On May 7, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data from clinical trials of 19 approved and investigational medicines across 21 cancer types, will be presented at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program organised by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), which will be held 29-31 May, 2020 (Press release, Hoffmann-La Roche, MAY 7, 2020, View Source [SID1234557204]). A total of 120 abstracts that include a Roche medicine will be presented at this year’s meeting.

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"At ASCO (Free ASCO Whitepaper), we will present new data from many investigational and approved medicines across our broad oncology portfolio," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "These efforts exemplify our long-standing commitment to improving outcomes for people with cancer, even during these unprecedented times. By integrating our medicines and diagnostics together with advanced insights and novel platforms, Roche is uniquely positioned to deliver the healthcare solutions of the future."

Together with its partners, Roche is pioneering a comprehensive approach to cancer care, combining new diagnostics and treatments with innovative, integrated data and access solutions for approved medicines that will both personalise and transform the outcomes of people affected by this deadly disease.

Key presentations
First results of tiragolumab, Roche’s novel cancer immunotherapy designed to bind to TIGIT, will be shared. These results, from the phase II CITYSCAPE study, examine tiragolumab in combination with Tecentriq (atezolizumab) compared with Tecentriq alone as an initial treatment for people with PD-L1-positive locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC). In addition, updated five-year overall survival rates with Alecensa (alectinib) in people living with treatment-naive anaplastic lymphoma kinase (ALK)-positive metastatic/advanced NSCLC will be presented. With five approved lung cancer medicines and an extensive pipeline across multiple subtypes, Roche’s ultimate aim is to provide an effective treatment option for each person diagnosed with the disease, tailored to the unique characteristics of their tumours.

Studies featured from partnerships with Flatiron Health and Foundation Medicine demonstrate how the use of next-generation sequencing (NGS) may help inform treatment decisions, optimise testing and enable personalised therapy, including an ongoing additional study designed to prospectively link longitudinal, real-world clinical data with genomic, imaging and outcomes data for patients with advanced lung cancers. The study is monitoring circulating tumour DNA (ctDNA) using FoundationOne Liquid, and tumour tissue samples will be genomically profiled using FoundationOne CDx.

Further information on Roche’s contribution to the ASCO (Free ASCO Whitepaper) 2020 scientific programme, as well as the latest innovations and developments in Roche’s approach to accelerating progress in cancer care, will be featured during the Roche virtual analyst event from 5:00 – 6:15 pm CEST on Friday,29 May. Further details are available here

To access Roche’s ASCO (Free ASCO Whitepaper) virtual newsroom, please register via this link: View Source

Follow Roche on Twitter via @Roche and keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO20.

Overview of key presentations featuring Roche medicines at ASCO (Free ASCO Whitepaper) 2020

Medicine Abstract title Abstract number
Lung cancer
Tiragolumab Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE) #9503
Oral abstract session

Alecensa (alectinib) Updated overall survival (OS) and safety data from the randomized, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC #9518
Poster: 284
Poster discussion session
Tecentriq (atezolizumab) Patient-reported outcomes (PROs) in the randomized, phase III IMpower110 study of atezolizumab (atezo) vs chemotherapy in 1L metastatic NSCLC #9594
Poster: 360
Poster session
Tecentriq IMpower150: exploratory analysis of brain metastases development #9587
Poster: 353
Poster session
Tecentriq IMpower150: exploratory efficacy analysis in patients (pts) with bulky disease N/A
e-publication
Flatiron Health data in lung cancer
Real World Data A multi-stakeholder platform to prospectively link longitudinal real-world clinico-genomic, imaging, and outcomes data for patients with metastatic lung cancer #TPS2087
Poster: 79
Poster session
Real World Data Genomic testing among patients (pts) with newly diagnosed advanced non-small cell lung cancer (aNSCLC) in the United States: a contemporary clinical practice patterns study #9592
Poster: 358
Poster session
Solid tumours
Rozlytrek (entrectinib) Updated entrectinib data in children and adolescents with recurrent or refractory solid tumors, including primary CNS tumor #107
Clinical science symposium
Rozlytrek Efficacy and safety of entrectinib in patients (pts) with NTRK-Fusion-Positive (NTRK-fp) solid tumors: An updated integrated analysis #3605
Poster: 335
Poster session
Genitourinary and gastrointestinal cancers
Tecentriq IMvigor010: primary analysis from a phase III randomized study of adjuvant atezolizumab (atezo) versus observation (obs) in high-risk muscle-invasive urothelial carcinoma (MIUC) #5000
Oral abstract session

