On October 19, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported updates on its advancing pipeline of chimeric antigen receptor (CAR) and T cell receptor (TCR) product candidates and KTE-C19 launch readiness at its Investor Day in New York on October 18, 2016 (Press release, Kite Pharma, OCT 19, 2016, View Source [SID1234515917]). Schedule your 30 min Free 1stOncology Demo! "At Kite, our goal is to cure cancer. With KTE-C19, we may have the opportunity to transform the treatment of aggressive non-Hodgkin lymphoma (NHL)," said Arie Belldegrun, M.D., FACS, Chairman, President and Chief Executive Officer of Kite. "While we prepare to manufacture and commercialize KTE-C19 upon approval, we believe this is just the beginning. The breadth of the pipeline we unveiled today, combined with our innovative T cells 2.0 programming, has the potential to deliver hope for a cure to thousands of people across 15 hematological and solid cancer indications."
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Kite detailed four new near-term clinical development programs, including timelines for planned Investigational New Drug (IND) applications:
KITE-796: IND in 2018
Directed against the most promising target for acute myeloid leukemia (AML)
single-chain variable fragment (scFv) from human anti-CLL-1 monoclonal antibody (mAb) to minimize immunogenicity
"Control CAR" to incorporate dynamic switch technology
First Kite product candidate from Amgen collaboration
KITE-585: IND in 2017
Directed against the best and a validated target for multiple myeloma (MM)
scFv from human anti-BCMA mAb to minimize immunogenicity
Will leverage Kite’s clinical development and manufacturing expertise for program acceleration
KITE-718: IND in 2016
Directed against next generation MAGE A3/A6, a cancer testis antigen and validated target for TCR therapy for non-small cell lung cancer and bladder cancer
Built on National Cancer Institute (NCI) proof of concept with improved T cell manufacturing technologies
KITE-439: IND in 2018
Directed against HPV-16 E7, a viral oncoprotein target for TCR therapy for cervical cancer and head and neck cancer
Internal expertise to select best-in-class TCR candidates without affinity enhancement
T cells 2.0 next generation cell programming is in development to design engineered T cells that increase safety, potency and effectiveness:
Safety: Dynamic control switch technology ("Control CAR") that may regulate and allow the ability to dial up and dial down engineered T-cell expansion
Potency: Transmembrane Immunomodulatory Proteins (TIPs) for solid tumors that may function at the immune synapse thereby limiting immune-activation to engineered T cells
Effectiveness: T-cell differentiation technology that may enable a reliable and renewable cell source to advance the clinical application of universal allogeneic T-cell therapy
Kite is advancing its KTE-C19 pipeline with ongoing and expanded ZUMA studies to evaluate six additional indications:
ZUMA-2: Mantle cell lymphoma (MCL), with initial Phase 2 data expected in 2017
ZUMA-3: Adult acute lymphoblastic leukemia (Adult ALL), with initial Phase 1 data expected in 2016
ZUMA-4: Pediatric acute lymphoblastic leukemia (Pediatric ALL), with initial Phase 1 data expected in 2016
ZUMA-5: Indolent NHL, with first patient enrolled expected in the first quarter of 2017
ZUMA-7: 2nd line DLBCL, with first patient enrolled expected in 2017
ZUMA-8: Chronic lymphocytic leukemia (CLL), with first patient enrolled expected in 2017
Kite reviewed its proven clinical cell manufacturing capability, preparations to produce and deliver KTE-C19 at commercial scale following U.S. regulatory approval, and ongoing activities to automate next generation manufacturing:
Efficient and consistent manufacturing process
High clinical manufacturing success rate – 99 percent manufacturing of KTE-C19 for patients enrolled in ZUMA-1
Estimated capacity for 4,000+ patient treatments per year and ability to expand quickly
Next generation automation planned to enter feasibility testing in 2017 through collaboration with GE Research
Kite discussed its ongoing activities to build scientific awareness and to commercialize KTE-C19 following U.S. regulatory approval:
Early market research substantiates awareness of CAR-T therapy and potential for adoption
Medical Science Liaison team ready for deployment in the fourth quarter of 2016
Proactive Market Access strategy and engagement with payers
Controlled launch approach lays groundwork for expansion, understanding of therapy, patient management, and reimbursement
A replay of the audio webcast will be available for approximately 30 days and can be accessed through the Events and Presentations section under the Investors tab of Kite’s website at www.kitepharma.com.
