On April 15, 2020 UroGen Pharma Ltd. (Nasdaq: URGN) reported the U.S. Food and Drug Administration (FDA) granted expedited approval for Jelmyto(mitomycin) for pyelocalyceal solution, a first-in-class treatment indicated for adults with low-grade upper tract urothelial cancer (LG UTUC) (Press release, UroGen Pharma, APR 15, 2020, View Source [SID1234556352]). This landmark approval is based on positive results from the Phase 3 OLYMPUS trial that showed Jelmyto provides an effective, kidney-sparing option for patients with this rare and difficult-to-treat cancer.

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Jelmyto consists of mitomycin, an established chemotherapy, and sterile hydrogel, using UroGen’s proprietary sustained release RTGel technology. It has been designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means.

"UroGen was founded on the vision to improve lives by challenging the current standard of care. Jelmyto, which leverages our innovative technology and expertise in specialty cancers and urologic diseases, is just the beginning as we build a company focused on bringing novel solutions to patients," said Liz Barrett, President and Chief Executive Officer, UroGen. "We thank the patients and researchers involved in our OLYMPUS trial for helping us advance a transformative treatment in a disease space that has been historically ignored. We are tremendously proud to have pioneered this first-in-class therapy that improves patient care in a difficult-to-treat cancer."

LG UTUC is a rare cancer that develops in the lining of the upper urinary tract, ureters and kidneys. In the U.S., there are approximately 6,000 – 7,000 new or recurrent LG UTUC patients annually. It is a challenging condition to treat due to the complex anatomy of the urinary tract system. The current standard of care includes multiple surgeries and most patients require a radical nephroureterectomy, which includes the removal of the renal pelvis, kidney, ureter and bladder cuff.1 Treatment is further complicated by the fact that LG UTUC is most commonly diagnosed in patients over 70 years of age, who may already have compromised kidney functionality and may suffer further complications as a result of major surgery.

"Jelmyto offers a new, non-surgical treatment approach for patients who otherwise may require treatment by radical nephroureterectomy, which is associated with declining kidney function and other complications," said Dr. Seth Lerner, M.D., FACS, Professor of Urology at Baylor College of Medicine in Houston, TX and Principal Investigator of the OLYMPUS trial. "This novel, minimally invasive, kidney-sparing treatment has the potential to transform the way low-grade upper tract urothelial cancer is treated and help patients avoid long-term complications associated with surgery and the loss of their kidney."

The FDA approval is based on results from the Phase 3 OLYMPUS trial showing Jelmyto achieved clinically significant disease eradication in adults with LG UTUC.Findings include:

Complete response (CR) (primary endpoint) of 58% in the intent-to-treat population and in the sub-population of patients who were deemed not capable of surgical removal at diagnosis.
At the 12-month time point for assessment of durability, 19 patients remained in CR, seven had experienced recurrence of disease and nine patients continued to be followed for the 12-month duration of response.
Kaplan-Meier analysis estimated 12-month durability at 84%2 (based on interim data).
The most commonly reported adverse events (≥ 20%) were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Most adverse events were mild to moderate and manageable using well established treatments. No treatment-related deaths occurred.
"There has been little progress for decades in the treatment of low-grade upper tract urothelial cancer, and this new option is paradigm-shifting for patients who often face recurrence and major surgery to remove their kidney," said Andrea Maddox-Smith, Chief Executive Officer, Bladder Cancer Advocacy Network. "We applaud the FDA approval and the impact it will have for this community of elderly patients, many of whom struggle with comorbidities and have been hoping for a surgery-free treatment option."

UroGen is committed to helping patients access Jelmyto. UroGen Support may help identify appropriate financial assistance programs for patients with commercial, Medicare or Medicaid coverage, as well as those with no insurance coverage. These programs are for eligible patients who have been prescribed Jelmyto and who need help managing the cost of treatment. The appropriate program will depend on the patient’s coverage. Visit View Source or contact UroGen Support at 855-JELMYTO for additional information.

The FDA evaluated Jelmyto under Priority Review, which is reserved for medicines that may represent significant improvements in safety or efficacy in treating serious conditions. Jelmyto was also granted Breakthrough Therapy designation by the FDA, which was created to expedite the development and review of drugs developed for serious or life-threatening conditions with high unmet need.

