On December 11, 2017 Kite, a Gilead Company (Nasdaq: GILD), reported updated results from the ongoing Phase 1/2 ZUMA-3 study of KTE-C19, a CD19 chimeric antigen receptor T (CAR T) cell therapy, which is investigational for the treatment of adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL) (Press release, Kite Pharma, DEC 11, 2017, View Source;p=irol-newsArticle&ID=2322221 [SID1234522565]). With a minimum of eight weeks of follow-up, 71 percent of ALL patients (n=17/24) who received a single infusion of KTE-C19 achieved complete tumor remission (complete remission (CR) or CR with incomplete hematological recovery). The ZUMA-3 study results were presented in an oral session at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This press release features multimedia. View the full release here: View Source

ALL is an aggressive type of blood cancer which can also involve the lymph nodes, spleen, liver, central nervous system and other organs.

"Approximately half of new ALL cases occur in adults age 20 or older and a majority of adult ALL patients relapse and have poor subsequent outcomes," said Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Fla. "The deep remissions seen with these early study results offer promise that adults with this aggressive disease may benefit from personalized cell therapy with KTE-C19. Pending further clinical evaluation, this has the potential to be an advance for adults with no other treatment options."

ZUMA-3 is an ongoing multicenter Phase 1/2 study in patients with ALL whose disease is refractory to or has relapsed following standard chemotherapy or hematopoietic stem cell transplantation. The objectives of the study are to evaluate the safety and efficacy of KTE-C19 in this patient population.

At the time of data cutoff, 24 patients were evaluable for response. KTE-C19 demonstrated a 71 percent (n=17/24) rate of complete remission, with 100 percent of responders having no detectable minimal residual disease, including in those with high tumor burden and high risk genetic abnormalities.

In the safety analysis of 29 patients, adverse events were consistent with the known toxicities of CD19 CAR T treatment, including Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities in 28 percent (n=8/29) and 52 percent of patients (n=15/29), respectively. Two patients receiving KTE-C19 died due to adverse events, including one patient with a cerebrovascular accident not related to KTE-C19 treatment approximately seven weeks after treatment and a previously reported patient who experienced fatal CRS.

"We believe personalized cell therapy has the potential to become a cornerstone of cancer treatment and are rapidly advancing CAR T studies in ALL and in other cancers," said David Chang, MD, PhD, Worldwide Head of Research and Development and Chief Medical Officer at Kite. "ZUMA-3 is reflective of our continued commitment to cell therapy cancer treatment and we are pleased to see these early results for people living with ALL."

KTE-C19 for ALL is investigational and has not been proven safe or efficacious.

On December 11, 2017 Oscotec reported that shares of Oscotec rebounded on the company’s announcement that it has launched a clinical trial in the U.S. on SKI-G-801, a treatment for acute myeloid leukemia (AML) (Press release, Oscotec, DEC 11, 2017, View Source [SID1234573544]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The biotech company said in a public regulatory filing on Monday that its phase-1 clinical trial on SKI-G-801 will begin at six U.S. hospitals.

Oscotec’s shares, which had slid since Dec. 4, rebounded to 10,250 won ($9.4) as of noon on Monday, up 150 won from the previous trading day. Compared with early this year’s stock price of 7,390 won per share, it was up 38 percent.

SKI-G-801 is a treatment that selectively inhibits fms-like tyrosine receptor kinase 3 (FLT3). The company hopes that the new drug candidate will lower side effects and recurrence rate, compared to existing chemotherapies.

The U.S. study will check safety and drug tolerance, after administering SKI-G-801 to recurring or non-reacting AML patients and raising doses in a phased way. The trial will also test the drug’s appropriate doses and efficacy in AML patients with FLT3 mutations.

"Compared to the existing FLT3 inhibitors, SKI-G-801 has excellent pharmacologic activation and long-acting efficacy. Besides, we confirmed its efficacy on FLT3 mutations, which existing inhibitors had no effectiveness, as well as in the drug-resistant environment," Oscotec said.

It went on to say,"If we confirm the safety, drug tolerance, and oncolytic efficacy in the clinical trial, we expect that we will be able to transfer our technology to a multinational pharmaceutical company."

In July 2015, Oscotec transferred its investigational non-small cell lung cancer therapy YH25448 to Yuhan Corp. under an income-sharing contract.

Oscotec’s revenue reached 3.25 billion won ($2.99 million) in the first three quarters this year, with an operating loss of 992 million won.

Its flagship product is InduCera, a material for bone transplant, which takes up about 30 percent of the total sales.

