1stOncology™: Cancer Intelligence Service – Page 14366 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

ATARA BIOTHERAPEUTICS ANNOUNCES THIRD QUARTER 2018 FINANCIAL RESULTS AND RECENT OPERATIONAL PROGRESS

On November 6, 2018 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported financial results for the third quarter of 2018 and recent operational progress (Press release, Atara Biotherapeutics, NOV 6, 2018, View Source [SID1234530798]).

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!

"We made important progress in the third quarter advancing our off-the-shelf, allogeneic T-cell immunotherapy pipeline," said Isaac Ciechanover, M.D., Chief Executive Officer and President of Atara Biotherapeutics. "We recently announced a strategic collaboration with Moffitt Cancer Center to expand our next-generation CAR T immunotherapy pipeline and initiated a Phase 1/2 clinical study of tab-cel in combination with Merck’s KEYTRUDA for patients with EBV-associated nasopharyngeal carcinoma. This is an exciting period for Atara and we look forward to updating you on additional pipeline results at the ASH (Free ASH Whitepaper) and ESMO (Free ESMO Whitepaper) IO scientific congresses in December."

Atara continues to advance its tab-cel (tabelecleucel) Phase 3 studies for patients with Epstein-Barr virus associated post-transplant lymphoproliferative disorder (EBV+ PTLD) and anticipates initial tab‑cel Phase 3 results in the first half of 2019. The Company is in ongoing discussions with the European Medicines Agency (EMA) and U.S. Food & Drug Administration (FDA) regarding the development and regulatory paths for tab‑cel based on its experience conducting the Phase 3 studies in patients with this life-threatening condition. The Company plans to share initial Phase 3 clinical results as well as observed EBV+ PTLD incidence with these agencies. The outcomes of both regulatory discussions are expected in the first half of 2019, and Atara now plans to submit a tab‑cel EU conditional marketing authorization (CMA) application in the second half of 2019.

Atara continues to build its pipeline and operational capabilities as well as prepare for the launch of its first commercial product. Initial results from the off-the-shelf, allogeneic ATA188 multiple sclerosis program are anticipated in the first half of 2019. In addition, the Company is rapidly advancing its next-generation chimeric antigen receptor T-cell (CAR T) pipeline across multiple therapeutic areas and expects to highlight results at upcoming events.

Recent Highlights and Anticipated Upcoming Milestones

Tab-cel (tabelecleucel)

Two Phase 3 clinical studies are ongoing (MATCH and ALLELE) to evaluate tab-cel (tabelecleucel) for patients with EBV+ PTLD who have failed rituximab following hematopoietic cell transplant (HCT) or solid organ transplant (SOT).
– Expanded MATCH and ALLELE study sites with 26 locations available for enrollment in the United States and Australia with additional sites expected to open in the United States and other geographies.

Initiated a Phase 1/2 clinical study of tab-cel in combination with Merck’s anti-PD-1 (programmed death receptor-1) therapy, KEYTRUDA (pembrolizumab), in patients with platinum-resistant or recurrent EBV-associated nasopharyngeal carcinoma (NPC).

Scheduled to present new tab-cel efficacy and safety results in patients with EBV-associated leiomyosarcoma (EBV+ LMS) solid tumors at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress in December 2018.
60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting

Announced eight abstracts highlighting robust off-the-shelf, allogeneic T-cell immunotherapy pipeline and next-generation CAR T technologies to be presented at the 60th ASH (Free ASH Whitepaper) Annual Meeting in December 2018.
– Moffitt Cancer Center collaborators to present next-generation CAR T technology that increases T cell persistence and decreases exhaustion.
– Memorial Sloan Kettering (MSK) collaborators to present tab‑cel Phase 2 clinical results for patients with EBV+ PTLD involving the central nervous system (CNS).
– Current PTLD patient health outcomes and treatment patterns are described in additional ASH (Free ASH Whitepaper) abstracts.
Next-Generation CAR T Development Pipeline

Announced a strategic collaboration with Moffitt Cancer Center to develop multi-targeted CAR T immunotherapies for patients with AML and B cell malignancies.
– Along with prior CAR T collaboration with MSK, furthers Atara’s strategy to develop next‑generation CAR T immunotherapies across multiple therapeutic areas and leverage the Company’s off-the-shelf, allogeneic T-cell immunotherapy platform.
– Research supporting the novel CAR T co-stimulatory domain findings were recently published in the September 2018 issue of the Journal of Clinical Investigation.
– CAR T preclinical activities ongoing, with initial IND expected Q4 2019 to Q1 2020.