About KTE-C19
Kite Pharma’s lead product candidate, KTE-C19, is an investigational therapy in which a patient’s T cells are engineered to express a CAR to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.
FDA Approves Lilly’s LARTRUVO™ (olaratumab) in Combination with Doxorubicin for Soft Tissue Sarcoma
On October 19, 2016 Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) has granted approval of LARTRUVO (olaratumab injection, 10 mg/mL), in combination with doxorubicin, for the treatment of adults with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery (Press release, Eli Lilly, OCT 19, 2016, View Source [SID1234515915]). LARTRUVO’s indication is approved under Accelerated Approval, and is based on data from the Phase 2 portion of the pivotal JGDG trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. LARTRUVO, in combination with doxorubicin, is the first FDA-approved front-line therapy for STS in four decades. The confirmatory Phase 3 trial, ANNOUNCE, is fully enrolled. Schedule your 30 min Free 1stOncology Demo! "LARTRUVO represents an important step forward in soft tissue sarcoma treatment," said William D. Tap, M.D., chief of the sarcoma medical oncology services at Memorial Sloan Kettering Cancer Center in New York and the principal investigator of the JGDG registration trial. "We are pleased with this approval, which will provide patients with a treatment option that offers new hope in their battle against this difficult disease."
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Soft tissue sarcoma is a complex disease with multiple subtypes, making it hard to diagnose and difficult to treat. For decades, there have been no first-line therapeutic advancements for STS that have improved overall survival (OS). According to the American Cancer Society, in 2015, there were an estimated 12,000 new STS cases diagnosed and nearly 5,000 deaths in the U.S. alone, representing an unmet medical need.
LARTRUVO is the first monoclonal antibody approved to treat STS. It also received Fast Track, Orphan Drug and Breakthrough Therapy designations from the FDA for this indication, and was reviewed and approved under the FDA’s Accelerated Approval program. This program allows for earlier approval of drugs that treat serious conditions and that fill an unmet medical need.
"The approval of LARTRUVO is based on an encouraging and positive study for patients, and represents progress in soft tissue sarcoma treatment. For the first time in four decades, we now have a combination regimen – LARTRUVO and doxorubicin – that offers progress over doxorubicin alone in the front-line setting, by improving overall survival for people with soft tissue sarcoma," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "This continues our commitment to discovering new ways to treat cancer, including for people who have rare types of cancer."
"The entire sarcoma patient community is excited to have an innovative medicine approved for the treatment of advanced soft tissue sarcoma," said Bert E. Thomas IV, PhD, MBA, CEO of the Sarcoma Foundation of America. "We are confident that the approval of LARTRUVO may help these patients live longer."
The approval of LARTRUVO is based on the results of JGDG, an open-label, randomized, active-controlled study of 133 patients, which compared LARTRUVO, in combination with doxorubicin chemotherapy, to doxorubicin alone in patients with STS with a histologic subtype for which an anthracycline-containing regimen was appropriate and which is not amenable to curative treatment with surgery or radiotherapy. The efficacy outcome measures were OS, progression-free survival (PFS), and objective response rate (ORR).
Median OS was improved by 11.8 months in patients randomized to receive LARTRUVO plus doxorubicin compared to patients randomized to doxorubicin alone, and was statistically significant. Median OS was 26.5 months (95% CI: 20.9, 31.7) on the LARTRUVO-doxorubicin arm compared to 14.7 months (95% CI: 9.2, 17.1) on the doxorubicin-only arm (stratified hazard ratio [HR], 0.52; 95% CI: 0.34, 0.79, < 0.05). The study met its prespecified protocol-defined endpoint for PFS. Patients treated on the LARTRUVO and doxorubicin arm achieved 8.2 months (95% CI: 5.5, 9.8) of median PFS compared to 4.4 months (95% CI: 3.1, 7.4) on the doxorubicin-only arm (stratified hazard ratio [HR], 0.74; 95% CI: 0.46, 1.19), based on independent review. The number of events at the time of analysis was 37 (56%) on the LARTRUVO-doxorubicin arm and 34 (51%) on the doxorubicin-only arm. The number of deaths at the time of analysis was 39 (59%) on the LARTRUVO-doxorubicin arm and 52 (78%) on the doxorubicin-only arm. Objective response rate (ORR), based on independent review and defined as complete response (CR) plus partial response (PR), was also assessed with an ORR of 18.2 percent (95% CI: 9.8, 29.6) (CR, 4.5%; PR, 13.6%) on the LARTRUVO-doxorubicin arm and 7.5 percent (95% CI: 2.5, 16.6) (CR, 1.5%; PR, 6%) on the doxorubicin-only arm.