Tecentriq Tumor, immune, and stromal characteristics associated with clinical outcomes with atezolizumab (atezo) + platinum-based chemotherapy (PBC) or atezo monotherapy (mono) versus PBC in metastatic urothelial cancer (mUC) from the phase III IMvigor130 study #5011
Clinical science symposium
Tecentriq Phase Ib/II open-label, randomized evaluation of 2L atezolizumab + PEGPH20 versus control in MORPHEUS-pancreatic ductal adenocarcinoma (M-PDAC) and MORPHEUS-gastric cancer (M-GC) #4540
Poster: 148
Poster session
Tecentriq, Avastin (bevacizumab) Complete responses (CR) in patients receiving atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (sor) in IMbrave150: a phase III clinical trial for unresectable hepatocellular carcinoma (HCC) #4596
Poster: 204
Poster session
Ipatasertib Circulating tumor DNA (ctDNA) dynamics associate with treatment response and radiological progression-free survival (rPFS): Analyses from a randomized phase II trial in metastatic castration-resistant prostate cancer (mCRPC) #5508
Oral abstract session

Blood cancer
Venclexta (venetoclax)

Impact of premature venetoclax (Ven) discontinuation/interruption on outcomes in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Phase III MURANO study results #8028
Poster: 361
Poster session
Venclexta, Gazyva (obinutuzumab) Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial #8027
Poster: 360
Poster session
Gazyva Comparison of efficacy and safety with obinutuzumab plus chemotherapy versus rituximab plus chemotherapy in patients with previously untreated follicular lymphoma – Updated results from the phase III Gallium Study #8023
Poster: 356
Poster session
Breast cancer
Kadcyla (trastuzumab emtansine), Perjeta (pertuzumab) Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC) #500
Oral abstract session

Kadcyla Biomarker data from KATHERINE: A phase III study of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab (H) in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer #502
Oral abstract session

About Roche in Oncology
Roche has been working to transform cancer care for more than 50 years, bringing the first specifically designed anti-cancer chemotherapy drug, fluorouracil, to patients in 1962. Roche’s commitment to developing innovative medicines and diagnostics for cancers remains steadfast.

The Roche Group’s portfolio of innovative cancer medicines includes: Alecensa (alectinib); Avastin (bevacizumab); Cotellic (cobimetinib); Erivedge (vismodegib); Gazyva/Gazyvaro (obinutuzumab); Herceptin (trastuzumab); Kadcyla (trastuzumab emtansine); MabThera/Rituxan (rituximab); Perjeta (pertuzumab); Polivy (polatuzumab vedotin-piiq); Tarceva (erlotinib); RozlytrekTM (entrectinib); Tecentriq (atezolizumab); Venclexta/Venclyxto (venetoclax); Xeloda (capecitabine); Zelboraf (vemurafenib). Furthermore, the Roche Group has a robust investigational oncology pipeline focusing on new therapeutic targets and novel combination strategies. For more information on Roche’s approach to cancer, visit www.roche.com.

About Roche in Personalised Healthcare
For more than 20 years, Roche has helped lay the scientific groundwork for personalised healthcare with treatments that target the underlying biology of cancer and other diseases. Now, with profound changes in data and technology transforming how medicines are discovered, developed and delivered to patients, we are uniquely positioned to extend this approach across all of healthcare. With our ability to integrate research and development, personalised diagnosis, disease monitoring and treatment access, we are advancing personalised healthcare for every aspect of the patient experience.

Our strategy is rooted in groundbreaking science that can accelerate drug discovery and development. We are also leveraging technologies such as real-world datasets, artificial intelligence, genomic profiling and digital health across our therapeutic portfolio, with an initial emphasis on oncology, neurology, ophthalmology and diagnostics. Through collaborations with academic institutions, industry partners, patients, physicians and regulatory agencies, our goal is to dramatically improve the performance of the entire healthcare ecosystem and the lives of every patient.

On May 7, 2020 VBL Therapeutics (Nasdaq: VBLT), reported that it has entered into definitive agreements with several institutional investors for the purchase and sale of 6,349,208 ordinary shares of the Company, at a purchase price of $1.575 per share, in a registered direct offering priced at-the-market under Nasdaq rules (Press release, VBL Therapeutics, MAY 7, 2020, View Source [SID1234557203]). VBL has also agreed to issue to the investors, in a concurrent private placement, unregistered warrants to purchase up to an aggregate of 6,349,208 of VBL’s ordinary shares. The warrants have an exercise price of $1.45 per ordinary share, will be immediately exercisable and will expire 18 months from the date of issuance.

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The closing of the offering is expected to occur on or about May 11, 2020, subject to the satisfaction of customary closing conditions.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds from this offering are expected to be approximately $10.0 million, before deducting the placement agent’s fees and other estimated offering expenses. The Company intends to use the net proceeds from this offering for working capital and general corporate purposes.

