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BeiGene to Present Data on BGB-3111 at the 14th International Conference on Malignant Lymphoma and to Host Conference Call

On June 7, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a clinical-stage biopharmaceutical company developing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported that it will present updates on its BTK inhibitor BGB-3111 in three oral presentations and a poster at the upcoming 14th International Conference on Malignant Lymphoma (14-ICML) (Press release, BeiGene, JUN 7, 2017, View Source [SID1234519469]). 14-ICML will take place June 14-17, 2017, in Lugano, Switzerland. Following its presentations, BeiGene will host an investor call and webcast to discuss the presented data and development program.

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Oral Presentation, Abstract # 059

Title: Bruton’s Tyrosine Kinase (BTK) Inhibitor BGB-3111 Demonstrates High Very Good Partial Response (VGPR) Rate in Patients with Waldenström Macroglobulinemia (WM)

Presenter: Dr. Judith Trotman

Session: Session 4 – Targeting the BCR Pathways
Date & Time: Thursday, June 15, 2017, 4:00 PM CEST
Location: Room A, Cinema Corso and Aula Magna (Lugano University)

Oral Presentation, Abstract # OT06

Title: A Head-to-Head Phase 3 Study Comparing BGB-3111 and Ibrutinib in Patients with Waldenström Macroglobulinemia

Presenter: Dr. Christian Buske

Session: Ongoing Trials
Date & Time: Thursday, June 15, 2017, 6:05 PM CEST
Location: Auditorium (Lugano University)

Oral Presentation, Abstract # 103

Title: Safety and Activity of the Highly Specific BTK Inhibitor, BGB-3111 Plus Obinutuzumab in Patients (Pts) with Follicular Lymphoma (FL) and Chronic Lymphocytic Leukemia (CLL)

Presenter: Dr. Constantine Tam

Session: Session 7 – Advances in CLL
Date & Time: Friday, June 16, 2017, 11:50 AM CEST
Location: Room A, B, Marquee, Cinema Corso and Aula Magna (Lugano University)

Poster, Abstract # 237

Title: High Overall Response Rate with the BTK Inhibitor BGB-3111 in Patients with Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: An Update on Safety and Activity

Presenter: Dr. John Seymour

Session Dates & Times: Wednesday, June 14, 12:30-6:30 PM CEST; Thursday, June 15, 8:30-6:30 PM CEST; Friday, June 16, 8:30-6:30 PM CEST
Location: Marquee

Investor Conference Call

Date & Time: Friday, June 16, 2017, 2:00 PM CEST (8:00 AM EDT, 8:00 PM China Standard Time)

Dial-in Numbers: 1-845-675-0437 or 1-866-519-4004 (US), 400-620-8038 or 800-819-0121 (China), +852 30186771 (Hong Kong), or +65 67135090 (International)

Conference ID Number: 33044427

A live webcast and replay will be available on BeiGene’s investor website, View Source The dial-in replay will be available approximately two hours after the conference and will be available for two days following the event. It can be accessed by dialing 1-646-254-3697 (US), 400-632-2162 (China), +852 30512780 (Hong Kong), or +61 2 8199 0299 (International).

About BGB-3111

BGB-3111 is a potent and highly selective investigational small molecule inhibitor of BTK. BGB-3111 has demonstrated higher selectivity against BTK than ibrutinib (the only BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency) based on biochemical assays, higher exposure than ibrutinib based on their respective Phase I experience, and sustained 24-hour BTK occupancy in both the blood and the lymph node.

Eureka Therapeutics And City Of Hope Announce Agreement To Conduct Phase 1 Clinical Trial Of Investigational ET1402L1 CAR-T Therapy In Liver Cancer

On June 7, 2017 Eureka Therapeutics Inc., a biotechnology company focused on developing novel T-cell immunotherapies for the treatment of solid tumors, and City of Hope, a world-renowned independent research and cancer and diabetes treatment center, reported that they have reached agreement to conduct an open-label, dose-escalating Phase 1 clinical trial of ET1402L1-CAR, a potential CAR-T therapy for the treatment of hepatocellular carcinoma, the predominant type of liver cancer (Press release, Eureka Therapeutics, JUN 7, 2017, View Source [SID1234519468]). ET1402L1 is a human antibody, identified from Eureka’s proprietary E-ALPHA phage library, which selectively targets liver cancer cells overexpressing alpha-fetoprotein (AFP).