The labeling for LARTRUVO contains Warnings and Precautions for infusion-related reactions and embryo-fetal toxicity. The most commonly reported adverse reactions (all grades) occurring in ≥20 percent of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were nausea (73% vs 52%), fatigue (69% vs 69%), musculoskeletal pain (64% vs 25%), mucositis (53% vs 35%), vomiting (45% vs 19%), diarrhea (34% vs 23%) and headache (20% vs 9%). The most common laboratory abnormalities (all grades) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%), neutropenia (65% vs 63%), thrombocytopenia (63% vs 44%), hyperglycemia (52% vs 28%), elevated aPTT (33% vs 13%), hypokalemia (21% vs 15%) and hypophosphatemia (21% vs 7%). Febrile neutropenia was reported in 13% of LARTRUVO plus doxorubicin-treated patients versus 12% of doxorubicin-treated patients.
Adverse reactions resulting in permanent discontinuation of LARTRUVO occurred in 8% (5/64) of patients. The most common adverse reaction leading to LARTRUVO discontinuation was infusion-related reaction (3%). Dose reductions of LARTRUVO for adverse reactions occurred in 25% (16/64) of patients; the most common adverse reaction leading to dose reduction was Grade 3 or 4 neutropenia (20%). Dose delays of LARTRUVO for adverse reactions occurred in 52% (33/64) of patients; the most common adverse reactions resulting in dose delays were neutropenia (33%), thrombocytopenia (8%) and anemia (5%). See the full Important Safety Information at the end of this press release and the Prescribing Information.
Lilly is committed to helping patients access LARTRUVO and offers support programs for qualified uninsured, underinsured and insured patients who receive LARTRUVO for its FDA-approved indication and who may need assistance with their out-of-pocket prescription medication costs, including a co-pay program where qualified patients pay no more than $25 per infusion. Patients and healthcare professionals with questions about LARTRUVO should contact The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979) or visit www.lilly.com.
About LARTRUVO (olaratumab)
LARTRUVO is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody that specifically binds PDGFR-α and prevents receptor activation. LARTRUVO exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupted the PDGFR-α signaling pathway in in vivo tumor implant models. Information about additional clinical trials for LARTRUVO in sarcoma can be found at ClinicalTrials.gov (in the search box on the home page, type in "olaratumab").
A Phase 3 trial of LARTRUVO and doxorubicin in advanced STS is fully enrolled (ClinicalTrials.gov Identifier: NCT02451943).
About the JGDG Trial
JGDG was an open-label, randomized, active-controlled study that compared LARTRUVO, in combination with doxorubicin chemotherapy, to doxorubicin alone in patients with unresectable, soft tissue sarcoma (STS).
The study enrolled 133 doxorubicin-naïve patients with STS with a histologic subtype for which an anthracycline-containing regimen was appropriate and which is not amenable to curative treatment with surgery or radiotherapy. Sixty-six patients with an ECOG performance status of 0 – 2 were randomized to the LARTRUVO-doxorubicin arm and 67 to the doxorubicin-only arm.
Patients were randomized to receive LARTRUVO at 15 mg/kg as an intravenous infusion on day one of each 21-day cycle in combination with 75 mg/m2 doxorubicin, and LARTRUVO only on day eight. Doxorubicin was administered following LARTRUVO infusion on day one of each 21-day cycle for up to eight cycles. After doxorubicin was discontinued, patients on the LARTRUVO plus doxorubicin arm without evidence of disease progression or unacceptable toxicity could continue to receive LARTRUVO monotherapy until disease progression. All patients received the cardioprotectant dexrazoxane prior to doxorubicin in cycles five to eight.
