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Incyte Announces Initiation of Phase 3 RUXCOVID Study Evaluating Ruxolitinib (Jakafi®) as a Treatment for Patients with COVID-19 Associated Cytokine Storm

On Apr. 17, 2020 Incyte (Nasdaq:INCY) reported the initiation of RUXCOVID, a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of ruxolitinib (Jakafi) plus standard-of-care (SoC) in patients aged ≥12 years with COVID-19 associated cytokine storm. The collaborative study is sponsored by Incyte in the United States and Novartis outside of the United States.

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The composite primary endpoint is the proportion of patients who die, develop respiratory failure (require mechanical ventilation) or require intensive care unit (ICU) care by Day 29. Secondary endpoints comprise various efficacy assessments including evaluation of clinical status using a 9-point ordinal scale; in-hospital outcomes (mortality rate; proportion of patients requiring mechanical ventilation; duration of hospitalization, ICU stay, supplemental oxygen, invasive mechanical ventilation); change in the National Early Warning Score (NEWS2); change in SpO2/FiO2 ratio; proportion of patients with no oxygen therapy (oxygen saturation of ≥94% on room air); and safety. RUXCOVID will enroll approximately 400 patients globally.

Additionally, given the urgent nature of the COVID-19 pandemic, Incyte is also initiating a separate emergency Expanded Access Program (EAP) in the United States. The protocol will allow eligible patients with severe COVID-19 associated cytokine storm to receive ruxolitinib while it is being investigated for this indication.

"There is an unprecedented unmet medical need for treatments that prevent or reduce severe COVID-19 related complications to improve outcomes for patients and alleviate the overwhelming pressure on the global healthcare system," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We thank the FDA for the expedited review of the RUXCOVID study and hope to enroll this important clinical trial as quickly as possible to determine the potential utility of ruxolitinib for treatment of patients with severe COVID-19 associated cytokine storm."

RUXCOVID is the first Phase 3, randomized, placebo-controlled study designed to evaluate the efficacy and safety of ruxolitinib in patients with COVID-19 associated cytokine storm.

At present, there is ample commercial and clinical supply of ruxolitinib in the United States to meet the needs of U.S. patients receiving ruxolitinib in its approved indications and those participating in clinical trials. Incyte is increasing manufacturing efforts to respond to anticipated supply needs related to COVID-19 studies and working closely with distribution partners to monitor the supply of ruxolitinib.

About COVID-19 Associated Cytokine Storm
Cytokine storm is a severe immune overreaction that can be triggered by a viral infection and can lead to serious complications, including pneumonia and acute respiratory distress syndrome (ARDS). Patients with COVID-19 associated cytokine storm who experience these complications often require intensive care, including intubation and the use of mechanical ventilation, and are at an increased risk of mortality.

Emerging evidence suggests that regulating overactive signaling through the JAK-STAT pathway during a cytokine storm associated with COVID-19 could be a potential treatment approach, and it is hypothesized that ruxolitinib, a JAK1/JAK2 inhibitor, may be able to play a role in treating these patients.

Currently, there is limited clinical evidence on the safety and efficacy of ruxolitinib for the treatment of COVID-19 associated cytokine storm, and ruxolitinib is not FDA-approved for this use.

About RUXCOVID
RUXCOVID is a global, randomized, double-blind, placebo-controlled, 29-day, multi-center Phase 3 study evaluating the efficacy and safety of ruxolitinib plus standard of care (SoC) therapy in patients aged ≥12 years with COVID-19 associated cytokine storm compared to placebo plus SoC therapy.

The composite primary endpoint is the proportion of patients who die, develop respiratory failure (require mechanical ventilation), or require intensive care unit (ICU) care by Day 29. Secondary endpoints are comprised of various efficacy assessments including evaluation of clinical status using a 9-point ordinal scale; in-hospital outcomes (mortality rate; proportion of patients requiring mechanical ventilation; duration of hospitalization, ICU stay, supplemental oxygen, invasive mechanical ventilation); change in the National Early Warning Score (NEWS2); change in SpO2/FiO2 ratio; proportion of patients with no oxygen therapy (oxygen saturation of ≥94% on room air); and safety.

