customary legal and regulatory closing conditions.

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The portfolio to be divested to Celltrion includes a variety of OTC products and pharmaceutical products in the Cardiovascular, Diabetes and General Medicine therapeutic areas sold predominantly in Australia, Hong Kong, Macau, Malaysia, Philippines, Singapore, South Korea, Taiwan and Thailand, which are part of Takeda’s Growth & Emerging Markets Business Unit. The portfolio generated FY 2018 net sales of approximately $140 million USD, driven by strong sales of prescription products Nesina and Edarbi. While the products included in the sale continue to play important roles in meeting patient needs in these countries, they are outside of Takeda’s chosen business areas – Gastroenterology (GI), Rare Diseases, Plasma-Derived Therapies, Oncology and Neuroscience – that are core to its global long-term growth strategy.

"Across our Growth & Emerging Markets, Takeda must focus on accelerating the commercial availability of our highly innovative medicines for patients living with complex and rare conditions, and expanding our approach to Access to Medicines across the Region," said Ricardo Marek, President, Growth & Emerging Markets Business Unit, Takeda. "Doing so, better addresses patient unmet needs. While we remain committed to Asia Pacific, and the Emerging Markets, divesting non-core products helps achieve those goals."

"This announcement marks continued progress on our commitment to divest non-core products as we remain focused on maintaining our financial discipline and rapid deleveraging following our acquisition of Shire," said Costa Saroukos, Chief Financial Officer, Takeda. "One of several transactions since the launch of the divestment program, the sale announced today will further focus Takeda on our five key business areas and our pipeline of innovative medicines. We look forward to continuing to execute and deliver on Takeda’s financial commitments, including paying down debt and focusing our portfolio."

Takeda has made strong progress on its ongoing divestiture program. In March 2020, Takeda completed sales of non-core assets spanning the Russia-CIS region to STADA for $660 million USD and in countries spanning the Near East, Middle East and Africa region to Acino for $200 million USD. In July 2019, Takeda completed the divestiture of Xiidra to Novartis for up to $5.3 billion USD. Additionally, earlier this year, Takeda announced the sales of non-core products in Latin America to Hypera Pharma for $825 million USD and in Europe to Orifarm Group for up to approximately $670 million USD, including the sale of two manufacturing sites in Denmark and Poland.

Takeda intends to use the proceeds from its divestitures to continue to reduce its debt and accelerate deleveraging toward its target of 2x net debt/adjusted EBITDA within March 2022 – March 2024.

Transaction Details

Takeda has entered into an agreement to sell a portfolio of 18 select OTC and prescription pharmaceutical assets sold in Australia, Hong Kong, Macau, Malaysia, Philippines, Singapore, South Korea, Taiwan and Thailand to Celltrion for a total value of up to $278 million USD. Takeda will receive $266 million USD upfront in cash and up to an additional $12 million USD in potential milestone payments, subject to customary legal and regulatory closing conditions.

Takeda and Celltrion have also entered into a manufacturing and supply agreement under which Takeda will continue to manufacture the portfolio of divested products and supply them to Celltrion. Under the terms of the agreement, Celltrion will acquire the rights, title and interest to the products in the portfolio exclusive to these countries.

The transaction is expected to close by end of the calendar year, subject to the satisfaction of customary closing conditions, receipt of required regulatory clearances and, where applicable, compliance with local works council requirements. Until then, Takeda remains the owner of these products and responsible for ensuring patient access to them.

Takeda is being advised by BofA Securities as its financial advisor and White & Case is its legal advisor in this transaction.

On June 11, 2020 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported an update on its clinical pipeline and financial results for the second quarter ended April 30, 2020 (Press release, Advaxis, JUN 11, 2020, View Source [SID1234561009]).