On December 11, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company") reported results from an analysis performed on a large U.S. library of samples from 865 multiple myeloma patients which showed that twenty-five percent of patients had CD33 expression on their multiple myeloma cells (Press release, Actinium Pharmaceuticals, DEC 11, 2017, View Source [SID1234522539]). Actinium is currently conducting a Phase 1 clinical trial for its Actimab-M drug candidate in patients with refractory multiple myeloma. Actinium is the first and only company thus far to have a CD33 targeted therapy for multiple myeloma and the results from this analysis provide further rationale for the Company’s myeloma initiative.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This analysis was the first of its kind to analyze such a large, U.S. based patient sample library as previous studies exploring CD33 expression in multiple myeloma looked at significantly smaller sample sizes from established multiple myeloma cell lines. Patient samples at initial diagnosis were assessed for CD33 expression and CD33 expression was stratified with CD33 expression greater than 40% considered high and greater than 60% very high. The analysis showed that 61.6% of patients in the dataset had high CD33 expression and 41% of patients had very high CD33 expression which translates to approximately fifteen percent of the overall multiple myeloma sample population.

The online abstract can accessed through the following link:
View Source

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "It is generally believed that expression of CD33 on multiple myeloma plasmocytes is in line with the low levels of expression in cells of the lymphoid lineage. The results from this study confirm that CD33 is expressed in a significant sub-set of multiple myeloma patients. Given that CD33 expression levels have been found to be high or very high in a large percentage of patients that do express the antigen, we have great confidence that our Actimab-M drug candidate, which uses an anti-CD33 antibody, can have a beneficial impact on these patients. In a disease like multiple myeloma, which remains incurable, we believe it is important to explore new therapeutic modalities and use of our CD33 targeting ARC or Antibody Radio-Conjugate is supported by these results. Additionally, myeloma cells are sensitive to radiation and targeting them using an ARC like Actimab-M may provide further advantages."

Patients that relapsed were also assessed for CD33 expression and 27.1% of relapsed patients were found to have CD33 expression with 58.3% of these patients having very high expression at initial diagnosis and relapse.

About Actimab-M

Actimab-M is being investigated in patients with refractory multiple myeloma. Multiple myeloma is a currently incurable cancer of plasma cells, which are white blood cells that produce antibodies. Actimab-M is currently being studied in a Phase 1 dose escalation study in up to 12 patients that is designed to establish safety, maximum tolerable dose and proof of concept. Actimab-M is an ARC or Antibody Radio-Conjugate that consists of Actinium-225, an alpha-emitting radioisotope coupled to the anti-CD33 monoclonal antibody, lintuzumab. CD33 has been shown to be expressed on myeloma plasmocytes in 25% of multiple myeloma patients and up to 35% of multiple myeloma patients and has also shown to be correlated with poorer outcomes.

On December 11, 2017 Verastem, Inc. (NASDAQ: VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported the presentation of new preclinical and Phase 1 clinical data from an investigator-sponsored study evaluating the safety and activity of oral duvelisib in combination with romidepsin (Istodax) or bortezomib (Velcade) in relapsed or refractory T-cell lymphomas (TCL) at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2017 Annual Meeting held December 9-12, 2017 in Atlanta (Press release, Verastem, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322203 [SID1234522563]). Duvelisib is a first-in-class oral dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma which is currently being developed for the treatment of relapsed or refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) and Follicular Lymphoma (FL). In addition, duvelisib is being studied in other hematologic malignancies including both peripheral and cutaneous T cell lymphoma (TCL).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data presented today at ASH (Free ASH Whitepaper) demonstrate that oral duvelisib, combined with either romidepsin or bortezomib, has an acceptable safety profile in patients with relapsed or refractory TCL with response rates, while still preliminary, that appear promising when compared to those seen with currently approved therapies," said Steven Horwitz, MD, Memorial Sloan Kettering Cancer Center (MSKCC), co-principal investigator of the Phase 1 study, and lead author of the oral presentation. "We were especially pleased to see that these response rates were even higher in patients with peripheral TCL (PTCL), a rare and aggressive type of non-Hodgkin lymphoma. These clinical results were further bolstered by important preclinical findings showing duvelisib’s cell killing activity in vitro and its ability to promote beneficial changes within the in vivo tumor microenvironment."

"The preclinical and Phase 1 results reported today by the team at MSKCC are important because they provide further validation for our continued expansion of the duvelisib development program into T-cell malignancies including PTCL," said Diep Le, MD, PhD, Chief Medical Officer of Verastem. "Overall, our data presentations at ASH (Free ASH Whitepaper) this year continue to build upon the strong foundation of preclinical research and clinical investigation for Verastem’s product candidates, demonstrating their anti-cancer activity, either alone or in combination with other agents, across a wide variety of hematologic malignancies."

Phase 1 Safety and Activity Results
This multicenter, Phase I trial is comprised of parallel arms evaluating oral duvelisib in combination with romidepsin (arm A) or bortezomib (arm B) in patients with relapsed/refractory TCL, including PTCL and cutaneous T-cell lymphoma (CTCL). Oral duvelisib was dosed at 25mg, 50mg, or 75mg twice-daily (BID) on days 1-28. Romidepsin 10mg/m2 was dosed on Days 1, 8, and 15 (arm A) or bortezomib 1mg/m2 on Days 1, 4, 8, and 11 (arm B), both cohorts on 28-day cycles.