Eligible patients will be randomized 2:1 to receive oral ruxolitinib 5mg twice daily (BID) or oral-matching placebo for a total of 14 days. Study treatment will be given in combination with SoC therapy according to the investigator’s clinical judgement. After 14 days of therapy, should clinical signs or symptoms not improve or worsen, and the potential benefit outweighs the potential risks, patients may receive an additional 14 days of study therapy. In total, patients will be followed on study for 29 days post-randomization.

The RUXCOVID study is sponsored by Incyte in the United States, and Novartis outside of the United States.

About the Ruxolitinib Expanded Access Program (EAP) in COVID-19
The ruxolitinib Expanded Access Program (EAP) in COVID-19 for patients with severe COVID-19 associated cytokine storm allows eligible patients to receive ruxolitinib while it is being investigated in COVID-19 patients. Patients must be unable to participate in other clinical trials of ruxolitinib in COVID-19 to qualify for this EAP.

FDA Approves Incyte’s Pemazyre™ (pemigatinib) as First Targeted Treatment for Adults with Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma

On April 17, 2020 Incyte (Nasdaq:INCY) reported that the U.S. Food and Drug Administration (FDA) has approved Pemazyre (pemigatinib), a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test (Press release, Incyte, APR 17, 2020, View Source [SID1234556414]). Pemazyre is the first and only FDA-approved treatment for this indication, which was approved under accelerated approval based on overall response rate and duration of response (DOR). Continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial(s).

"Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades"

"Our research into FGFR2 fusions or rearrangements in cholangiocarcinoma and the development of Pemazyre as the first targeted treatment option demonstrates our commitment to translating scientific discovery into solutions that can positively impact patients’ lives," said Hervé Hoppenot, Chief Executive Officer, Incyte. "We’re proud to bring Pemazyre to patients and will make this new treatment available immediately."

The FDA approval was based on data from the FIGHT-202 study, a multi-center, open-label, single-arm study that evaluated Pemazyre as a treatment for adults with cholangiocarcinoma. In patients harboring FGFR2 fusions or rearrangements (Cohort A), Pemazyre monotherapy resulted in an overall response rate of 36% (primary endpoint), and median DOR of 9.1 months (secondary endpoint). Warnings and precautions for Pemazyre include eye problems such as dry or inflamed eyes, inflamed cornea, increased tears and a disorder of the retina; high levels of phosphate in the blood; and, for women who are pregnant, a risk of harm to the unborn baby or loss of pregnancy.

The FDA granted Pemazyre Breakthrough Therapy designation for the treatment of patients with previously treated advanced/metastatic or unresectable FGFR2 translocated cholangiocarcinoma. Additionally, the FDA granted Pemazyre Orphan Drug designation for the treatment of cholangiocarcinoma, and the New Drug Application (NDA) for Pemazyre was reviewed under the FDA’s Priority Review program.

"Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades,"1,2 said Ghassan Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center. "It is encouraging to have a new targeted treatment option for patients who historically have had limited options after first-line chemotherapy or surgery, in which relapse rates remain high."

Cholangiocarcinoma is a rare cancer that forms in the bile duct. It is classified based on its anatomical origin: intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. Patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor.3,4 The incidence of cholangiocarcinoma varies regionally and ranges between 0.3-3.4 per 100,000 in North America and Europe.3 FGFR2 fusions or rearrangements occur almost exclusively in iCCA, where they are observed in 10-16% of patients.5-7 FGFRs play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating fusions, rearrangements, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers.

"Today’s approval of Pemazyre provides an exciting new treatment option for patients and will bring hope to those who typically face a difficult diagnosis journey and poor prognosis," said Stacie Lindsey, President, Cholangiocarcinoma Foundation.

Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Pemazyre have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering patient support, including financial assistance and ongoing education and resources to eligible patients. More information is available at Pemazyre.com.

The FDA is also expected to approve FoundationOneCDx as the companion diagnostic for Pemazyre. FoundationOne CDx is Foundation Medicine’s comprehensive genomic profiling assay and broad companion diagnostic platform approved for all solid tumors. If approved, this companion diagnostic would help identify patients with FGFR2 fusions or rearrangements who may be eligible for Pemazyre.

Conference Call Information

Incyte will host an investor conference call and webcast on Monday, April 20, 2020, at 8:00 a.m. ET. The webcast will be available via investor.incyte.com.

To access the conference call, please dial 877-407-3042 for domestic callers or +1-201-389-0864 for international callers. When prompted, provide the conference identification number 13700772.

If you are unable to participate, a replay of the conference call will be available for 30 days. The replay dial-in number for the United States is 877-660-6853 and the dial-in number for international callers is +1-201-612-7415. To access the replay, you will need the conference identification number 13700772.

About FIGHT-202

The FIGHT-202 Phase 2 multi-center, open-label, single-arm study (NCT02924376) evaluated the safety and efficacy of Pemazyre – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGFR2 fusion or rearrangement.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg Pemazyre orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 was overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR in Cohorts B, A plus B, and C; and duration of response (DOR).

For more information about FIGHT-202, visit View Source

About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating the safety and efficacy of Pemazyre therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating Pemazyre in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type. FIGHT-205 is a Phase 2 study investigating Pemazyre plus pembrolizumab combination therapy and Pemazyre monotherapy in patients with previously untreated, metastatic or unresectable bladder cancer harboring FGFR3 mutations or fusions/rearrangements who are not eligible to receive cisplatin. FIGHT-302 is a Phase 3 study investigating Pemazyre as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About Pemazyre (pemigatinib)

Pemazyre is a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations.

Pemazyre is marketed by Incyte in the United States. Incyte has granted Innovent Biologics, Inc. rights to develop and commercialize pemigatinib in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan. Incyte has retained all other rights to develop and commercialize pemigatinib outside of the United States.

Additionally, Incyte’s marketing authorization application (MAA) seeking the approval of pemigatinib for patients with cholangiocarcinoma in the EU has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that is relapsed or refractory after at least one line of systemic therapy.

Pemazyre is a registered trademark of Incyte Corporation.

Important Safety Information

Before you take PEMAZYRE, tell your healthcare provider about all of your medical conditions, including if you:

have vision or eye problems
have problems swallowing tablets
are pregnant or plan to become pregnant. PEMAZYRE can harm your unborn baby or cause loss of your pregnancy (miscarriage). You should not become pregnant during treatment with PEMAZYRE.
Females who can become pregnant:

Your healthcare provider should do a pregnancy test before you start treatment with PEMAZYRE.
You should use an effective method of birth control during treatment and for 1 week after your final dose of PEMAZYRE. Talk to your healthcare provider about birth control methods that may be right for you.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant.
Males with female partners who can become pregnant:

You should use effective birth control when sexually active during treatment with PEMAZYRE and for 1 week after your final dose of PEMAZYRE.
are breastfeeding or plan to breastfeed. Do not breastfeed during treatment and for 1 week after your final dose of PEMAZYRE.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of PEMAZYRE?

PEMAZYRE may cause serious side effects, including:

