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Immunocore presents ovarian cancer expansion data for ImmTAC® candidate IMC-C103C targeting MAGE-A4

On December 8, 2022 Immunocore Holdings plc (Nasdaq: IMCR), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, autoimmune and infectious diseases, reported data for IMC-C103C, a bispecific T cell engager targeting MAGE-A4, in patients with ovarian cancer (Press release, Immunocore, DEC 8, 2022, View Source [SID1234624953]).

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The Phase 1 data, presented in a poster at the ESMO (Free ESMO Whitepaper) Immuno-Oncology 2022 Congress, include 33 heavily pre-treated patients with ovarian cancer, who received doses of ≥ 90 mcg intravenously. This includes 16 new patients, and 17 patients previously reported at the ESMO (Free ESMO Whitepaper) Immuno-Oncology 2021 Congress, now with longer follow-up. All patients had platinum relapsed/refractory ovarian cancer (70% PARP inhibitors experienced) and were enrolled regardless of MAGE-A4 protein expression, which was analyzed retrospectively.

Of the 33 patients, 39% (13/33) were MAGE-A4 negative as measured by immunohistochemistry (IHC), and 2 patients had an unknown H score. Of the 55% (18/33) MAGE-A4 positive patients, the majority had low expression (median score = 29 of 300), and only 2 had an H score > 150.

The safety profile was consistent with that reported previously and the mechanism of action, i.e., T cell activation. No related AE led to treatment discontinuation or death.

At the time of data cut-off, 32 patients were evaluable for response, with one additional patient (H score 21) still on treatment and not having had first tumor assessment. Of the 17 evaluable MAGE-A4 positive patients, one had a durable Partial Response (PR), with a duration of 12.7 months, one patient who had a Stable Disease (SD) converted to an unconfirmed PR after the poster data cutoff date and is still ongoing, and 5 had SD. Reductions in ctDNA were observed in over half of ctDNA evaluable patients (12/22), including 7 with ≥ 50% reductions, and even in those with low or zero MAGE-A4 expression.

"Immunocore has learned from tebentafusp that OS benefit and ctDNA reduction are observed in patients with both high and low total protein expression, while RECIST responses are enriched at higher protein expression," said David Berman, Head of Research and Development of Immunocore. "The emerging IMC-C103C results, where most patients had either no or very low MAGE-A4 expression, are consistent with the RECIST and ctDNA reduction results reported for tebentafusp."

IMC-C103C is part of a co-development / co-promotion collaboration with Genentech, a member of the Roche Group under which Immunocore shares program costs and profits equally. Both companies are evaluating next steps for the IMC-C103C program.

Guardant Health Announces Collaboration With AstraZeneca to Develop Companion Diagnostic to Identify Patients With ESR1-mutated Metastatic Breast Cancer

On December 8, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that it has entered into a collaboration with AstraZeneca to pursue the development, regulatory approval and commercialization of the Guardant360 CDx blood test as a companion diagnostic to identify patients with ESR1-mutated metastatic breast cancer (Press release, Guardant Health, DEC 8, 2022, View Source [SID1234624952]). The initiative is part of a larger strategic collaboration investigating the use of liquid biopsy as a tool to inform early therapy intervention.

The collaboration is one of the first to explore the potential of a comprehensive genomic profiling ctDNA (circulating tumor DNA) assay to identify mutation-driven resistance to a prior line of therapy in metastatic breast cancer. The Guardant360 CDx liquid biopsy test is being used to identify patients with detectable ESR1mutations in the SERENA-6 phase III clinical trial, which is evaluating camizestrant, a next-generation oral selective estrogen receptor degrader (ngSERD) being developed by AstraZeneca, in combination with CDK4/6 inhibitors versus aromatase inhibitors in combination with CDK4/6 inhibitors in patients with HR-positive, HER2-negative metastatic breast cancer.

"We’re pleased to collaborate with AstraZeneca on this important study for breast cancer patients," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "We look forward to exploring the potential benefit of early comprehensive genomic profiling using a simple blood draw, which can provide faster results than a tissue biopsy and enable clinicians to consider earlier intervention with the goal of achieving improved patient outcomes."