"We are pleased to be working with Eureka Therapeutics on this unique approach to treating liver cancer with CAR-T therapy" Tweet this

"The clinical trial agreement represents an important milestone for Eureka, as it provides a pathway for treating patients with liver cancer, and it supports our business objectives to develop ET1402L1-CAR in areas of significant unmet medical need," said Cheng Liu, Ph.D., President and Chief Executive Officer of Eureka Therapeutics. "This is a significant step in demonstrating that CAR-T cell therapy can be successfully used to target a major histocompatibility complex (MHC) presented antigen in solid tumors."

Intracellular antigens, which account for the most tumor-specific antigens, are inaccessible by conventional CAR-T therapy. Such antigens which include AFP, however, are processed into peptides and presented by the class I MHC on the surface of tumor cells. A 2017 study (DOI: 10.1158/1078-0432.CCR-16-1203), published by Eureka and City of Hope in Clinical Cancer Research, showed that ET1402L1-CAR T cells can recognize the AFP-MHC complex and launch a potent anti-tumor response, offering a promising new avenue for T cell therapy against solid malignancies.

"We are pleased to be working with Eureka Therapeutics on this unique approach to treating liver cancer with CAR-T therapy," said principal investigator Yuman Fong, M.D., The Sangiacomo Family Chair in Surgical Oncology and chair and professor of the Department of Surgery at City of Hope. "CAR-T therapy has shown remarkable success with liquid tumors. However, the lack of cancer specific cell surface antigens has limited the use of CAR-T therapy to other cancers. The results of this study could have a wide range of applications in other difficult-to-treat solid cancers such as lung and prostate cancer, which have few cell surface markers that are tumor-specific."

"City of Hope has accepted the challenge to bring leading-edge treatments to patients with liver cancer," said investigator Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of City of Hope’s T Cell Immunotherapy Research Laboratory. "We are optimistic that CAR-T therapy can be an important component in treating patients with solid tumors, including liver cancer."

The Phase 1 clinical trial will be led by Fong and Forman. Other collaborating investigators include Christine Brown, Ph.D., Heritage Provider Network Professor in Immunotherapy, John Kessler, M.D., John Park, M.D., Ph.D., Saul Priceman Ph.D., Shirong Wang, M.D., M.P.H., and Susanne Warner, M.D., all of City of Hope in Duarte, California.

About Liver Cancer

Liver cancer is the fifth most prevalent and third most lethal cancer worldwide, with incidence rates on the rise and limited treatment options. Hepatocellular carcinoma is the predominant type of liver cancer, affecting over 700,000 people each year worldwide. Alpha-fetoprotein (AFP) is overexpressed, specifically in liver cancer, making it an ideal target for chimeric antigen receptor (CAR) T cell immunotherapy. However, AFP is intracellularly expressed and secreted, and therefore, not targetable by conventional antibody-based therapies.

Verastem to Present Long-Term Follow-Up Data from the DYNAMO™ Study at the 14th International Conference on Malignant Lymphoma

On June 7, 2017 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported long-term follow-up data from the DYNAMO study, which met its primary endpoint of Overall Response Rate (ORR; p=0.0001) at the final analysis, will be presented at the 14th International Conference on Malignant Lymphoma (ICML), being held June 14-17, 2017 in Lugano, Switzerland (Press release, Verastem, JUN 7, 2017, View Source [SID1234519465]). DYNAMO is a Phase 2 clinical study evaluating the safety and efficacy of duvelisib monotherapy in patients with indolent non-Hodgkin lymphoma (iNHL) who were refractory to both rituximab and chemotherapy or radioimmunotherapy. Duvelisib is an investigational dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma that has demonstrated clinical activity as an oral monotherapy in multiple hematologic cancers, including chronic lymphocytic leukemia (CLL), iNHL, and T-cell lymphoma.