Hosting CAR T Breakfast Teach-In on November 29, 2018 in New York, NY focused on Atara’s next-generation CAR T immunotherapy pipeline for patients with hematologic and solid tumors, autoimmune and infectious diseases as well as off-the-shelf, allogeneic CAR T development using EBV-specific T cell platform.
– Featured experts: Michel Sadelain, M.D., Ph.D., MSK and Marco Davila, M.D., Ph.D., Moffitt Cancer Center.
ATA188 & ATA190 for Multiple Sclerosis (MS)

A Phase 1 clinical study to evaluate off-the-shelf, allogeneic ATA188 in patients with progressive MS is underway across clinical sites in the United States and Australia.
– Initial results from the ongoing study are expected in the first half of 2019.

Plan to initiate a randomized autologous ATA190 study in progressive MS patients in 2019.
Other Pipeline

Recent positive published results support Atara’s continued development of ATA621, targeting both JC and BK viruses for patients with progressive multifocal leukoencephalopathy (PML). The Company is currently conducting IND enabling manufacturing process development for this program.
Corporate

Strengthened the Company’s Board of Directors with the appointment of Roy Baynes, M.D., Ph.D. Dr. Baynes currently serves as Senior Vice President Global Clinical Development and Chief Medical Officer at Merck Research Laboratories.

Additional appointments include the promotion of Manher (AJ) Joshi, M.D., to Chief Medical Officer, the appointment of Renu Vaish as Atara’s Senior Vice President, Global Regulatory Affairs, as well as Jose Vidal’s appointment as Atara’s Senior Vice President, Head of GMP Quality and Process Sciences.

Continued to increase manufacturing activities at Atara T Cell Operations & Manufacturing (ATOM) facility with completion of licensure to support clinical production expected in 2019.
Third Quarter 2018 Financial Results

Cash, cash equivalents and short-term investments as of September 30, 2018 totaled $364.5 million, which the Company believes will fund planned operations to mid-2020.
The Company reported net losses of $58.4 million, or $1.29 per share, for the third quarter of 2018, as compared to $31.1 million, or $1.02 per share, for the same period in 2017.
In the third quarters of 2018 and 2017, total operating expenses of $60.2 million and $31.7 million included non-cash expenses of $10.4 million and $6.3 million, respectively.
Research and development expenses were $43.4 million for the third quarter of 2018, as compared to $20.6 million for the same period in 2017. The increase in the third quarter of 2018 was due to costs associated with the Company’s continuing expansion of research and development activities, including:
– clinical trial, manufacturing and outside service costs related to the two Phase 3 clinical trials of tab-cel in patients with EBV+ PTLD and the Phase 1 clinical trial of allogeneic ATA188 in patients with MS, and
– higher employee-related and overhead costs from increased headcount and operations.
Research and development expenses include $4.7 million and $2.1 million of non-cash stock-based compensation expenses in the third quarters of 2018 and 2017, respectively.
General and administrative expenses were $16.9 million for the third quarter of 2018, as compared to $11.1 million for the same period in 2017. The increase in the third quarter of 2018 was primarily due to increases in professional services costs and employee-related costs from increased headcount to support the Company’s expanding operations. General and administrative expenses include $4.6 million and $3.9 million of non-cash stock-based compensation expenses in the third quarters of 2018 and 2017, respectively.

OncoSec Reports Preliminary Data from
KEYNOTE-695 Phase 2b RegistrationDirected Clinical Trial of TAVO™ in Combination with KEYTRUDA® for
Metastatic Melanoma at Society for
Immunotherapy of Cancer’s 33rd Annual
Meeting

On November 6, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing novel cancer immunotherapies based on its proprietary technology generating sustained intratumoral IL-12 levels, today reported preliminary data from KEYNOTE-695, a global, multicenter Phase 2b, open-label trial of intratumoral delivery of TAVO (tavokinogene telseplasmid / IL-12) with intravenous KEYTRUDA (pembrolizumab) in patients with unresectable, advanced melanoma (Press release, OncoSec Medical, NOV 6, 2018, View Source [SID1234530797]). Eligible patients had refractory, locally advanced or metastatic disease defined as unresectable Stage III/IV metastatic melanoma that had definitively progressed on a full-course of anti-PD-1 treatment with KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab).