About Guardant Health

Guardant Health is a leading precision oncology company focused on helping conquer cancer globally through use of its proprietary tests, vast data sets and advanced analytics. The Guardant Health oncology platform leverages capabilities to drive commercial adoption, improve patient clinical outcomes and lower healthcare costs across all stages of the cancer care continuum. Guardant Health has commercially launched Guardant360, Guardant360 CDx, Guardant360 TissueNext, Guardant360 Response, and GuardantOMNI tests for advanced stage cancer patients, and Guardant Reveal for early-stage cancer patients. The Guardant Health screening portfolio, including the ShieldTM test, aims to address the needs of individuals eligible for cancer screening. For more information, visit guardanthealth.com and follow the company on LinkedIn and Twitter.

Entry Into a Material Definitive Agreement

On December 6, 2022, iBio, Inc. (the "Company") entered into an underwriting agreement (the "Underwriting Agreement") with H.C. Wainwright & Co., LLC ("Wainwright"). Pursuant to the Underwriting Agreement, the Company agreed to sell to Wainwright, in a firm commitment underwritten offering (the "Offering") (i) 1,530,769 shares of the Company’s Common Stock, par value $0.001 per share (the "Common Stock"), (ii) pre-funded warrants (the "Pre-Funded Warrants") to purchase up to 1,834,616 shares of Common Stock, (iii) Series A Common Stock purchase warrants (the "Series A Warrants") to purchase up to 3,365,385 shares of Common Stock and (iv) Series B Common Stock purchase warrants (the "Series B Warrants" and together with the Series A Warrants, the "Common Warrants") to purchase up to 3,365,385 shares of Common Stock (Filing, 8-K, iBioPharma, DEC 8, 2022, View Source [SID1234624950]).

The combined purchase price of each share of Common Stock and the accompanying Common Stock Warrants is $1.04 and the combined purchase price of each Pre-Funded Warrant and the accompanying Common Stock Warrants is $1.039, which is equal to the combined purchase price per share of Common Stock and accompanying Common Stock Warrants, minus the exercise price of each Pre-Funded Warrant of $0.001. Each share of Common Stock and Pre-Funded Warrant, as applicable, is being sold together with one Series A Warrant to purchase one share of Common Stock and one Series B Warrant to purchase one share of Common Stock. The Series A Warrants and the Series B Warrants have an exercise price of $1.04 per share and are immediately exercisable. The Series A Warrants will expire five (5) years from the date of issuance and the Series B Warrants will expire twenty-four (24) months from the date of issuance. There is not expected to be any trading market for the Pre-Funded Warrants or the Common Stock Warrants issued in the Offering.

Pursuant to the Underwriting Agreement, the Company has granted Wainwright a 30-day option to purchase up to an additional 504,807 shares of Common Stock and/or Common Warrants to purchase up to an additional 1,009,614 shares of Common Stock at the public offering price, less the underwriting discounts and commissions, solely to cover over-allotments. The Company has also agreed to issue to Wainwright, as the representative of the underwriters, warrants (the "Representative’s Warrants") to purchase a number of shares of Common Stock equal to 6.0% of the aggregate number of shares of Common Stock and Pre-Funded Warrants being offered in the Offering at an exercise price equal to $1.30, which is 125% of the combined public offering price per share of Common Stock and the accompanying Common Stock Warrants, and to reimburse the underwriter for certain Offering-related expenses. The Representative’s Warrants may be exercised on a cashless basis if an effective registration statement is not available and will expire five years after the commencement of sales of the securities in the Offering.

The closing of the Offering is expected to occur on or about December 9, 2022, subject to the satisfaction of customary closing conditions.

The net proceeds from the Offering, after deducting underwriting discounts and commissions and other estimated offering expenses payable by the Company and excluding the net proceeds, if any, from the exercise of the Common Stock Warrants, are approximately $2.9 million (or $3.4 million if Wainwright exercises its option to purchase additional shares of Common Stock and Common Stock Warrants in full). The Company intends to use the net proceeds from the Offering primarily for operating costs, including for research and development and other trial preparation expenses in addition to working capital needs and for other general corporate purposes, which may include retention and severance payments to certain of the Company’s employees or former employees. The Company may also use a portion of the net proceeds to invest in or acquire other products, businesses or technologies, although it has no commitments or agreements with respect to any such investments or acquisitions as of the date hereof. In addition, the Company intends to use a portion of the net proceeds from the Offering to pay principal payments of $250,000 per month in debt amortization on a monthly basis through March 2023 pursuant to the terms of its amended Credit Agreement with Woodforest National Bank.