Eye problems. Certain eye problems are common with PEMAZYRE but can also be serious. Eye problems include dry eye or inflamed eyes, inflamed cornea (front part of the eye), increased tears, and a disorder of the retina (an internal part of the eye). You will need to see an eye specialist for a complete eye exam before you begin treatment with PEMAZYRE, every 2 months for the first 6 months, and then every 3 months during treatment with PEMAZYRE.
You should use artificial tears or substitutes, hydrating or lubricating eye gels as needed, to help prevent or treat dry eyes.
Tell your healthcare provider right away if you develop any changes in your vision during treatment with PEMAZYRE, including: blurred vision, flashes of light, or see black spots. You may need to see an eye specialist right away.
High phosphate levels in your blood (hyperphosphatemia). Hyperphosphatemia is common with PEMAZYRE but can also be serious. Your healthcare provider will check your blood phosphate levels during treatment with PEMAZYRE.
Your healthcare provider may prescribe changes in your diet or phosphate lowering therapy, or change, interrupt, or stop PEMAZYRE if needed.
Tell your healthcare provider right away if you develop any muscle cramps, or numbness or tingling around your mouth.
The most common side effects of PEMAZYRE include:

hair loss
diarrhea
nails separate from the bed or poor formation of the nail
feeling tired
change in sense of taste
nausea
constipation
mouth sores
dry eyes
dry mouth
decrease in appetite
vomiting
joint pain
stomach-area (abdominal) pain
low phosphate in blood
back pain
dry skin
These are not all the possible side effects of PEMAZYRE. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Incyte Medical Information at 1-855-463-3463.

General information about the safe and effective use of PEMAZYRE.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PEMAZYRE for a condition for which it is not prescribed. Do not give PEMAZYRE to other people, even if they have the same symptoms you have. It may harm them. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information that is written for healthcare professionals. Keep PEMAZYRE and all medicines out of the reach of children.

Varian Announces Second Quarter Fiscal Year 2020 Earnings Release Date

On April 17, 2020 Varian (NYSE: VAR) reported its second quarter fiscal year 2020 earnings release date (Press release, Varian Medical Systems, APR 17, 2020, View Source [SID1234556412]).

The Company will report results for the second quarter of fiscal year 2020 after market close on Monday, May 4, 2020. The news release will be followed by a teleconference available to all interested at 1:30 p.m. Pacific Time. To access the teleconference call and replay:

Teleconference: Access from within the U.S. by dialing 1-877-869-3847, and from outside the U.S. by dialing 1-201-689-8261.

Replay: Access from within the U.S. by dialing 1-877-660-6853 and from outside the U.S. by dialing 1-201-612-7415 and enter conference ID 13700412. The teleconference replay will be available until 5:00 p.m. Pacific Time, Friday, May 8, 2020.

Webcast: To access the live webcast and replay, visit the company website at: www.varian.com/investors and click on the link for Second Quarter Earnings Results.

For automatic e-mail alerts regarding Varian news and events, investors can subscribe on the company website: View Source

Lantern Pharma IPO File Illuminates Plan to “Rescue” Failed Cancer Drugs

On April 17, 2020 Lantern reported that filed its IPO set a preliminary $28.8 million preliminary target for the proposed stock sale and says it has applied for a Nasdaq listing under the stock symbol "LTRN (Press release, Lantern Pharma, APR 17, 2020, View Source [SID1234556411])."

Lantern’s research aims to turn failed or abandoned drugs into new therapeutic candidates. The company says in its IPO filing that AI technology helps it find compounds best suited for such "drug rescue."

"This data-driven, genomically-targeted and biomarker-driven approach allows us to pursue a transformational drug development strategy that identifies, rescues or develops, and advances potential small molecule drug candidates at what we believe is a fraction of the time and cost associated with traditional cancer drug development," the company says in its filing.

Lantern calls its AI technology RADR. The company says the software includes millions of datapoints covering drug and tumor interactions, real-world information about thousands of cancer patients, results from clinical and drug sensitivity tests, and published cancer research. Lantern uses this software to identify the types of tumors and the groups of patients most likely to respond to treatment with its drugs.

The Lantern pipeline has three drugs. The most advanced program, LP-100, is in Phase 2 testing in prostate cancer. MGI Pharma advanced the drug to Phase 3 testing. But in 2002, the study was stopped after an early look at data suggested it was unlikely to beat chemotherapy. Lantern licensed the compound in 2015 and soon after sold the drug’s rights to European biotech Oncology Venture, according to the IPO filing. Oncology Venture is responsible for further clinical development of LP-100.