The long-term follow-up results from the study will be highlighted in an oral presentation titled, "DYNAMO: A Phase 2 Study Demonstrating the Clinical Activity of Duvelisib in Patients with Double-Refractory Indolent Non-Hodgkin Lymphoma," given by Pier Luigi Zinzani, MD, PhD, University of Bologna Institute of Hematology, on Thursday, June 15, 2017 at 15:40 CET (9:40 ET) in Room A, Cinema Corso and Aula Magna (Lugano University).
"The data we are presenting at ICML help fill in the clinical picture for those patients who receive duvelisib over a longer period," noted Dr. Zinzani. "Not only did duvelisib monotherapy continue to show robust and durable responses in double-refractory iNHL, but longer-term exposure to duvelisib did not reveal any unexpected safety findings. These results suggest duvelisib has favorable benefit-risk in double-refractory iNHL, and may provide an important new treatment option for a population in need of new targeted therapies."

Patients enrolled in DYNAMO all had double-refractory iNHL and a median of 3 prior anticancer regimens. Of the 129 patients enrolled, 61 responded (1 complete response [CR], 60 partial responses [PR]), for an overall response rate (ORR) of 47%, as determined by an independent review committee. The ORR in each of the three disease subgroups included: 43% in follicular lymphoma (n=83); 68% in small lymphocytic lymphoma (n=28); and 33% in marginal zone lymphoma (n=18). Responses generally occurred shortly after the start of treatment (median 2 months). Notably, 88% of all patients treated with duvelisib had a reduction in the size of their target lymph nodes. Overall, median duration of response was 10 months, median progression-free survival was 9 months, and median overall survival was 27.8 months.

With additional follow-up (median 18 months), the safety profile of duvelisib monotherapy remains consistent with what has been previously reported in iNHL and other hematologic malignancies. The most common Grade ≥ 3 adverse events were hematologic in nature (neutropenia 30%, thrombocytopenia 15%, anemia 14%). Diarrhea was the most frequently reported nonhematologic adverse event (47%; 15% Grade ≥ 3). As expected in a heavily pretreated and refractory patient population, infections of all types and grades were observed (56%). Pneumonitis and colitis, events previously described with duvelisib, remained relatively uncommon (9% and 5%, respectively). Treatment discontinuations attributed to the most common adverse events were infrequent, suggesting that these events were generally manageable.

"The clinical activity and durability of responses observed in the DYNAMO study seen across a range of highly-refractory disease subtypes, together with the well-characterized and manageable safety profile, highlight the potential of this drug in lymphoid malignancies," said Hagop Youssoufian, MSc, MD, Head of Hematology and Oncology Development at Verastem. "What I find really encouraging, is that we saw these results in patients refractory to both rituximab and chemotherapy, a specific population with unmet medical need."

Following conclusion of Dr. Zinzani’s presentation, a copy of the presentation will be available here.

More About the Phase 2 DYNAMO Study
DYNAMO is a Phase 2, single-arm study, which evaluated the efficacy and safety of duvelisib 25 mg twice daily as monotherapy in 129 iNHL patients, including follicular lymphoma (n=83), small lymphocytic lymphoma (n=28), and marginal zone lymphoma (n=18) whose disease has progressed and are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was ORR as assessed by an independent review committee.

About the Tumor Microenvironment
The tumor microenvironment encompasses multiple tumor and non-tumor cell populations and an extracellular matrix that support cancer cell survival. This includes immunosuppressive regulatory T-cells, myeloid-derived suppressor cells, tumor-associated macrophages, cancer-associated fibroblasts, and extracellular matrix proteins that can hamper the entry and therapeutic benefit of cytotoxic T-cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s product candidates, including duvelisib and defactinib, also target the tumor microenvironment to potentially improve response to therapy.

About Duvelisib
Duvelisib is an 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-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 clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory CLL,4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory iNHL that achieved its primary endpoint of ORR.5 Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T-cell lymphoma.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

TRILLIUM EXPANDS CLINICAL TRIAL WITH TTI-621 TO INCLUDE COMBINATION WITH PD-1 BLOCKADE

On June 7, 2017 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company, reported that based upon promising early evidence of anti-tumor activity in patients with both myeloid and lymphoid malignancies, it has further expanded its current intravenous dosing trial of TTI-621, an IgG1 SIRPaFc fusion protein targeting CD47 (Press release, Trillium Therapeutics, JUN 7, 2017, View Source [SID1234519464]).