Wainwright acted as the sole book-running manager for the Offering. The Company paid Wainwright an underwriting discount equal to 7.0% of the gross proceeds of the Offering, and reimbursed Wainwright for the legal fees and certain expenses of the underwriter, in the sum of up to $100,000, in connection with this offering, up to $20,000 for certain clearance fees and settlement expenses and $25,000 for non-accountable expenses.

All securities offered and sold in the Offering (including the shares of Common Stock issuable from time to time upon exercise of the Pre-Funded Warrants, the Series A Warrants, the Series B Warrants and the Representative’s Warrants) were offered pursuant to the Company’s effective Registration Statement on Form S-3 (Registration No. 333-250973), including a base prospectus contained therein dated December 7, 2020, as supplemented by a prospectus supplement relating to the Offering, dated December 6, 2022, and filed with the Securities and Exchange Commission on the date of this Current Report on Form 8-K.

The Underwriting Agreement contains customary representations, warranties, and covenants of the Company and also provides for customary indemnification by each of the Company and Wainwright against certain liabilities and customary contribution provisions in respect of those liabilities.

The description of terms and conditions of the Underwriting Agreement does not purport to be complete and is qualified in its entirety by the full text of the Underwriting Agreement, a copy of which is attached hereto as Exhibit 1.1.

A copy of the opinion of Blank Rome LLP relating to the legality of the issuance and sale of the securities sold in the Offering is attached as Exhibit 5.1 hereto.

Terms of the Pre-Funded Warrants, Series A Warrants and Series B Warrants

The Pre-Funded Warrants were offered in lieu of shares of Common Stock to certain investors because the purchase of shares of Common Stock in the Offering would otherwise result in said investors, together with their affiliates and certain related parties, beneficially owning more than 4.99% (or, at the election of the Investor, 9.99%) of the Company’s outstanding Common Stock immediately following the consummation of the Offering. Each Pre-Funded Warrant is exercisable for one share of Common Stock at an exercise price of $0.001 per share. The Pre-Funded Warrants are immediately exercisable and may be exercised at any time until all of the Pre-Funded Warrants are exercised in full.

Each Series A Warrant and Series B Warrant offered hereby will be a Warrant to purchase one share of Common Stock and will have an initial exercise price equal to $1.04 per share. The Series A Warrants will be immediately exercisable and will expire five years from the date of issuance. The Series B Warrants will be immediately exercisable and will expire twenty-four months from the date of issuance. The exercise price and number of shares of Common Stock issuable upon exercise of the Series A Warrants and Series B Warrants is subject to appropriate adjustment in the event of share dividends, share splits, reorganizations or similar events affecting the Common Stock and the exercise price.

A holder (together with its affiliates) of the Common Stock Warrants or Pre-Funded Warrants may not exercise any portion of the Common Stock Warrants or Pre-Funded Warrants, as applicable, to the extent that the holder would own more than 4.99% (or, at the holder’s option upon issuance, 9.99%) of the Company’s outstanding Common Stock immediately after exercise, as such percentage ownership is determined in accordance with the terms of the Common Stock Warrants or Pre-Funded Warrants, as applicable. In lieu of making the cash payment otherwise contemplated to be made to the Company upon exercise of a Common Stock Warrant in payment of the aggregate exercise price, the holder may elect instead to receive upon such exercise (either in whole or in part) the net number of shares of Common Stock determined according to a formula set forth in the Common Stock Warrants, provided that such cashless exercise shall only be permitted if the Registration Statement is not effective at the time of such exercise or if the prospectus to which the Registration Statement is a part is not available for the issuance of shares of Common Stock to the Common Stock Warrant holder. In addition, in certain circumstances, upon a fundamental transaction (as defined in the Common Stock Warrants), the holder will have the right to require the Company to repurchase the Common Stock Warrants at the Black Scholes Value (as defined in the Common Stock Warrants); provided, however, that, if the fundamental transaction is not within the Company’s control, including not approved by the Company’s board of directors, then the holder shall only be entitled to receive the same type or form of consideration (and in the same proportion), at the Black Scholes Value of the unexercised portion of the Common Stock Warrants, that is being offered and paid to the holders of Common Stock of the Company in connection with the fundamental transaction.

In lieu of making the cash payment otherwise contemplated to be made to the Company upon exercise of a Pre-Funded Warrant in payment of the aggregate exercise price, the holder may elect instead to receive upon such exercise (either in whole or in part) the net number of shares of Common Stock determined according to a formula set forth in the Pre-Funded Warrants.

