On December 11,2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the phase III IMmotion151 study met its co-primary endpoint of investigator-assessed progression free survival (PFS), and demonstrated that the combination of atezolizumab and Avastin showed statistically significant improvement in PFS compared with sunitinib in patients whose disease expressed PD-L1 (programmed death-ligand 1: Expression ≧1%) for the first-line treatment of locally advanced or metastatic renal cell carcinoma (RCC)(Press release, Chugai, DEC 11, 2017, View Source [SID1234522503]).

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Observations of as pre-specified subgroup analysis of the atezolizumab and Avastin combination indicated that, in people whose disease expressed PD-L1, a numerical difference favoring atezolizumab and Avastin group was seen across all patient risk factor groups (favorable, intermediate and poor) compared to sunitinib; however, due to the study design these data could not be assessed for statistical significance and are descriptive only. As data is not fully matured, analysis for another co-primary endpoint of overall survival (OS) as well as the assessment of secondary endpoints is ongoing. Safety for the atezolizumab and Avastin combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the Phase II IMmotion150 study. No new safety signals were identified with the combination. The data of the IMmotion151 study will be presented at an upcoming oncology conference in 2018.

"Avastin is currently approved overseas for the treatment of RCC in combination with interferon. We are pleased that IMmotion151 study in which Japanese patients are participating showed the combination of atezolizumab and Avastin demonstrated an improvement in PFS," said Dr. Yasushi Ito, Senior Vice President and Head of Project & Lifecycle Management Unit. "We are committed to prepare the filing for approval in order to deliver both drugs to patients as a new treatment option as soon as possible."

About the IMmotion151 Study
A global phase III, multi-center, open label, randomized study designed to evaluate the efficacy and safety of atezolizumab plus Avastin compared to sunitinib in previously untreated patients with locally advanced or metastatic RCC.

The study’s co-primary endpoints include PFS in people whose tumors expressed PD-L1 (PD-L1 expression ≧1%) on immune cells (IC) and OS in intent to treat (ITT) population. PD-L1 expression was assessed using an immunohistochemistry (IHC) test, SP142 developed by Roche.

Depending on the presence of one or several of five risk factors, patients are classified in one of the three risk groups: "Favorable" with 0 risk factors, "Intermediate" with 1-2 risk factors and "Poor" with 3 or more factors.
Study design
915 patients were randomized into atezolizumab plus Avastin or sunitinib arm in a 1:1 ratio to receive treatment according to each group’s treatment regimen.
In Japan, Avastin is not approved for the treatment of RCC.

About atezolizumab
Atezolizumab is a monoclonal antibody designed to target a protein called PD-L1 (programmed death ligand-1), which is expressed on tumor cells and tumor-infiltrating immune cells. PD-L1 binds to PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this coupling, atezolizumab may enable to release the suppression of T cells and promotes T cells to effectively attack tumor cells.
Atezolizumab (overseas brand name: TECENTRIQ) is an anti-PD-L1 immune checkpoint inhibitor. In US, atezolizumab was granted accelerated approval for the second line treatment of locally advanced or metastatic urothelial carcinoma (mUC) by the FDA in May, 2016. The FDA also approved atezolizumab as the treatment of metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy in October, 2016 and granted accelerated approval as the first line treatment of locally advanced or mUC who are ineligible for cisplatin chemotherapy in April, 2017. In EU, EMA approved atezolizumab for the second line treatment of locally advanced or mUC, the treatment of metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy and the first line treatment of locally advanced or mUC who are ineligible for cisplatin chemotherapy in September, 2017. In Japan, the new drug application of atezolizumab for the treatment of unresectable advanced or recurrent NSCLC was filed in February, 2017.