The most advanced Lantern compound being developed internally is LP-300, an experimental non-small cell lung cancer drug. The small molecule failed Phase 3 tests sponsored by BioNumerik Pharmaceuticals. In 2018, Lantern paid BioNumerik $25,000 up front to acquire LP-300 with an agreement to pay royalties if the drug reaches the market, according to the filing.

According to the IPO filing, Lantern’s retrospective analysis of the BioNumerik studies showed that some patients showed lived longer, particularly female non-smokers. Lantern says it plans to develop LP-300 for women who have never smoked or are currently non-smokers, as well as for non- or never-smokers whose genetics match up with a higher likelihood of responding to the treatment.

The third Lantern program, LP-184, was initially developed by MGI. The small molecule is currently in preclinical development for potential applications in several different types of cancer.

Lantern says it will use the cash raised from the IPO to fund Phase 2 tests of LP-300 and continue preclinical development of LP-184. The company also plans to continue developing its RADR technology and expand its drug pipeline by acquiring or licensing assets.

Lantern was founded in 2013 by Arunkumar Asaithambi and Biological Mimetics (BMI), a Frederick, MD-based developer of drugs for human and veterinary health. BMI owns 23.4 percent of Lantern and it also provides preclinical and non-clinical services to the company, according to the filing. Bios Equity Entities is Lantern’s largest shareholder, owning 42.1 percent.

Seattle Genetics Announces U.S. FDA Approval of TUKYSA™ (tucatinib) for People with Advanced Unresectable or Metastatic HER2-Positive Breast Cancer

On April 17, 2020 Seattle Genetics, Inc. (Nasdaq:SGEN) reported the U.S. Food and Drug Administration (FDA) granted approval to TUKYSA (tucatinib) tablets in combination with trastuzumab and capecitabine for adult patients with advanced unresectable (cannot be surgically removed) or metastatic HER2-positive breast cancer, including patients with brain metastases (disease that has spread to the brain), who have received one or more prior anti-HER2-based regimens in the metastatic setting (Press release, Seattle Genetics, APR 17, 2020, View Source [SID1234556408]). The FDA previously granted Breakthrough Therapy designation and Priority Review for TUKYSA and reviewed this application for approval under the Real-Time Oncology Review (RTOR) pilot program. The TUKYSA New Drug Application (NDA) is also part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities. TUKYSA is an oral, small molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.1,2

(Photo: Business Wire)
(Photo: Business Wire)

"With highly significant and clinically important results for overall and progression-free survival, the addition of TUKYSA to trastuzumab and capecitabine has the potential to become a standard of care for people with HER2-positive metastatic breast cancer after having received one or more previous anti-HER2 therapies in the metastatic setting," said Eric P. Winer, MD, Chief of the Division of Breast Oncology, Susan F. Smith Center for Women’s Cancers at Dana-Farber. "Cancer spreads to the brain in up to half of patients with HER2-positive metastatic breast cancer; and this approval is based on a unique clinical trial that included patients with active brain metastases, either untreated or progressing. TUKYSA is well tolerated by patients and is a valuable addition to the agents we have for HER2-positive metastatic breast cancer."

"We’re pleased to have collaborated with the FDA on our second expedited real-time oncology review, enabling us to rapidly bring this new targeted medicine to patients," said Clay Siegall, Ph.D., Chief Executive Officer at Seattle Genetics. "TUKYSA has shown impressive results in people with HER2-positive metastatic breast cancer, including in patients with active brain metastases, and offers patients an effective medicine following previous treatment with other anti-HER2 agents in the metastatic setting."

TUKYSA, in combination with trastuzumab and capecitabine, was evaluated in the trial HER2CLIMB, a randomized (2:1), double-blind, placebo-controlled trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). Forty-eight percent of patients in the study had a presence or history of brain metastases. The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the first 480 randomized patients.1 Additional efficacy outcome measures were evaluated in all randomized patients and included overall survival (OS), PFS in patients with a history or presence of brain metastases, and confirmed objective response rate (ORR).