Changes to the trial include:

An additional cohort of patients with Hodgkin lymphoma treated with a combination of TTI-621 and the PD-1 checkpoint inhibitor nivolumab
Two additional cohorts of patients with T- and B-cell acute lymphoblastic leukemia and small cell lung cancer treated with TTI-621 monotherapy
Cautious exploration of dose-intensification, building upon the observation of good overall tolerability associated with attenuated thrombocytopenia over successive weekly doses of TTI-621
Increasing the size of cohorts exhibiting early evidence of clinical benefit
"Having observed meaningful objective responses among multiple treatment-refractory cancer patients, we are now expanding the trial’s scope with additional focused enrollment to extend these preliminary observations and to seek promising new signals of activity—both with TTI-621 monotherapy, with rituximab, and in a novel combination with T-cell checkpoint inhibition," said Trillium’s Chief Medical Officer, Dr. Eric Sievers. "With emerging data linking CD47 blockade with T cell activation, we are excited to pursue the combination of TTI-621 and nivolumab in an attempt to optimally engage both the innate and adaptive arms of the immune system to generate a robust and enduring anti-tumor response."

Takeda and Seattle Genetics Announce Lancet Publication of Phase 3 ALCANZA Clinical Trial Data of ADCETRIS® (Brentuximab Vedotin) for CD30-Positive Cutaneous T-Cell Lymphoma

On June 7, 2017 Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc. (NASDAQ: SGEN) reported that data from the randomized Phase 3 ALCANZA clinical trial evaluating ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) were published in the journal Lancet (Press release, Seattle Genetics, JUN 7, 2017, View Source [SID1234519463]). Data were previously presented in an oral session at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 which is expressed on CTCL lesions in approximately 50 percent of patients with the disease. ADCETRIS is currently not approved for the treatment of CTCL.

"Today’s publication of the positive results of the ALCANZA trial is another milestone for our brentuximab vedotin clinical program. We plan to submit the data to regulatory bodies around the world, and if approved, ADCETRIS would be a potential new treatment option for patients with CD30-positive CTCL, a rare, debilitating and often difficult to treat form of cancer," said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. "We are encouraged by the data we’ve seen from our robust ongoing clinical investigation program of ADCETRIS in CD30-positive lymphomas, and are committed to bringing this important therapy to patients."

"The ALCANZA study is the first randomized Phase 3 clinical trial to evaluate a novel agent versus standard of care in CTCL, an incurable and disfiguring disease with few treatment options that achieve durable responses," said Bob Lechleider, M.D., Senior Vice President, Clinical Development of Seattle Genetics. "The data from the ALCANZA trial provide compelling evidence that CTCL patients treated with ADCETRIS had superior outcomes across the primary and all secondary endpoints assessed in the study compared to patients in the control arm who were treated with a standard of care agent. These data demonstrate the potential of ADCETRIS to change the treatment landscape of CTCL."

ALCANZA is a randomized, open-label Phase 3 study designed to evaluate single-agent ADCETRIS versus a control arm of investigator’s choice of the standard of care therapies methotrexate or bexarotene, in patients with CD30-positive CTCL. The manuscript highlights data from the trial which achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.0001). Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the ADCETRIS arm. The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.

Based on the study results, Takeda plans to begin to submit data from the ALCANZA trial to regulatory agencies in its territories in 2017. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to ADCETRIS for the treatment of the most common subtypes of CTCL, mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Seattle Genetics plans to submit these data as part of a supplemental Biologics License Application to the FDA in mid-2017. The ALCANZA trial received a Special Protocol Assessment (SPA) agreement from the FDA and scientific advice from the European Medicines Agency (EMA).

About CTCL

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. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs. According to published literature, CD30 is expressed on CTCL lesions in approximately 50 percent of patients with the disease.

The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma for which a supplemental BLA is planned in mid-2017.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. 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 for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.

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 sALCL. The European Commission extended the current conditional marketing authorization 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 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

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.