About Sarcomas
Sarcomas are a diverse and relatively rare type of cancer that usually develop in the connective tissue of the body, which include fat, blood vessels, nerves, bones, muscles, deep skin tissues and cartilage. Soft tissue sarcoma is a complex disease with multiple subtypes, making it very hard to diagnose and difficult to treat. For decades, there have been no front-line therapeutic advancements for STS that have improved overall survival. According to the American Cancer Society, in 2015, there were an estimated 12,000 new STS cases diagnosed and nearly 5,000 deaths in the U.S. alone.
INDICATION
LARTRUVO is indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.
This indication is approved under Accelerated Approval. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
IMPORTANT SAFETY INFORMATION FOR LARTRUVO
Warnings and Precautions
Infusion-Related Reactions
Infusion-related reactions (IRR) occurred in 70 (14%) of 485 patients who received at least one dose of LARTRUVO across clinical trials. For 68 of these 70 patients (97%), the first occurrence of IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11 (2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR included flushing, shortness of breath, bronchospasm, or fever/chills, and in severe cases symptoms manifested as severe hypotension, anaphylactic shock, or cardiac arrest. Infusion-related reactions required permanent discontinuation in 2.3% of patients and interruption of infusion in 10% of patients. All 59 patients with Grade 1 or 2 IRR resumed LARTRUVO; 12 (20%) of these patients had a Grade 1 or 2 IRR with rechallenge. The incidence of IRR in the overall safety database (N = 485) was similar (18% versus 12%) between those who did (56%) and those who did not (44%) receive premedication. Monitor patients during and following LARTRUVO infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Immediately and permanently discontinue LARTRUVO for Grade 3 or 4 IRR.
Embryo-Fetal Toxicity
Based on animal data and its mechanism of action, LARTRUVO can cause fetal harm when administered to a pregnant woman. Animal knockout models link disruption of platelet-derived growth factor receptor alpha (PDGFR-α) signaling to adverse effects on embryo-fetal development. Administration of an anti-murine PDGFR-α antibody to pregnant mice during organogenesis caused malformations and skeletal variations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LARTRUVO and for 3 months after the last dose.
Most Common Adverse Reactions/Lab Abnormalities
The most commonly reported adverse reactions (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were nausea (73% vs 52%; 2% vs 3%), fatigue (69% vs 69%; 9% vs 3%), musculoskeletal pain (64% vs 25%; 8% vs 2%), mucositis (53% vs 35%; 3% vs 5%), alopecia (52% vs 40%; 0% vs 0%), vomiting (45% vs 19%; 0% vs 0%), diarrhea (34% vs 23%; 3% vs 0%) decreased appetite (31% vs 20%; 2% vs 0%), abdominal pain (23% vs 14%; 3% vs 0%), neuropathy (22% vs 11%; 0% vs 0%), and headache (20% vs 9%; 0% vs 0%).
The most common laboratory abnormalities (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%; 44% vs 37%), neutropenia (65% vs 63%; 48% vs 38%) and thrombocytopenia (63% vs 44%; 6% vs 11%), hyperglycemia (52% vs 28%; 2% vs 3%), elevated aPTT (33% vs 13%; 5% vs 0%), hypokalemia (21% vs 15%; 8% vs 3%), and hypophosphatemia (21% vs 7%; 5% vs 3%).
Use in Specific Populations
Lactation: Because of the potential risk for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with LARTRUVO and for at least 3 months following the last dose.
For more information about LARTRUVO, please see full Prescribing Information at View Source
FDA approves Roche’s cancer immunotherapy TECENTRIQ (atezolizumab) for people with a specific type of metastatic lung cancer
On October 19, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) approved TECENTRIQ (atezolizumab) for the treatment of people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK gene abnormalities (Press release, Hoffmann-La Roche , OCT 19, 2016, View Source [SID1234515914]). This approval is based on results from the randomised Phase III OAK and Phase II POPLAR studies. The largest study, OAK, showed that TECENTRIQ helped people in the overall study population live a median of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.74, 95% CI: 0.63, 0.87). The study enrolled people regardless of their PD-L1 status and included both squamous and non-squamous disease types. Schedule your 30 min Free 1stOncology Demo! "TECENTRIQ is a new option to help people with this type of previously treated metastatic lung cancer, regardless of PD-L1 expression, live longer than chemotherapy" said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "TECENTRIQ is the first and only approved cancer immunotherapy designed to target the PD-L1 protein, which may play an important role in the way the medicine works."
