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Iovance Biotherapeutics to Present at the 37th Annual J.P. Morgan Healthcare Conference

On December 21, 2018 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that the company will present at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Iovance Biotherapeutics, DEC 21, 2018, View Source;p=irol-newsArticle&ID=2381465 [SID1234532223]). Details of the presentation are as follows:

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Presenter: Maria Fardis, Ph.D., President and Chief Executive Officer
Date: Thursday, Jan. 10, 2019
Time: 10:30 a.m. PST
Webcast: A live and archived audio webcast of the presentation will be available in the "Investors" section at www.iovance.com.

Loxo Oncology Announces Initiation of Phase 1/2 Clinical Trial for Highly Selective, Non-Covalent BTK Inhibitor, LOXO-305

On December 21, 2018 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company focused on the development and commercialization of highly selective medicines for patients with genomically defined cancers, reported that it has initiated a Phase 1/2 clinical trial of LOXO-305 (Press release, Loxo Oncology, DEC 21, 2018, View Source [SID1234532222]). LOXO-305 is an investigational, highly selective, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor specifically designed to address acquired resistance and intolerance in patients previously treated with FDA-approved BTK inhibitors.

"We are pleased to initiate the clinical trial for our fourth novel drug candidate," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "FDA-approved BTK inhibitors, which all covalently (irreversibly) bind to their targets, have meaningfully improved the lives of patients with certain B-cell leukemias and lymphomas. However, we are now learning that many patients are discontinuing these therapies due to disease progression or intolerance. When disease progression is caused by a resistance mechanism known as a C481 mutation, we believe that LOXO-305 has the potential to re-induce a response in affected patients. We also believe that the selectivity profile of LOXO-305 has the potential to avoid certain side effects. We look forward to working with our clinical investigators to determine whether LOXO-305 can deliver against these exciting possibilities."

This first-in-human, global, multi-center Phase 1/2 trial will evaluate LOXO-305 as a single agent in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin’s lymphomas (NHL). The primary objective of the Phase 1 portion of the trial is to determine the maximum tolerated dose or recommended phase 2 dose. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Overall Response Rate and Duration of Response, as determined by appropriate histology-specific response criteria). The trial includes a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The Phase 1 dose escalation employs an accelerated titration design, initially enrolling single patient dose cohorts for patients with CLL/SLL or NHL who have received at least two prior lines of therapy and have progressed or are intolerant to standard of care. Based on reported adverse events, the dose escalation may switch to a "3+3" design. In the Phase 2 dose expansion phase, six cohorts are planned to allow for the characterization of the preliminary anti-tumor activity of LOXO-305: 1) CLL/SLL failed prior BTK inhibitor with BTK C481 mutation; 2) CLL/SLL failed prior BTK inhibitor without BTK C481 mutation; 3) Waldenstrom’s macroglobulinemia (WM), mantle cell lymphoma (MCL) or marginal zone lymphoma (MZL) failed prior BTK inhibitor with BTK C481 mutation; 4) WM, MCL or MZL failed prior BTK inhibitor without BTK C481 mutation; 5) CLL/SLL, WM, MCL or MZL intolerant to prior BTK inhibitor; 6) CLL/SLL, WM, MCL or MZL failed prior BTK inhibitor with unknown BTK C481 mutation status and other CLL/SLL, WM, CML, MZL or other NHL patients not meeting the definitions of Cohorts 1 through 5.

About LOXO-305
LOXO-305 is an investigational, novel, highly selective non-covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia, mantle cell lymphoma and marginal zone lymphoma. Currently available BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies has been limited by acquired resistance, most commonly through BTK C481 mutations, and intolerance, due to off target inhibition of other cellular targets. LOXO-305 was designed to reversibly bind BTK, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors. Interested patients and physicians can contact the Loxo Oncology Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email [email protected].

Novartis successfully completes acquisition of Endocyte

On December 21, 2018 Novartis reported that it has completed the acquisition of Endocyte, Inc., a US-based biopharmaceutical company focused on developing radioligand and CAR-T therapies for cancer treatment (Press release, Novartis, DEC 21, 2018, View Source [SID1234532220]).

Novartis receives European Commission (EC) approval for expanded indication for Kisqali® (ribociclib)

On December 21, 2018 Novartis reported that the European Commission (EC) approved an expanded indication for Kisqali (ribociclib), the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent and sustained efficacy compared to endocrine therapy alone (Press release, Novartis, DEC 21, 2018, View Source [SID1234532215]). Kisqali is now approved in the European Union (EU) for the treatment of women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer in combination with fulvestrant as initial endocrine-based therapy and in women who have received prior endocrine therapy. Kisqali is also now approved in combination with endocrine therapy and a luteinising hormone-release hormone agonist (LHRH) for pre- and perimenopausal women with HR+/HER2- locally advanced or metastatic breast cancer.[1]

EU approval follows a positive opinion granted in November by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based on MONALEESA-3 and MONALEESA-7 clinical trials, which demonstrated clinical benefit of Kisqali-based regimens, regardless of combination partner or menopausal status, as first or second-line treatment.[1] Read more about the positive CHMP opinion and the MONALEESA-3 and MONALEESA-7 clinical trial results here.

Important Safety Information from the Kisqali EU SmPC
Kisqali (ribociclib) is a prescription medicine approved in combination with an aromatase inhibitor or fulvestrant as initial endocrine – based therapy or following disease progression on endocrine therapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if Kisqali is safe and effective in children or adolescents. Kisqali can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Kisqali is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. Kisqali can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking Kisqali and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking Kisqali, patients should tell their health care provider if they are pregnant, or plan to become pregnant as Kisqali can harm an unborn baby. Females who are able to become pregnant and who take Kisqali should use highly effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali. Do not breastfeed during treatment with Kisqali and for at least 3 weeks after the last dose of Kisqali. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with Kisqali. Patients should avoid grapefruit or grapefruit juice while taking Kisqali. The most common side effects (incidence >=20%) include infections, white blood cell count decreases, headache, cough, nausea, tiredness, diarrhea, vomiting, constipation, hair loss and rash. The most common Grade 3/4 side effects (incidence >5%) were infections, low neutrophils, low leukocytes, low red blood cells, abnormal liver function tests, low lymphocytes, low phosphate levels and vomiting. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

FDA approves longer-acting calaspargase pegol-mknl for ALL

On December 20, 2018 Servier reported the the Food and Drug Administration approved calaspargase pegol-mknl (ASPARLAS, Servier Pharmaceuticals LLC), an asparagine specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years (Press release, Servier, DEC 20, 2018, View Source [SID1234645703]). This new product provides for a longer interval between doses compared to other available pegaspargase products.

Approval was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity above the level of 0.1 U/mL when using calaspargase pegol-mknl, 2500 U/m2 intravenously, every 3 weeks. The pharmacokinetics of calaspargase pegol-mknl were studied when administered in combination with multiagent chemotherapy in 124 patients with B-cell lineage ALL.

The most common (incidence ≥ 10%) grade ≥ 3 adverse reactions were elevated transaminase, increased bilirubin, pancreatitis, and abnormal clotting studies. In a randomized trial, the safety profile of calaspargase pegol-mknl administered every 3 weeks was similar to that of pegaspargase administered every 2 weeks.

The recommended calaspargase pegol-mknl dose is 2,500 units/m2 intravenously administered at a minimum dosing interval of every 21 days.

View full prescribing information for ASPARLAS.

Calaspargase pegol-mknl received FDA orphan product designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

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Check out recent approvals at the OCE’s podcast, Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.).