Conference Call & Webcast Information

Members of UroGen’s management team will host a live conference call and webcast on April 16 at 8:30 AM Eastern Time to review Jelmyto (mitomycin) for pyelocalyceal solution approval details and commercialization plans. The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call (855) 765-5685 (U.S.) or (615) 247-5916 (International) to listen to the live conference call. The conference ID number for the live call is 7864846. An archive of the webcast will be available for two weeks on the Company’s website.

About the Phase 3 OLYMPUS Trial

OLYMPUS (Optimized DeLivery of Mitomycin for Primary UTUC Study) is an open-label, single-arm Phase 3 clinical trial of Jelmyto (mitomycin) for pyelocalyceal solution to evaluate the safety, tolerability and tumor ablative effect of Jelmyto in patients with low-grade upper tract urothelial cancer (UTUC). The trial enrolled 74 patients at clinical sites across the U.S. and Israel. Study participants were treated with six weekly instillations of Jelmyto administered via a standard catheter. Four to six weeks following the last instillation, patients underwent a Primary Disease Evaluation (PDE) to determine complete response (CR), the primary endpoint of the study. PDE involved a ureteroscopy and wash cytology, a standard microscopic test of cells obtained from the urine to detect cancer. Patients who achieved a CR at the PDE timepoint were then followed for up to 12 months to determine the durability of response with Jelmyto.

About Jelmyto (mitomycin) for pyelocalyceal solution

Jelmyto (mitomycin) for pyelocalyceal solution is a drug formulation of mitomycin for the treatment of low-grade upper tract urothelial cancer (LG UTUC). Utilizing the RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, Jelmyto is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. Jelmyto is delivered to patients using standard ureteral catheters. The U.S. Food and Drug Administration granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to Jelmyto for the treatment of LG UTUC. Jelmyto is the first drug approved for the treatment of LG UTUC.

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO.
Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose.
Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.
are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: side pain, urinary tract infection, blood in your urine, kidney problems, tiredness, nausea, stomach pain, trouble with urination, vomiting, low red blood cell count, frequent urination, itching, chills, and fever.

Please see JELMYTO Full Prescribing Information, including the Patient Information, for additional information.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and 10 percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as upper tract urothelial cancers (UTUC). In the U.S., there are approximately 6,000 – 7,000 new or recurrent low-grade UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse.

On April 15, 2020 AIkido Pharma Inc. (AIKI) ("AIkido" or the "Company"), a technology development company committed to the fostering of innovative ideas, reported the closing of its previously announced registered direct offering with several institutional and accredited investors of 14,000,000 shares of its common stock at a purchase price of $1.00 per share, priced at-the-market under Nasdaq rules (Press release, Spherix, APR 15, 2020, View Source [SID1234556350]). The gross proceeds to the Company from the offering totaled $14.0 million, before deducting placement agent fees and other offering expenses.

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H.C. Wainwright & Co., LLC acted as the exclusive placement agent for the offering.

The Company intends to use the net proceeds from the offering for working capital and general corporate purposes.

The shares of common stock described above were offered by AIkido pursuant to a shelf registration statement on Form S-3 (No. 333-220632), which was previously declared effective by the Securities and Exchange Commission ("SEC"). A final prospectus supplement and the accompanying prospectus relating to the common shares was filed by AIkido with the SEC and can be obtained at the SEC’s website at View Source Electronic copies of the final prospectus supplement and the accompanying prospectus relating to the registered direct offering may also be obtained by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, New York, New York 10022, by email at [email protected] or by phone at (646) 975-6996.

This press release does not constitute an offer to buy nor will there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On April 15, 2020 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that it has entered into an agreement with Memorial Sloan Kettering Cancer Center ("MSK") and Massachusetts Institute of Technology ("MIT") for a worldwide exclusive license and research collaboration to develop and commercialize antibody constructs based on the SADA-BiDE (2-step Self-Assembly and DisAssembly-Bispecific DOTA-Engaging antibody system) Pre-targeted Radioimmunotherapy Platform (the "SADA technology"), a concept also referred to as Liquid RadiationTM (Press release, Y-mAbs Therapeutics, APR 15, 2020, View Source [SID1234556349]).

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The SADA technology utilizes a targeted payload delivery method where antibody constructs assemble in tetramers and bind to the tumor target. Unbound constructs predictably disassemble into smaller antibody fragments and are excreted through the kidneys within hours after administration. In a second infusion, a radioactive payload binds to the antibody constructs to radiate the tumor. The SADA technology was invented by Nai-Kong V. Cheung, M.D., Ph.D., Mahiuddin Ahmed, Ph.D. and Brian Santich, Ph.D. and adapted for radioimmunotherapy by Steven M. Larson, M.D. and Sarah Cheal, Ph.D., all current or former MSK employees.