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The TECENTRIQ development programme includes more than 15 clinical trials in lung cancer, including seven phase III studies in previously untreated (first-line) lung cancer. These studies are evaluating the use of TECENTRIQ alone or in combination with other medicines.
About the OAK study
OAK is a global, multicentre, open-label, randomised, controlled Phase III study that evaluated the efficacy and safety of TECENTRIQ compared with docetaxel in 1,225 people with locally advanced or metastatic NSCLC whose disease had progressed following previous treatment with platinum-containing chemotherapy, with the primary analysis consisting of the first 850 randomised patients. Patients with both squamous and non-squamous disease were randomised (1:1) to receive either TECENTRIQ administered intravenously at 1200 mg every 3 weeks or docetaxel administered intravenously at 75 mg/m2 every 3 weeks. The co-primary endpoints were overall survival (OS) in all randomised patients (ITT population) and in a PD-L1-selected subgroup in the primary analysis population.
About the POPLAR study
POPLAR is a multicentre, open-label, randomised, Phase II study evaluating the efficacy and safety of TECENTRIQ compared with chemotherapy (docetaxel) in people with previously treated recurrent locally advanced or metastatic NSCLC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety.
A summary of the efficacy data from the OAK and POPLAR studies that supports this approval is included below.
The most common side effects (≥ 20%) in patients with metastatic non-small cell lung cancer were fatigue, decreased appetite, dyspnea (shortness of breath), cough, nausea, musculoskeletal pain, and constipation. Nine patients (6.3%) who were treated with TECENTRIQ experienced either pulmonary embolism (2), pneumonia (lung infection) (2), pneumothorax, ulcer hemorrhage (bleeding ulcer), cachexia secondary to dysphagia, myocardial infarction (heart attack), or large intestinal perforation which led to death. TECENTRIQ was discontinued for adverse reactions in 4 percent (6) of the 142 patients.
About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.
About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, TECENTRIQ may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. TECENTRIQ is currently only approved in the US.
About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.
About personalised cancer immunotherapy (PCI)
The aim of personalised cancer immunotherapy (PCI) is to provide patients and physicians with treatment options tailored to the specific immune biology associated with a person’s individual tumour. The purpose is to inform treatment strategies which provide the greatest number of people with a chance for transformative benefit. In the case of TECENTRIQ, the goal of PD-L1 as a biomarker is to explore PD-L1 expression on tumour cells and tumour infiltrating immune cells and how that correlates with clinical benefit either as a monotherapy or in combination, and across a broad range of tumour types. The Roche PCI research and development programme comprises more than 20 investigational candidates, ten of which are in clinical trials.
PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare. To learn more about the Roche approach to cancer immunotherapy please follow this link:
View Source
Sirenas and Calibr to Form Drug Discovery Collaboration
On October 18, 2016 Sirenas, LLC and the California Institute for Biomedical Research (Calibr) reported that they are collaborating in an effort to discover and develop small molecules in oncology, neuroscience, regenerative medicine and neglected disease (Press release, Sirenas, OCT 18, 2016, View Source [SID1234517478]). Sirenas will provide Calibr with access to its marine-derived chemical diversity, AtlantisTM data mining technology, and synthetic chemistry expertise. Calibr will evaluate compounds in a series of novel biological assays and preclinical disease models.
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"Sirenas has combined the rich chemical diversity found in marine organisms with enabling analytics and informatics to create a powerful platform that we believe could be valuable in targeting some of the most intractable disease phenotypes," said Pete Schultz, President and CEO of Calibr. "We are delighted to pair the tools and expertise we have developed at Calibr with Sirenas’ technology to tackle unmet public health needs."
"Marine organisms have evolved over hundreds of millions of years in highly competitive environments, which has allowed them to evolve very diverse, potent chemistry," said Eduardo Esquenazi, Ph.D., founder and CEO of Sirenas. "In the past, the challenges of identifying and translating those compounds has hindered their pursuit, but we have focused on building an approach that can quickly and cost effectively bring forth these novel compounds into new avenues of drug discovery research. The collaboration with Calibr provides significant biological capabilities to better understand how our compounds work against a number of disease targets."
Financial terms of the collaboration were not disclosed, but the parties plan to co-develop promising leads through definitive preclinical and early clinical studies.