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Key recent corporate and clinical pipeline updates:

Presented updated clinical and preliminary biomarker data from the ongoing Phase 1/2 trial of ADXS-503 in non-small cell lung cancer (NSCLC) demonstrating clinical benefit in two patients with immediate prior progression on KEYTRUDA including one durable response out to 25 weeks and another sustained response out to out least 16 weeks with both patients remaining on treatment in Part B, the combination arm with KEYTRUDA
One sustained partial response with 60% reduction in site lesions at 16 weeks and one durable response of stable disease with 25% reduction in target lesion at 25 weeks confirmed by radiographic scans
Clinical benefit achieved after immediate prior progression on KEYTRUDA with previous best responses of stable disease suggest ADXS-503 may re-sensitize or enhance response to KEYTRUDA
Part A monotherapy has been completed with three of six evaluable patients achieving responses of stable disease
As monotherapy, as well as in combination with KEYTRUDA, ADXS-503 appeared safe and well tolerated with no dose-limiting toxicities
Preliminary biomarker data from seven patients in Part A monotherapy demonstrated activation of cytotoxic and memory CD8+ and CD4+ T cells in 100% of patients and antigen spreading in five of seven evaluable patients, including the first patient in combination therapy
Presented updated survival data from the Phase 1/2 trial with ADXS-PSA in combination with KEYTRUDA at the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium. Data highlights include reported median overall survival (95% CI) of 16.4 months (4.0-NR) (n=11) for advanced prostate cancer patients with prior docetaxel therapy and visceral metastases treated with ADXS-PSA in combination with KEYTRUDA compared to an estimated 11 months with current standard of care. In addition, median overall survival (95% CI) was 33.7 months (15.4-33.7) in all patients treated with ADXS-PSA in combination with KEYTRUDA (n=37)
Announced a research agreement with Personalis to deploy ImmunoID NeXT Platform in the ADXS-503 clinical program. Personalis will conduct comprehensive tumor genomic profiling to enable the identification of predictive composite biomarkers and/or signatures of response, as well as the broad evaluation of potential mechanisms of therapy resistance
Management Commentary
"We have continued our momentum throughout the second quarter with updated clinical data which support the prioritization of our off-the-shelf neoantigen HOT program," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "These updated data from our ongoing Phase 1/2 study of ADXS-503 in NSCLC increase our confidence that ADXS-503 may synergistically enhance and/or restore sensitivity to checkpoint inhibitors and we are particularly encouraged by the sustained clinical benefit observed, now out to 16 and 25 weeks, in two patients who had immediate prior progression on KEYTRUDA. Our results are further supported by preliminary biomarker data which provide insight into the on-mechanism immune stimulation which we believe are driving these responses."

Mr. Berlin continued, "Based on these results, we are expanding Part B, dose level 1, to enroll up to an additional 15 patients who have progressed on KEYTRUDA to further characterize the clinical activity of ADXS-503 in combination with KEYTRUDA as previously observed in the first two evaluable patients in this part of our study. In addition, we have opened enrollment in Part C to evaluate ADXS-503 in combination with KEYTRUDA as a first line treatment for patients with metastatic NSCLC that either have a high PD-L1 expression score and can receive KEYTRUDA alone or for patients who are ineligible to receive the standard of care regimen of KEYTRUDA in combination with platinum based-chemotherapy." He added, "The safety, tolerability and clinical activity observed so far supports the initiation of Part C for advanced patients in a first-line setting as well as the expansion of Part B in later treatment settings. Based on the clinical and immune correlative results to date, we are hopeful for enhanced responses to KEYTRUDA in patients in both of these settings who have limited treatment options and poor prognoses. We look forward to continued execution and the expansion of our HOT program to new indications including our planned Phase 1 study of ADXS-504 in prostate cancer patients with biochemical recurrence which we expect to enter the clinic by the end of this year."

Second Quarter Ended April 30, 2020 Financial Results

Research and development expenses for the second quarter of fiscal year 2020 were $3.9 million, compared with $6.0 million for the second quarter of fiscal year 2019. The decrease is largely attributable to the winding down of our Phase 3 AIM2CERV and Phase 1 ADXS-NEO studies as announced in June 2019 and October 2019, respectively.