Trademarks used or mentioned in this release are protected by law

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On December 11, 2017 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported new efficacy and safety data from the ongoing Phase 1 dose-escalation and expansion study evaluating oral ivosidenib (AG-120) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) and an isocitrate dehydrogenase-1 (IDH1) mutation (Press release, Agios Pharmaceuticals, DEC 11, 2017, View Source [SID1234522571]). Ivosidenib is an investigational, first-in-class, oral, targeted inhibitor of the mutant IDH1 enzyme. Data in an oral session at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition demonstrated a complete response (CR) and CR with partial hematologic recovery (CRh) rate of 30.4% and an overall response rate (ORR) of 41.6% in the primary analysis set of 125 patients with R/R AML who received ivosidenib at 500 mg once daily and received their first dose at least 6 months prior to the May 12, 2017 analysis cutoff date. The CR+CRh rate is the primary endpoint of the study.

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"New ivosidenib data from the expansion phase of the Phase 1 study is compelling and demonstrates impressive single-agent efficacy with durable responses in these high-risk relapsed or refractory AML patients," said Courtney DiNardo, M.D., lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "Important measures of clinical benefit for patients treated with ivosidenib were also observed and include increases in transfusion independence and a decrease in the frequency of comorbidities such as febrile neutropenia and infections in responding patients."

A total of 258 patients with advanced hematologic malignances and an IDH1 mutation were treated on the Phase 1 study, which included 78 patients in the dose-escalation portion and 180 patients from four dose-expansion Arms. Enrollment to the study is closed. This is the first presentation of data from the dose-expansion portion of the study. Safety data reported include all treated patients, and includes those who received ivosidenib at total daily doses ranging from 200 mg to 1200 mg in dose-escalation and 500 mg daily in dose expansion. A maximum tolerated dose was not reached in the dose-escalation portion of the trial. The primary analysis set is comprised of 125 R/R AML patients (92 patients from Arm 1 of the expansion and 33 patients from the dose-escalation who met the eligibility criteria for Arm 1 and received ivosidenib at 500 mg once daily) who were enrolled at least 6 months prior to the primary analysis cutoff date of May 12, 2017. The median age of these patients is 67 (ranging from 18-87), and the median number of prior regimens is two (ranging from one to six).

"These data form the core of the efficacy analysis for our ivosidenib NDA submission, which is on track for the end of the year," said Chris Bowden, M.D., chief medical officer of Agios. "We believe that these data validate the potential for ivosidenib to be a first-in-class therapy for patients with R/R AML and an IDH1 mutation."

Safety Data
A safety analysis conducted for all 258 treated patients as of the data cut-off showed that ivosidenib continues to demonstrate a favorable safety profile. The most common adverse events (AEs) regardless of causality were diarrhea (33.3%), leukocytosis (30.2%), nausea (29.5%), fatigue (28.7%) and febrile neutropenia (25.2%).

Among the 125 R/R AML patients from the primary analysis set, adverse events of interest were the following:

8% reported Grade ≥3 leukocytosis, which was managed with hydroxyurea. No cases were fatal.
8% reported Grade 3 QT prolongation. Ivosidenib was reduced in one patient and held in five patients (for any grade of QT prolongation), and no cases were Grade 4 or fatal.
9.6% reported IDH-differentiation syndrome (IDH-DS), which was managed with corticosteroids and diuretics. None were Grade 4 or fatal.
Efficacy Data
Data from 125 R/R AML patients from the primary analysis set demonstrated a combined CR+CRh rate of 30.4% [95% CI 22.5, 39.3], which is the primary endpoint of the study. The CR rate was 21.6% (27 of 125 patients) [95% CI 14.7, 29.8] and the CRh rate was 8.8% (11 of 125 patients). CRh (complete remission with partial hematological recovery) is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