Under the license, Y-mAbs will initiate development of a number of constructs developed by MSK and will advance a series of the Company’s proprietary constructs. The SADA technology will also be available for sublicensing.

"I am excited to enter into this agreement with MSK and MIT to expand Y-mAbs’ antibody platform with this promising technology. We believe the SADA technology represents a new approach to pre-targeted radioimmunotherapy, which may have the potential to improve the current treatment landscape, since it enhances the therapeutic index of payload delivery," stated Thomas Gad, Founder, Chairman, President and Head of Business Development and Strategy.

Dr. Claus Moller, Chief Executive Officer, continued, "We believe the SADA technology takes radioconjugated antibody constructs to a new level and opens a much broader usage than any other radiolabeling technology in the antibody area. The pre-targeted approach means that we expect to deliver higher doses of radiation directly to the tumor while minimizing the exposure to normal tissues. I don’t believe the tumor-to-blood standard uptake ratios obtained in animal models based on the SADA technology have ever been seen before."

On April 15, 2020 BioXcel Therapeutics Presented the corporate Presentation (Presentation, BioXcel Therapeutics, APR 15, 2020, View Source [SID1234556348]).

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On April 15, 2020 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported the U.S. launch of ONTRUZANT (trastuzumab-dttb), as a biosimilar of the reference biologic medicine Herceptin (Press release, Merck & Co, APR 15, 2020, View Source [SID1234556347]). ONTRUZANT is available in both 150 mg single-dose vials and 420 mg multiple-dose vials.

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ONTRUZANT will be introduced in the U.S. at a list price (wholesaler acquisition cost) of approximately $1,325 for the 150 mg single-dose vial and $3,709 for the 420 mg multiple-dose vial (prices are rounded), representing a 15% discount to the current list price of Herceptin. Wholesaler acquisition costs do not include discounts to payers, providers, distributors and other purchasing organizations.

ONTRUZANT is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature) breast cancer as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; as a single agent following multi-modality anthracycline based therapy. Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product. Serious and sometimes fatal side effects have been reported with trastuzumab products. Subclinical and clinical cardiac failure have been reported. The incidence and severity were highest in patients receiving trastuzumab with anthracycline-containing regimens. Discontinue ONTRUZANT treatment for cardiomyopathy. Administration of ONTRUZANT can result in serious and fatal infusion reactions and pulmonary toxicity. Discontinue ONTRUZANT for anaphylaxis, angioedema, interstitial pneumonitis or acute respiratory distress syndrome. Exposure to ONTRUZANT during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death. Exacerbation of chemotherapy-induced neutropenia can also occur. Detection of HER2 protein overexpression is necessary for selection of patients appropriate for ONTRUZANT therapy.

ONTRUZANT is being launched in the U.S. by Merck as part of a development and commercialization agreement with Samsung Bioepis. Under terms of the agreement, Samsung Bioepis is responsible for preclinical and clinical development, process development and manufacturing, clinical trials and regulatory registration. Merck will be responsible for all commercialization activities for products approved in its partnered territories, including the U.S.

ONTRUZANT was approved by the FDA in January 2019 based on the review of Samsung Bioepis’ comprehensive data package, which included extensive structural and functional analytical data, nonclinical and clinical pharmacokinetic data, and a comparative clinical study demonstrating that ONTRUZANT is highly similar to its reference product, Herceptin, in terms of the safety, purity and potency of the product.

On Feb. 5, 2020, Merck announced that it intends to spin-off products from its Women’s Health, trusted Legacy Brands and Biosimilars businesses, including ONTRUZANT, into a new, independent, publicly-traded company. Merck will continue to fully support the commercialization of ONTRUZANT until the spinoff, which is intended to take place in the first half of 2021, at which time ONTRUZANT will become a product of the new company.