Takeda Showcases Continued Commitment in Hodgkin Lymphoma During 10th International Symposium on Hodgkin Lymphoma (ISHL)
On October 18, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that it will present data on ADCETRIS (brentuximab vedotin) in Hodgkin lymphoma at the 10th International Symposium on Hodgkin Lymphoma (ISHL), October 22 – 25, 2016 in Cologne, Germany. Four studies on brentuximab vedotin will be presented by Takeda during the meeting (Press release, Takeda, OCT 18, 2016, View Source [SID1234515902]). Takeda is the Jubilee sponsor of the 2016 congress.
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"The data to be presented at this year’s ISHL are a proof point of the excellent progress we have made
in furthering the clinical program of brentuximab vedotin," said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. "Through our robust ongoing clinical investigation program, we have continued to see benefit of brentuximab vedotin, particularly in patients with Hodgkin lymphoma or other CD30-positive malignancies who would typically face a poor prognosis. We remain committed to bringing this important therapy to all patients who might benefit from it."
Presentations will highlight scientific updates on brentuximab vedotin in patients with Hodgkin lymphoma. Notably, a presentation highlighting data from the Phase 4 study in patients with relapsed or refractory Hodgkin lymphoma who are ineligible for stem cell transplantation or multi-agent chemotherapy will be presented for the first time. In addition, three presentations will highlight real-world evidence of brentuximab vedotin. The following abstracts were accepted for poster presentations:
Single-arm study of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma (RRHL) who are ineligible for stem cell transplantation (SCT) or multi-agent chemotherapy.
Real-World Effectiveness of Brentuximab Vedotin (BV) vs. Other Treatments in Patients with Relapsed/Refractory Hodgkin Lymphoma (RRHL) Post Autologous Stem-Cell Transplantation (ASCT).
Brentuximab vedotin (BV) in Patients who are Ineligible for Autologous Stem Cell Transplant (ASCT) with Relapsed or Refractory Hodgkin Lymphoma (rrHL): A UK and Germany Retrospective Study.
Risk Factors (RFs) for Relapse in Patients with Relapsed or Refractory Hodgkin Lymphoma (rrHL) after Autologous Stem Cell Transplant (ASCT): A Real-World Analysis in Germany and the United Kingdom (UK).
For more information, the ISHL program is available here: View Source
About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.
About ADCETRIS
ADCETRIS (brentuximab vedotin) is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing proprietary technology by Seattle Genetics. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.
ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). In January 2016, the European Commission approved a Type II variation to include data on the retreatment of adult patients with Hodgkin lymphoma or sALCL who previously responded to ADCETRIS and who later relapse. In June 2016, the European Commission extended the current conditional approval of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT. ADCETRIS has received marketing authorization by regulatory authorities in 65 countries. See important safety information below.
ADCETRIS is being evaluated broadly in more than 45 ongoing clinical trials, including the Phase 3 ALCANZA trial in CD30-positive cutaneous T cell lymphoma (CTCL) and two additional Phase 3 studies, one in frontline classical Hodgkin lymphoma (ECHELON-1) and one in frontline CD30-positive mature T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.
About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and central nervous system therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as our presence in Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit View Source
Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Oncology, the brand for the global oncology business unit of Takeda Pharmaceutical Company Limited, is available through its website, www.takedaoncology.com.
ADCETRIS (brentuximab vedotin) Global Important Safety Information
Active Ingredient: brentuximab vedotin
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
INDICATIONS
ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL):
1. following autologous stem cell transplant (ASCT) or
2. following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option.
ADCETRIS is indicated for the treatment of adult patients with CD30+ HL at increased risk of relapse or progression following ASCT.
ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. In addition, combined use of ADCETRIS with bleomycin is contraindicated as it causes pulmonary toxicity.
SPECIAL WARNINGS & PRECAUTIONS
Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in PML and death can occur in patients treated with ADCETRIS. PML has been reported in patients who received ADCETRIS after receiving multiple prior chemotherapy regimens.
Patients should be closely monitored for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain, and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. ADCETRIS dosing should be held for any suspected case of PML and should be permanently discontinued if a diagnosis of PML is confirmed.
Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. ADCETRIS should be held for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.
Pulmonary Toxicity: Cases of pulmonary toxicity, some with fatal outcomes, have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. New or worsening pulmonary symptoms should be promptly evaluated and treated appropriately.
Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Patients should be carefully monitored during treatment for emergence of possible serious and opportunistic infections.
Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have occurred with ADCETRIS. Patients should be carefully monitored during and after an infusion. If anaphylaxis occurs, administration of ADCETRIS should be immediately and permanently discontinued and appropriate medical therapy should be administered. If an IRR occurs, the infusion should be interrupted and appropriate medical management instituted. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. IRRs are more frequent and more severe in patients with antibodies to ADCETRIS.
Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS. These patients should be monitored closely and managed according to best medical practice.
Peripheral neuropathy (PN): ADCETRIS treatment may cause PN, both sensory and motor. ADCETRIS-induced PN is typically cumulative and reversible in most cases. Patients should be monitored for symptoms of PN, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay and a dose reduction or discontinuation of ADCETRIS.
Hematological toxicities: Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (equal to or greater than one week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose.
Febrile neutropenia: Febrile neutropenia has been reported. Patients should be monitored closely for fever and managed according to best medical practice if febrile neutropenia develops.
Stevens-Johnson syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have been reported. If SJS or TEN occurs, treatment with ADCETRIS should be discontinued and appropriate medical therapy should be administered.
Gastrointestinal (GI) Complications: GI complications, some with fatal outcomes, including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, have been reported. New or worsening GI symptoms should be promptly evaluated and treated appropriately.
Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Liver function should be tested prior to treatment initiation and routinely monitored in patients receiving ADCETRIS. Patients experiencing hepatotoxicity may require a delay, dose modification, or discontinuation of ADCETRIS.
Hyperglycemia: Hyperglycemia has been reported during trials in patients with an elevated body mass index (BMI) with or without a history of diabetes mellitus. However, any patient who experiences an event of hyperglycemia should have their serum glucose closely monitored. Anti-diabetic treatment should be administered as appropriate.
Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations. The recommended starting dose in patients with hepatic impairment or severe renal impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with renal or hepatic impairment should be closely monitored for adverse events.
Sodium content in excipients: This medicinal product contains a maximum of 2.1 mmol (or 47 mg) of sodium per dose. To be taken into consideration for patients on a controlled sodium diet.
INTERACTIONS
Patients who are receiving a strong CYP3A4 and P-gp inhibitor, concomitantly with ADCETRIS may have an increased risk of neutropenia and should be closely monitored. Co-administration of ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of ADCETRIS but it appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. ADCETRIS is not expected to alter the exposure to drugs that are metabolized by CYP3A4 enzymes.
PREGNANCY: Women of childbearing potential should be using two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. There are no data from the use of ADCETRIS in pregnant women, although studies in animals have shown reproductive toxicity. ADCETRIS should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus. If a pregnant woman needs to be treated, she should be clearly advised on the potential risk to the fetus.
LACTATION (breast-feeding): There are no data as to whether ADCETRIS or its metabolites are excreted in human milk, therefore a risk to the newborn/infant cannot be excluded. With the potential risk, a decision should be made whether to discontinue breast-feeding or discontinue/abstain from therapy with ADCETRIS.
FERTILITY: In nonclinical studies, ADCETRIS treatment has resulted in testicular toxicity, and may alter male fertility. Men being treated with this medicine are advised not to father a child during treatment and for up to 6 months following the last dose.
ADVERSE REACTIONS
Serious adverse drug reactions were: pneumonia, acute respiratory distress syndrome, headache, neutropenia, thrombocytopenia, constipation, diarrhea, vomiting, nausea, pyrexia, peripheral motor neuropathy, peripheral sensory neuropathy, hyperglycemia, demyelinating polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome.
In the clinical studies of ADCETRIS, adverse reactions defined as very common (≥1/10) were: infection, upper respiratory tract infection, neutropenia, PN (sensory and motor), cough, dyspneoa, diarrhea, nausea, vomiting, constipation, abdominal pain, alopecia, pruritus, myalgia, arthralgia, fatigue, chills, pyrexia, infusion-related reactions and weight decreased. Adverse reactions defined as common (≥1/100 to <1/10) were: Sepsis/septic shock, herpes zoster, pneumonia, herpes simplex, anemia, thrombocytopenia, hyperglycemia, dizziness, demyelinating polyneuropathy, ALT/AST increased, rash, and back pain.