The ordinary shares (but not the warrants or the ordinary shares underlying the warrants) are being offered by VBL pursuant to a "shelf" registration statement on Form F-3 (File No. 333-222138) previously filed with the Securities and Exchange Commission (the "SEC") on December 18, 2017 and declared effective by the SEC on January 4, 2018. The offering of the ordinary shares will be made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the ordinary shares being offered will be filed with the SEC. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (646) 975-6996 or e-mail at [email protected].

The warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the ordinary shares underlying the warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the warrants and underlying ordinary shares may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws.

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

On May 7, 2020 Mediolanum Farmaceutici Spa, a leading Italian pharmaceutical Group operating on the international scene, focused on research, development, production and distribution of innovative and original medicines to improve patients’ health and quality of life, reported that it has acquired the French company ElsaLys Biotech (Press release, Mediolanum Farmaceutici, MAY 7, 2020, View Source [SID1234557197]).

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ElsaLys Biotech is a clinical stage immuno-oncology company that designs and develops a new generation of therapeutic antibodies that target tumours and their immune and vascular microenvironment.

By modulating the action of immune cells (immunomodulator antibodies) or by blocking the mechanisms that promote tumour growth (targeted antibodies), ElsaLys Biotech intends to offer novel treatment solutions to patients, with a particular focus on whom the current therapies are less or no longer beneficial. The Company relies on a strong academic network of international standing, and an R&D platform that covers the clinical development and the commercialization of immune-based therapies.

Thanks to this acquisition, Mediolanum Farmaceutici will further consolidate its presence on the international markets, directly or through partnerships.

"In addition to its proven expertise in the Cardiovascular area, Mediolanum Farmaceutici is renowned for its broad portfolio in Oncology, providing clinicians and patients with innovative high-quality therapeutic solutions to transform the lives of people affected by cancer – stated Alessandro Del Bono, CEO of Mediolanum Farmaceutici Group. The acquisition of ElsaLys Biotech’s pipeline represents a significant step forward in our international expansion, while increasing the Group’s R&D capabilities".

"The acquisition of ElsaLys Biotech by Mediolanum Farmaceutici Group is a great opportunity for our company" – added Christine Guillen, CEO and co-founder of ElsaLys Biotech. We are proud to join the Mediolanum family who has a huge experience in the marketing of pharmaceuticals and a well-known innovation strategy".

ElsaLys Biotech has three R&D proprietary development programs, including Inolimomab (LEUKOTAC), an immunotherapy monoclonal antibody that targets the interleukin-2 receptor (IL-2), a chemical molecule named cytokine that contributes to the development and proliferation of some white blood cells including T-cells responsible for steroid-refractory acute Graft-versus-Host Disease (aGvHD), a rare life-threatening disease that can occur after allogeneic stem cell transplantation.

Furthermore, ElsaLys Biotech is currently developing anti-CD160 antibody variants to achieve several therapeutic goals, both as monotherapy and in combination with existing treatments.

ELB011 is an anti-CD160 antibody that via its dual anti-angiogenic and anti-inflammatory properties will bring a novel option to treat vascular eye diseases, in particular Age-related Macular Degeneration (AMD) and diabetic retinopathy.

ELB021 is an anti-CD160 antibody (endowed with both anti-angiogenic and immuno-modulator properties) aimed at blocking newly formed blood vessels and reactivating anti-tumour immune response, through an alternative and complementary pathway to anti-PD1 (immune checkpoint inhibitor widely used in the clinic).

On May 7, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it has submitted a supplemental New Drug Application (sNDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for trastuzumab deruxtecan (DS-8201), a HER2 directed antibody drug conjugate (ADC), for the treatment of patients with HER2 positive metastatic gastric cancer (Press release, Daiichi Sankyo, MAY 7, 2020, View Source [SID1234557194]).

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Trastuzumab deruxtecan has previously received SAKIGAKE designation for this second potential indication and will receive an expedited review time of six months. Currently, there are no HER2 directed treatment options approved for patients with HER2 positive metastatic gastric cancer who have progressed after trastuzumab.

"Today’s submission by Daiichi Sankyo brings us closer to bringing trastuzumab deruxtecan to a population of patients with unmet medical need in Japan," said Wataru Takasaki, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo. "If approved, trastuzumab deruxtecan has the potential to meaningfully advance the treatment of patients with HER2 positive metastatic gastric cancer as the first ever antibody drug conjugate approved to treat this type of cancer."