ONTRUZANT Indications and Usage

Adjuvant Breast Cancer

ONTRUZANT is indicated for adjuvant treatment of HER2-overexpressing node-positive or node negative (ER/PR-negative or with one high-risk feature) breast cancer:

As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
As part of a treatment regimen with docetaxel and carboplatin
As a single agent following multimodality anthracycline-based therapy
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Breast Cancer

ONTRUZANT is indicated:

In combination with paclitaxel for the first-line treatment of HER2-overexpressing metastatic breast cancer
As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Gastric Cancer

ONTRUZANT is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Selected Safety Information

Cardiomyopathy

Administration of trastuzumab products can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving a trastuzumab product with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed congestive heart failure (CHF) died of cardiomyopathy.
Evaluate left ventricular function in all patients prior to and during treatment with ONTRUZANT. Discontinue ONTRUZANT treatment in patients receiving adjuvant therapy and withhold ONTRUZANT in patients with metastatic disease for clinically significant decrease in left ventricular function.
Infusion Reactions; Pulmonary Toxicity

Administration of trastuzumab products can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of administration. Interrupt ONTRUZANT infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue ONTRUZANT for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
Embryo-Fetal Toxicity

Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.
Warnings and Precautions

Cardiomyopathy

Trastuzumab products can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Trastuzumab products can also cause asymptomatic decline in left ventricular ejection fraction (LVEF).

There is a 4 to 6-fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving trastuzumab products as a single agent or in combination therapy compared with those not receiving trastuzumab products. The highest absolute incidence occurs when a trastuzumab product is administered with an anthracycline.

Withhold ONTRUZANT for ≥ 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values. The safety of continuation or resumption of ONTRUZANT in patients with trastuzumab product-induced left ventricular cardiac dysfunction has not been studied.

Patients who receive anthracycline after stopping ONTRUZANT may also be at increased risk of cardiac dysfunction.

Cardiac Monitoring: Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended:

Baseline LVEF measurement immediately prior to initiation of ONTRUZANT
LVEF measurements every 3 months during and upon completion of ONTRUZANT
Repeat LVEF measurement at 4-week intervals if ONTRUZANT is withheld for significant left ventricular cardiac dysfunction.
LVEF measurements every 6 months for at least 2 years following completion of ONTRUZANT as a component of adjuvant therapy.
Infusion Reactions

Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia.

In post-marketing reports, serious and fatal infusion reactions have been reported. Severe reactions, which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable, including progressive worsening, initial improvement followed by clinical deterioration or delayed post-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to days following a serious infusion reaction.

Interrupt ONTRUZANT infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered (which may include epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen). Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions.

There are no data regarding the most appropriate method of identification of patients who may safely be retreated with trastuzumab products after experiencing a severe infusion reaction. Prior to resumption of trastuzumab infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated trastuzumab infusions, others had recurrent severe infusion reactions despite pre-medications.

Embryo-fetal Toxicity

Trastuzumab products can cause fetal harm when administered to a pregnant woman. In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Verify the pregnancy status of females of reproductive potential prior to the initiation of ONTRUZANT. Advise pregnant women and females of reproductive potential that exposure to ONTRUZANT during pregnancy or within 7 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of ONTRUZANT.

Pulmonary Toxicity

Trastuzumab product use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.

Exacerbation of Chemotherapy-induced Neutropenia

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3 to 4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not.

Drug Interactions

Patients who receive anthracycline after stopping trastuzumab products may be at increased risk of cardiac dysfunction because of trastuzumab’s long washout period based on population PK Analysis. If possible, physicians should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab products. If anthracyclines are used, the patient’s cardiac function should be monitored carefully.

Adverse Reactions

The most common adverse reactions in patients receiving trastuzumab products in the adjuvant and metastatic breast cancer setting are fever, chills, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of trastuzumab product treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity.

In the metastatic gastric cancer setting, the most common adverse reactions (≥ 10%) that were increased (≥ 5% difference) in the patients receiving trastuzumab as compared to patients receiving chemotherapy alone were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. The most common adverse reactions which resulted in discontinuation of trastuzumab treatment in the absence of disease progression were infection, diarrhea, and febrile neutropenia.

Use in Specific Populations

Lactation

There is no information regarding the presence of trastuzumab products in human milk, the effects on the breastfed infant, or the effects on milk production. Published data suggest human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for ONTRUZANT treatment and any potential adverse effects on the breastfed child from ONTRUZANT or from the underlying maternal condition. This consideration should also take into account the trastuzumab product wash out period of 7 months.

Pediatric Use

The safety and effectiveness of trastuzumab products in pediatric patients have not been established.

Geriatric Use

Trastuzumab has been studied in patients who were 65 years of age or over in the adjuvant and metastatic breast cancer treatment settings. The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease, or adjuvant therapy.

Please see Prescribing Information for ONTRUZANT (trastuzumab-dttb) including Boxed Warning about cardiomyopathy, infusion reactions (pulmonary toxicity), and embryo-fetal toxicity at View Source