The description of terms and conditions of the Pre-Funded Warrants, Series A Warrants, Series B Warrants and Representative’s Warrants do not purport to be complete and are qualified in their entirety by the full text of the form of such Pre-Funded Warrants, Series A Warrants, Series B Warrants and Representative’s Warrants, copies of which are attached hereto as Exhibits 4.1, 4.2, 4.3 and 4.4, respectively.

Fresenius Kabi expands injectable oncology portfolio in the U.S.

On December 8, 2022 Fresenius Kabi reported that it has introduced Pralatrexate Injection, a drug for the treatment of relapsed or refractory peripheral T-cell lymphoma in the U.S. Fresenius Kabi Pralatrexate Injection that is a generic of Folotyn and is available to customers immediately (Press release, Fresenius, DEC 8, 2022, View Source [SID1234624949]). It is the newest addition to the company’s injectable oncology medicine portfolio, the largest in U.S. health care.

Exelixis Provides Update on Phase 3 CONTACT-01 Trial Evaluating Cabozantinib in Combination with Atezolizumab in Patients with Metastatic Non-Small Cell Lung Cancer Previously Treated with Immunotherapy and Chemotherapy

On December 8, 2022 Exelixis, Inc. (Nasdaq: EXEL) reported that the CONTACT-01 study did not meet its primary endpoint of overall survival at the final analysis. CONTACT-01 is a phase 3 trial evaluating cabozantinib (CABOMETYX) in combination with atezolizumab (TECENTRIQ) versus docetaxel in patients with metastatic non-small cell lung cancer (NSCLC) without actionable mutations who experienced disease progression on or after treatment with an immune checkpoint inhibitor and platinum-containing chemotherapy (Press release, Exelixis, DEC 8, 2022, View Source [SID1234624948]).

The safety profile of the combination of cabozantinib and atezolizumab observed in the trial was consistent with the known safety profiles for each single agent, and no new safety signals were identified. Detailed findings from CONTACT-01 will be submitted for presentation at a future medical meeting.

About CONTACT-01

CONTACT-01 is a global, multicenter, randomized, phase 3, open-label study that enrolled 366 patients who were randomized 1:1 to the experimental arm of cabozantinib in combination with atezolizumab and the control arm of docetaxel. The study enrolled patients with both squamous and non-squamous NSCLC who progressed during or following anti-PD-1/PD-L1 therapy administered either concurrently or sequentially with chemotherapy. The primary endpoint of the trial was overall survival. Secondary endpoints included progression-free survival, objective response rate and duration of response. Results from cohort 7 of the phase 1b COSMIC-021 trial informed the CONTACT-01 trial design. CONTACT-01 was sponsored by Roche and co-funded by Exelixis. Both Ipsen and Takeda Pharmaceutical Company Limited (Takeda) opted in to participate in the trial and are contributing to the funding for this study under the terms of the companies’ respective collaboration agreements with Exelixis. More information about the trial is available at ClinicalTrials.gov.

About NSCLC

Lung cancer is a leading cause of cancer death globally.1 Every year, almost 1.8 million people die from the disease.1 In the U.S., lung cancer is the second most common type of cancer, with more than 236,000 new cases expected to be diagnosed in 2022.2 The majority (84%) of lung cancer cases are NSCLC.3 The overall five-year survival rate for patients with NSCLC is 26%, but that rate falls to just 7% for those with advanced or metastatic disease.4 More than half of lung cancer cases are diagnosed when metastatic.5

Cancer immunotherapy alone or in combination with platinum-containing chemotherapy is a standard of care treatment in first- and second-line NSCLC.6 However, people who progress after this initial therapy have limited treatment options and survival outcomes remain poor.5,6,7

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

CABOMETYX in combination with atezolizumab is not indicated as a treatment for NSCLC.

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, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, 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 events that require medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% 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. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients. Grade 3 diarrhea occurred in 10% of CABOMETYX patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1, resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 45% 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.

Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab. Withhold and resume at a reduced dose based on severity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria, resume CABOMETYX at a reduced dose. 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, resume at a reduced dose.

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. 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.

Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in 19% of patients treated with CABOMETYX, including Grade 3 in 0.4% of patients.

Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated.

Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in 13% of patients treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1% of patients. Laboratory abnormality data were not collected in CABOSUN.

In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients.

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

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 common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

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. Avoid CABOMETYX in patients with severe hepatic impairment.

Please see accompanying full Prescribing Information View Source

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.