The Japan sNDA is based on data from the pivotal phase 2 DESTINY-Gastric01 trial and phase 1 trial published in The Lancet Oncology. In DESTINY-Gastric01, patients treated with trastuzumab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR) as assessed by an independent review committee as well as in overall survival (OS) compared to patients treated with investigator’s choice of chemotherapy (irinotecan or paclitaxel monotherapy). The full results of DESTINY-Gastric01 will be presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

The overall safety and tolerability profile of trastuzumab deruxtecan in DESTINY-Gastric01 was consistent with that seen in the phase 1 trial in which the most common adverse events (≥30 percent, any grade) were hematologic and gastrointestinal including neutrophil count decrease, anemia, nausea and decreased appetite. There were cases of drug-related interstitial lung disease (ILD) and pneumonitis, the majority of which were grade 1 and 2 with two grade 3 and one grade 4. No ILD-related deaths (grade 5) occurred in patients with gastric cancer in the phase 1 trial or in the DESTINY-Gastric01 trial.

Accelerated approval in the U.S. and approval in Japan under the conditional early approval system were recently received for trastuzumab deruxtecan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens.

About HER2

HER2 is a cell growth-promoting tyrosine kinase receptor protein expressed on the surface of many types of tumors including gastric, breast and lung cancers. HER2 overexpression is associated with a specific HER2 gene alteration known as HER2 amplification and is often associated aggressive disease and poorer prognosis.[1]

About Gastric Cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality; there were approximately one million new cases reported in 2018 and 783,000 deaths.[2] Incidence rates for gastric cancer are markedly higher in eastern Asia, where approximately half of all cases occur.8 South Korea and Japan have the first and third highest incidence rates of gastric cancer worldwide, respectively; in 2018, the age-standardized rate in Japan was 27.5 per 100,000 and in South Korea it was 39.6 per 100,000.[3]

Approximately one in five gastric cancers are HER2 positive.[4] Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease the survival rate remains modest.[5] Recommended first-line treatment for HER2 positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve outcomes when added to chemotherapy.[6] For gastric cancer that progresses on first line treatment, trastuzumab has not shown any further benefit and there are no other approved HER2 targeting medicines.6

About DESTINY-Gastric01

DESTINY-Gastric01 is a pivotal phase 2, open-label, multi-center study assessing the safety and efficacy of trastuzumab deruxtecan in 189 patients from Japan and South Korea with HER2 expressing advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two or more prior regimens including fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab. Patients were randomized 2:1 to receive trastuzumab deruxtecan or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with trastuzumab deruxtecan 6.4 mg/kg once every three weeks or chemotherapy given on the same schedule. The primary endpoint of the study is ORR. Secondary endpoints include OS, progression-free survival, duration of response, disease control rate and time to treatment failure.

About Trastuzumab Deruxtecan

Trastuzumab deruxtecan (formerly known as DS-8201; trastuzumab deruxtecan outside the U.S.; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC Scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is comprised of a HER2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker.

Trastuzumab deruxtecan has not been approved in the EU, or countries outside of Japan and the United States, for any indication. It is an investigational agent globally for various indications. Safety and effectiveness have not been established for the subject proposed use.

About the Trastuzumab Deruxtecan Clinical Development Program

A comprehensive development program for trastuzumab deruxtecan is underway globally with six pivotal trials evaluating the efficacy and safety of trastuzumab deruxtecan monotherapy across multiple HER2 driven cancers including breast, gastric, colorectal and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

About the Collaboration between Daiichi Sankyo and AstraZeneca

In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for the manufacturing and supply.

U.S. FDA-Approved Indication for ENHERTU

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

●　Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.

●　Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Contraindications

WARNINGS AND PRECAUTIONS
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg prednisolone or equivalent). Upon improvement, follow by gradual taper (e.g., 4 weeks).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, a decrease in neutrophil count was reported in 30% of patients and 16% had Grade 3 or 4 events. Median time to first onset was 1.4 months (range: 0.3 to 18.2). Febrile neutropenia was reported in 1.7% of patients.

Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. Permanently discontinue ENHERTU if LVEF of <40% or absolute decrease from baseline of >20% is confirmed. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Adverse Reactions
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common adverse reactions (frequency ≥20%) were nausea (79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation (35%), decreased appetite (32%), anemia (31%), neutropenia (29%), diarrhea (29%), leukopenia (22%), cough (20%), and thrombocytopenia (20%).

Use in Specific Populations

●　Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.

●　Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.

●　Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.

●　Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.

●　Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%).

●　Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

On May 6, 2020 BridgeBio Pharma, Inc. (Nasdaq: BBIO) reported that it will present at the Bank of America Securities 2020 Health Care Conference on Thursday, May 14, 2020 at 11 AM (ET) (Press release, BridgeBio, MAY 6, 2020, View Source [SID1234576230]).

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The presentation will be webcast live and can be accessed at www.bridgebio.com on the For Investors page under News & Events. The webcast will be available for replay through August 12, 2020.