General and administrative expenses for the three months ended April 30, 2020 were approximately $2.6 million compared to $3.1 million in the same three-month period in 2019. The decrease in expenses is mainly attributable to lower legal fees, and reduced employee and business development costs.

As of April 30, 2020, the Company had approximately $28.2 million in cash and cash equivalents. The Company believes this is sufficient capital to fund its obligations, as they become due, in the ordinary course of business until at least August 2021.

On June 11, 2020 Exelixis, Inc. (NASDAQ: EXEL) reported the initiation of CONTACT-01, a global phase 3 pivotal trial of cabozantinib (CABOMETYX) in combination with atezolizumab (TECENTRIQ) in patients with metastatic non-small cell lung cancer (NSCLC) who have been previously treated with an immune checkpoint inhibitor (ICI) and platinum-containing chemotherapy (Press release, Exelixis, JUN 11, 2020, View Source [SID1234561008]). Two additional phase 3 pivotal trials in metastatic castration-resistant prostate cancer (CRPC; CONTACT-02) and renal cell carcinoma (RCC; CONTACT-03) are planned as part of the clinical trial collaboration between Exelixis and Roche.

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"Survival rates for patients with metastatic non-small cell lung cancer are low, and since more than half of these patients are diagnosed at an advanced stage, the patient community is in need of new treatment options, especially for those who progress following immunotherapy and chemotherapy," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "We were pleased to see the positive results from cohort 7 of the COSMIC-021 trial further supporting the growing body of preclinical and clinical evidence that cabozantinib may promote a more immune-permissive environment potentially resulting in additive or synergistic effects with immune checkpoint inhibitors such as atezolizumab. We look forward to forthcoming findings for the combination in this disease in CONTACT-01, as well as in other difficult-to-treat cancers in planned phase 3 studies."

Results from the ongoing COSMIC-021 trial — a phase 1b study of cabozantinib and atezolizumab in multiple advanced solid tumors including NSCLC, CRPC and RCC — informed the design of this phase 3 pivotal trial. Initial results from the COSMIC-021 cohort of patients with advanced NSCLC who progressed after treatment with an ICI were presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program.

CONTACT-01 is a global, multicenter, randomized, phase 3, open-label study that aims to enroll approximately 350 patients. Patients will be randomized 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of docetaxel. The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival, objective response rate and duration of response. The trial is sponsored by Roche and co-funded by Exelixis.

About NSCLC

Lung cancer is the second most common type of cancer in the U.S., with more than 220,000 new cases expected to be diagnosed in 2020.1 The disease is the leading cause of cancer-related mortality in both men and women, causing 25% of all cancer-related deaths.1 The majority (84%) of lung cancer cases are NSCLC, which mainly comprise adenocarcinoma, squamous cell carcinoma and large cell carcinoma.1 The five-year survival rate for patients with NSCLC is 24%, but that rate falls to just 6% for those with advanced or metastatic disease.2 More than half of lung cancer cases are diagnosed at an advanced stage, and more options are needed for these patients.3

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide.

CABOMETYX in combination with atezolizumab is not indicated for previously treated metastatic non-small cell lung cancer.

About Exelixis’ Collaboration with Ipsen

On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. On December 21, 2016, this agreement was amended to include commercialization rights for Ipsen in Canada. Under the parties’ collaboration agreement, if Ipsen opts to participate in funding this phase 3 trial, or future studies, Ipsen will have access to the respective study results to support potential future regulatory submissions in their territory.

About Exelixis’ Collaboration with Takeda

On January 30, 2017, Exelixis and Takeda jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications in Japan. Under the parties’ collaboration agreement, if Takeda opts to participate in funding this phase 3 trial, or future studies, Takeda will have access to the respective study results to support potential future regulatory submissions in their territory.

Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

Important Safety Information

Warnings and Precautions

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.

Drug Interactions

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.