In arm A, there were 15 patients evaluable for efficacy (PTCL, n=11; CTCL, n=4). Of these, nine responded (4 complete responses (CR) and 5 partial responses (PR) for an overall response rate (ORR) of 60%. Seven of the 11 patients with PTCL responded (4 CR and 3 PR) for an ORR of 64%. Among the 9 patients evaluable for safety (25mg, n=3; 50mg, n=3; 75mg, n=3), there were no dose limiting toxicities (DLT), therefore oral duvelisib 75mg BID in combination with romidepsin 10mg/m2 IV was defined as the maximum tolerated dose (MTD). The most common Grade 1/2 adverse events were fatigue (n=9), nausea (n=8), altered taste (n=8) and diarrhea (n=6), rash (n=5), dysphagia (n=4) and anorexia (n=4). The most common Grade 3/4 adverse events were neutropenia (n=6), thrombocytopenia (n=1), lung infection (n=1), pleural effusion (n=1) and hyponatremia (n=1). There were two deaths (sepsis and diffuse alveolar hemorrhage following allogeneic stem cell transplant) that were both assessed as unrelated to study drug.

In arm B, there were 17 patients evaluable for efficacy (PTCL, n=10; CTCL, n=7). Of these, six responded (3 CRs and 3 PRs) for an ORR of 35%. Five of the 10 patients with PTCL responded (3 CRs and 2 PRs) for an ORR of 50%. Among the 14 patients evaluable for safety (25mg, n=6; 50mg, n=3; 75mg, n=5), there was one DLT (pneumonia) in the 25mg group. The MTD was determined to be oral duvelisib 25mg BID in combination with bortezomib 1mg/m2 IV. The most common Grade 1/2 adverse events were diarrhea/colitis (n=11), nausea/vomiting (n=4), chills (n=4) and fatigue (n=4). The most common Grade 3/4 adverse events were ALT and AST elevation (n=6), rash (n=2) and neutropenia (n=2). There was a case of Stevens-Johnson syndrome resulting in death which was assessed by the investigator as possibly related to bortezomib, duvelisib, and trimethoprim-sulfamethoxazole, a medication that was initiated at the start of the study.

A copy of this oral presentation will be available here following the conclusion of the session.

About the Tumor Microenvironment
The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T-cells, myeloid-derived suppressor cells, M2 TAMS, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib and defactinib target the tumor microenvironment as a mechanism of action to potentially improve a patient’s response to therapy.

About Duvelisib
Duvelisib is a first-in-class investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B- and T-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage extension trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL),4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL).5 Both DUO and DYNAMO achieved their primary endpoints and Verastem intends to submit a New Drug Application (NDA) requesting the full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL). Duvelisib is also being developed by Verastem for the treatment of peripheral T-cell lymphoma (PTCL), and is being investigated in combination with other agents through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov

About Focal Adhesion Kinase
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase encoded by the PTK-2 gene that is involved in cellular adhesion and, in cancer, metastatic capability. Defactinib (VS-6063) and VS-4718 are orally available compounds that are potent inhibitors of FAK. Defactinib and VS-4718 utilize a multi-faceted approach to treat cancer by reducing cancer stem cells, enhancing anti-tumor immunity, and modulating the local tumor microenvironment. Defactinib is currently being studied in multiple clinical trials for patients with cancer.

On December 11, 2017 Integra LifeSciences Holdings Corporation (NASDAQ:IART), a leading global medical technology company, reported it will host an Investor Day meeting with analysts and institutional investors in New York City, beginning at 8:00 a.m. EST. Members of Integra’s executive leadership team will discuss the company’s financial performance and outlook (Press release, Integra LifeSciences, DEC 11, 2017, View Source [SID1234522512]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Highlights of today’s conference include:

• Reaffirming 2017 financial guidance as provided on October 26, 2017, including:

Full-year 2017 revenue in the range of $1.165 billion to $1.175 billion, which includes about 4% organic growth

Full-year 2017 adjusted earnings per share in the range of $1.83 to $1.87
• Providing 2018 preliminary revenue estimate in the range of $1.46 billion to $1.48 billion, which includes about 5% organic growth

• Reaffirming 2018 adjusted earnings per share in the range of $2.25 to $2.35, consistent with preliminary estimates provided on October 26, 2017

• Establishing five-year financial targets of approximately $2 billion in revenue and an adjusted EBITDA margin range of 28% to 30%

The company will host a livestream of the presentation and conference materials are available through the Investors section of Integra’s website at www.integralife.com. A replay of the conference will be archived on the company website.