Patients who received TUKYSA in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (PFS) compared to patients who received trastuzumab and capecitabine alone (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001). The addition of TUKYSA reduced the risk of death (OS) by 34 percent compared to trastuzumab and capecitabine alone (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048). Nearly twice the number of patients who received TUKYSA in combination with trastuzumab and capecitabine had a confirmed objective response compared to those who received trastuzumab and capecitabine alone (40.6 percent (95% CI: 35.3, 46.0) vs. 22.8 percent (95% CI: 16.7, 29.8); p=0.00008). For patients with brain metastases, the addition of TUKYSA reduced the risk of cancer progression or death (PFS) by 52 percent compared to trastuzumab and capecitabine alone (HR=0.48 [95% CI: 0.34, 0.69]; p<0.00001).

Serious adverse reactions occurred in 26 percent of patients who received TUKYSA. Serious adverse reactions occurring in 2 percent or more of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea, abdominal pain, and seizure (2% each). The most common adverse reactions occurring in 20 percent or more of patients who received TUKYSA were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Adverse reactions leading to treatment discontinuation occurred in 6 percent of patients who received TUKYSA; adverse reactions leading to treatment discontinuation of TUKYSA (in 1 percent or more of patients) were hepatotoxicity (1.5%) and diarrhea (1%).

The data were published in The New England Journal of Medicinein December 2019.

About TUKYSA (tucatinib)

TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.1

SeaGen Secure offers access and reimbursement support to help patients access TUKYSA. For more information, go to SeaGenSecure.com.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. An estimated 279,100 new cases of breast cancer will be diagnosed in the U.S. in 2020.3 Between 15 and 20 percent of breast cancer cases are HER2-positive.3 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.4,5,6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.7,8,9

Important Safety Information

Warnings and Precautions

Diarrhea – TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 12% with Grade 3 diarrhea and 0.5% with Grade 4 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.

If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
Hepatotoxicity – TUKYSA can cause severe hepatotoxicity. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 5% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients.

Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
Embryo-Fetal Toxicity – TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential risk to a fetus. Advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during TUKYSA treatment and for at least 1 week after the last dose.
Adverse Reactions

Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in ≥2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

Drug Interactions

Strong CYP3A or Moderate CYP2C8 Inducers: Concomitant use may decrease TUKYSA activity. Avoid concomitant use of TUKYSA.
Strong or Moderate CYP2C8 Inhibitors: Concomitant use of TUKYSA with a strong CYP2C8 inhibitor may increase the risk of TUKYSA toxicity; avoid concomitant use. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.
CYP3A Substrates: Concomitant use may increase the toxicity associated with a CYP3A substrate. Avoid concomitant use of TUKYSA where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage.
P-gp Substrates: Concomitant use may increase the toxicity associated with a P-gp substrate. Consider reducing the dosage of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity.
Use in Specific Populations

Lactation: Advise women not to breastfeed while taking TUKYSA and for at least 1 week after the last dose.
Renal Impairment: Use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr < 30 mL/min), because capecitabine is contraindicated in patients with severe renal impairment.
Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.
For more information, please see the full Prescribing Information for TUKYSA here.

Conference Call Details

Seattle Genetics’ management will host a conference call and webcast to discuss the approval of TUKYSA today at 1:00 p.m. Pacific Time (PT); 4:00 p.m. Eastern Time (ET). The live event will be simultaneously webcast and available for replay from the Seattle Genetics website at www.seattlegenetics.com, under the Investors section. Investors may also participate in the conference call by calling 888-220-8451 (domestic) or 323-794-2588 (international). The conference ID is 5796578. A replay of the audio only will be available by calling 888-203-1112 (domestic) or 719-457-0820 (international), using conference ID 5796578. The telephone replay will be available until 5:00 p.m. PT on April 20, 2020.