Overall response rate (ORR) was 41.6% (52 of 125 patients).
Median duration of response was 9.3 months [95% CI 5.6, 18.3] for patients who achieved a CR, 8.2 months [95% CI 5.5, 12.0] for patients who achieved a CR/CRh and 6.5 months [95% CI 4.6, 9.3] for all patients who responded.
Median time to first response was 1.9 months (0.8-4.7) for all patients who responded, median time to CR was 2.8 months (0.9-8.3) for patients who achieved a CR, and median time to CR/CRh was 2.7 months (0.9-5.6) for patients who achieved a CR/CRh.
At the time of the data cut-off, median overall survival (OS) as observed in the study has not yet been reached for patients who achieved a CR/CRh. OS was 9.3 months [95% CI 3.7, 10.8] for non-CR/CRh responders, 3.9 months [95% CI 2.8, 5.8] for non-responders, and 8.8 months [95% CI 6.7, 10.2] overall.
Of the patients who were transfusion dependent at baseline and achieved a CR, 100% became independent of platelet transfusions and 84.6% became independent of red blood cell (RBC) transfusions during any 56-day post baseline period.
Of the patients who were transfusion dependent at baseline and achieved a CRh, 71.4% became independent of platelet transfusions and 75.0% became independent of RBC transfusions during any 56-day post baseline period. Transfusion independence was also seen among non-CR/CRh responders and non-responders. Non-CR/CRh responders include patients with CR with incomplete hematologic recovery (CRi), CR with incomplete platelet recovery (CRp) and morphologic leukemia-free state (MLFS) who are not CRh.
Response in Untreated AML and MDS
An efficacy analysis was also presented for 34 untreated AML patients not eligible for standard of care therapies in expansion Arm 2 and from dose escalation whose starting dose was 500 mg daily and 12 myelodysplastic syndrome (MDS) patients in expansion Arm 3 and from dose escalation whose starting dose was 500 mg daily.

Data from 34 untreated AML patients demonstrated a 55.9% ORR and a CR rate of 20.6%. The median duration of response was 9.2 months [95% CI 1.9, NE], and median duration of CR has not yet been reached.
Data from 12 MDS patients demonstrated a 91.7% ORR and a CR rate of 41.7%.
Clinical Development in AML
Ivosidenib continues to be studied in the following ongoing clinical trials in AML:

Phase 3 AGILE study evaluating the safety and efficacy of ivosidenib + azacitidine vs. placebo + azacitidine in adults with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy
Phase 1b study of either ivosidenib or enasidenib in combination with standard induction and consolidation chemotherapy in newly diagnosed AML
Phase 1/2 study of either ivosidenib or enasidenib in combination with azacitidine in newly diagnosed AML
Agios is on track to file a New Drug Application (NDA) for ivosidenib with the U.S. Food and Drug Administration by the end of 2017.

About the Phase 1 Trial for Ivosidenib in Advanced Hematologic Malignancies
Ivosidenib (AG-120) is being evaluated in an ongoing Phase 1 trial that includes a dose-escalation phase and four expansion arms, including:

Arm 1: IDH1 mutant positive AML patients who relapsed after bone marrow transplantation, are in second or later relapse, refractory to initial induction or reinduction treatment, or who relapse within one year of initial treatment, excluding patients with favorable-risk status
Arm 2: untreated IDH1 mutant positive AML patients who are not candidates for standard-of-care chemotherapy
Arm 3: patients with other non-AML IDH1 mutant, relapsed or refractory advanced hematologic malignancies
Arm 4: patients with relapsed IDH1 mutant positive AML not eligible for arm 1 who have failed or are unable to receive standard of care
About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society, the median age of onset is 66. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

Investor Event and Webcast Information
Agios will host an investor event on Monday, December 11, 2017 beginning at 8:00 p.m. ET in Atlanta to review data presented at ASH (Free ASH Whitepaper). The event will be webcast live and can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com.

On December 11, 2017 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that new clinical data from ongoing Phase 1 a/b trials for its CD47-blocking agent, TTI-621 (SIRPa-IgG1 Fc), were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 59th Annual Meeting, December 9-12, in Atlanta (Press release, Trillium Therapeutics, DEC 11, 2017, View Source [SID1234522536]).

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Poster Presentation 4076: A Single Direct Intratumoral Injection of TTI-621 (SIRPaFc) Induces Antitumor Activity in Patients with Relapsed/Refractory Mycosis Fungoides and Sézary Syndrome: Preliminary Findings Employing an Immune Checkpoint Inhibitor Blocking the CD47 "Do Not Eat" Signal. Presenter: Christiane Querfeld, MD, PhD, City of Hope National Medical Center.

This poster presentation highlighted preliminary safety and anti-tumor activity of intratumoral TTI-621 administration in highly pretreated patients with relapsed or refractory mycosis fungoides or Sézary syndrome. Intratumoral injection was well tolerated, with no dose-limiting toxicity observed. A rapid reduction in CAILS scores, which measures local lesion responses, was observed in 9 out of 10 mycosis fungoides patients and a reduction in circulating leukemic Sézary cells was observed in 3 out of 3 patients. Several patient profiles were presented which demonstrate clinical responses in disfiguring lesions, in some cases after a single dose of TTI-621. Collectively, the data demonstrate that cutaneous T-cell lymphoma (CTCL) appears biologically responsive to intratumoral injections of TTI-621, and enrollment in this trial (NCT02890368) is continuing.

Poster Presentation 4116: TTI-621 (SIRPaFc), an Immune Checkpoint Inhibitor Blocking the CD47 "Do Not Eat" Signal, Induces Objective Responses in Patients with Advanced, Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL). Presenter: Stephen Ansell, MD, PhD, Division of Hematology, Mayo Clinic.

This poster presentation summarized the overall safety profile of intravenous TTI-621 in patients with relapsed/refractory hematologic malignancies and preliminary anti-tumor activity in patients with diffuse large B-cell lymphoma (DLBCL). Weekly infusions of TTI-621 were shown to be well tolerated, and notably, transient thrombocytopenia was attenuated after the first dose. These data, combined with the previously reported results from the dose escalation phase, demonstrate a favorable safety profile of intravenous TTI-621 in over 100 patients. Intravenous administration of TTI-621, particularly in combination with rituximab, resulted in objective responses in 5 out of 18 evaluable patients with heavily pre-treated, relapsed/refractory DLBCL, and several others experienced prolonged progression-free intervals.

"The regression of local tumor lesions observed in most CTCL patients treated with intratumoral TTI-621 monotherapy provides us with a rationale to initiate a sharply focussed effort to characterize efficacy in this largely incurable disease, as well as other forms of T-cell lymphoma. Having completed the dose-escalation phase, we are now pursuing weekly dosing in the intratumoral trial with the goal of inducing systemic responses. In parallel, we continue to enroll a wide variety of T-cell lymphoma patients, including CTCL, into an expanded cohort in the intravenous TTI-621 trial," said Trillium CEO Dr. Niclas Stiernholm. "Notwithstanding the added level of complexity associated with developing combination therapies, the emerging signal in the DLBCL cohort is intriguing, especially since these patients have previously progressed after rituximab therapy." Dr. Stiernholm added, "With growing evidence supporting the tolerability of dose intensification we are now able to assess whether increasing systemic exposure of TTI-621 leads to greater anti-tumor activity in patients, including those with T-cell malignancies."

Copies of both posters will be available on Trillium’s website at the time of the presentations www.trilliumtherapeutics.com

About Cutaneous T-Cell Lymphoma (CTCL)

CTCL is a type of non-Hodgkin’s lymphoma which is characterized by localization of malignant T lymphocytes to the skin. The two most common types of CTCL are mycosis fungoides and Sézary syndrome. The disease most often involves the skin, may progress to involve lymph nodes, blood, viscera and other organs, and in select cases may become leukemic.

About Diffuse Large B-Cell Lymphoma (DLBCL)

DLBCL is the most common form of non-Hodgkin lymphoma, a cancer of white blood cells responsible for producing antibodies. While effective therapies exist for newly diagnosed DLBCL, cancer that has relapsed after treatment, or whose cancer is treatment resistant, represent an area of high unmet medical need.

On December 11, 2017 Gamida Cell, a leading cellular and immune therapeutics company, reported final results from the phase I/II trial evaluating NiCord, a product derived from cord blood stem cells, as a stand-alone graft to treat patients with high-risk hematologic malignancies (Press release, Gamida Cell, DEC 11, 2017, View Source [SID1234522566]). The study met its primary endpoint, demonstrating rapid neutrophil engraftment with manageable side effects. The company also presented preclinical data for the advancement of natural killer cells (NK cells) as an immunotherapeutic modality for patients with cancer. Both studies were presented today at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, GA.

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"We are enthusiastic about the data presented today at ASH (Free ASH Whitepaper), including the final results of our NiCord phase I/II study, which support the basis for our global phase III trial of NiCord versus standard unmanipulated cord blood transplantation (UCBT), currently enrolling patients with hematologic malignancies," said Julian Adams, Ph.D., chairman and chief executive officer of Gamida Cell. "We look forward to further evaluating the potential of NiCord to serve as the graft of choice for the thousands of patients with no matched donor in need of a transplant every year, as well as continuing to progress our other pipeline programs."

Final Data from Phase I/II Trial of NiCord.
The multicenter phase I/II study evaluated the safety and efficacy of NiCord as a stand-alone graft in 36 patients with high-risk hematologic malignancies, with a primary endpoint of time to neutrophil engraftment following transplantation. Despite varying blood cancer diagnoses and preparative conditioning regimens across patients across centers, improved results were seen in the majority of study participants treated with NiCord.

Final results of the study include the following:

Participants transplanted with NiCord had rapid and durable engraftment of neutrophils and platelets, as well as prompt immune reconstitution:
Median time to neutrophil engraftment was 11 days (95% CI: 9-13 days);
Median time to platelet engraftment was 34 days (95% CI: 32-42 days).
Results from the study participants were compared to a database of matched patients from the Center for International Blood and Marrow Transplant Research (CIBMTR). According to the CIBMTR data, patients who received UCBT had a median time to neutrophil engraftment of 21 days and a median time to platelet engraftment of 46 days.
NiCord demonstrated an acceptable safety profile, with moderate/severe chronic graft vs. host disease (cGvHD) in 9.8% of patients at one year following transplantation. By day 100, 20.2% of participants experienced grade 2-3 bacterial or grade 3 fungal infections.

"Historically, transplantation with cord blood has been limited due to slow engraftment time in patients. We are looking to address this gap, and this study demonstrated rapid and sustained engraftment in study participants by utilizing technology to expand the number of stem cord blood cells in a culture," said Mitchell Horwitz, M.D., principal investigator, co-study chair and professor of medicine at the Duke Cancer Institute. "These phase I/II data demonstrate the potential to make stem cell transplants accessible to a greater number of patients who do not have a matched donor."

Preclinical Data from NAM-NK Cell Program
Proof-of-concept data on the application of the company’s proprietary NAM technology to healthy donor natural killer cells (NK cells) as a potential immunotherapeutic approach to treating cancer were highlighted in an oral presentation.

"The use of NK cells as a modality for immunotherapy has been limited by impaired functionality of adoptively transferred NK cells in patients," said Ronit Simantov, M.D., chief medical officer at Gamida Cell. "We are encouraged by the study results, which demonstrated persistence and proliferation of NAM-NK cells in pre-clinical in vivo models and describe a reliable, scalable culture model for the expansion of functional donor NK cells aimed at clinical use."

The analysis, which combines data from multiple preclinical studies, validates the approach and is the basis for an investigator-sponsored, phase I clinical trial of NAM-NK Cells in patients with relapsed/refractory multiple myeloma or CD20-positive non-Hodgkin lymphoma.

About NiCord
NiCord, the company’s lead clinical program, is under development as a universal bone marrow transplant solution for patients with high-risk hematologic malignancies. NiCord has demonstrated improved efficacy over unmanipulated cord blood, including fewer bacterial and fungal infections and a reduction in duration of hospital stays. NiCord has been granted breakthrough status by the U.S. Food and Drug Administration, making it the first bone marrow transplant alternative to receive this designation. It has also received U.S. and EU orphan drug designation. The ongoing phase III study is evaluating NiCord as a curative treatment for patients with leukemia and lymphoma who have been indicated for an allogeneic stem cell transplant. For more information on NiCord clinical trials, please visit www.clinicaltrials.gov.

About NAM-NK Cells
Gamida Cell expanded the capabilities of its NAM technology to utilize NK cells to create an immunotherapy to treat patients with refractor blood cancers and solid tumors. Through expansion of highly functional NK cells using NAM technology, NAM-NK Cells can be used to harness the immune system to attack cancer. NAM-NK Cell is under phase I development (NCT03019666) in patients with relapsed or refractory B-cell lymphoma and multiple myeloma.