As of September 1, 2018, 21 patients had been enrolled in the study. Out of the 21 patients, nine patients had completed 12 weeks of treatment and reached the first tumor evaluation point at approximately 12 weeks, while the remaining 12 patients had not yet reached the first tumor evaluation. All nine patients were previously treated and definitively progressed on anti-PD-1 therapies with 56% (5/9) having had more than one prior line of therapy. All enrolled patients had exceedingly low frequencies of intratumoral CD8+ peCTL (PD-1+/CTLA-4+) at screening with a notable increase in TIL density following treatment.

Two of the nine patients experienced a partial response and one patient had stable disease (22% BORR and 33% DCR) by RECIST v1.1. Tumor responses were noted in both treated and untreated lesions. Of the two responding patients, both had multiple prior rounds of anti-PD-1 therapy, with no response, and one had also progressed after 4
cycles of OPDIVO and YERVOY (ipilimumab), an FDA-approved anti-CTLA4 / anti-PD1 antibody combination. Tumor responses were associated with treatment-related upregulation of immune-based transcripts in the tumor microenvironment, as well as increased frequencies of intratumoral T cells within three weeks of therapy.

"There is currently no approved therapy for the KEYNOTE-695 patient population. A 10% response rate is considered meaningful in this cohort, since this is about what we expect with additional chemotherapy, however, such responses lack durability. The preliminary tumor responses (22% BORR and 33% DCR) and supporting immune data observed here for the first time are important," said Adil Daud, MD, HS Clinical Professor, Department of
Medicine (Hematology/Oncology), UCSF; Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center.

KEYNOTE-695 enrollment criteria with respect to anti-PD-1 checkpoint failure is highly restrictive. In order to be considered an anti-PD-1 checkpoint failure, all patients must have Stage III/IV metastatic melanoma progressive disease after at least four prior cycles of either KEYTRUDA or OPDIVO. Disease progression is determined according to RECIST v1.1, measured by radiologic assessment, with confirmation of progression by second assessment. All patients must receive their first TAVO / KEYTRUDA combination treatment within 24 weeks of the last dose of an FDA approved anti-PD-1 therapy, with no intervening therapies between such failure and KEYNOTE695 enrollment. Patients that were BRAF eligible must have received and progressed
following BRAF treatment.

"Although several clinical studies have reported late-stage melanoma data in anti-PD-1 failures, such failures are inconsistently defined. This is a critical point," continued Dr. Daud. "Since patients in KEYNOTE-695 have unequivocally failed approved anti-PD-1 therapies, these preliminary data, viewed in this context, carry weight."
TAVO was well-tolerated, with Grade 1 adverse advents associated with injection site or procedural pain. One TAVO related Grade 3 SAE of cellulitis was reported and resolved.

KEYNOTE-695 is a registration-enabled clinical trial. In order to be eligible for accelerated approval, a product candidate must treat a serious condition and provide a meaningful advantage over available therapies. In early 2017 and prior to the commencement of the study, the Company reviewed the patient inclusion criteria with FDA so that KEYNOTE695 could be submitted to FDA for accelerated approval. KEYNOTE-695 is expected to
be completed in 2019. Based on the outcome of the study and feedback from FDA, the Company plans to file for accelerated approval by end of 2019 or early 2020.

TAVO has received both Orphan Drug and Fast-Track Designation by the U.S. Food & Drug Administration.

Advaxis To Present Poster Entitled “Natural Killer (NK) Cells Orchestrate The Antitumor Activities Of Listeria Monocytogenes (Lm)-Based Immunotherapy” At Society For Immunotherapy Of Cancer Annual Meeting

On November 6, 2018 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, announces a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Advaxis, NOV 6, 2018, View Source [SID1234530796]). The poster, entitled "Natural killer (NK) cells orchestrate the antitumor activities of Listeria monocytogenes (Lm)-based immunotherapy," evaluated the impact of Lm-based immunotherapy on the activation of NK cells in a murine model of human papillomavirus (HPV)-associated tumors.

Poster Number P520 will be presented by Sandy Hayes, Ph.D., Sr. Director, Research – BioMarkers and Immune Monitoring, on Saturday, November 10, 2018 from 12:20 – 1:50 p.m. and 7:00 – 8:30 p.m. Eastern time at the 2018 SITC (Free SITC Whitepaper) 33rd annual meeting at the Walter E. Washington Convention Center in Washington, D.C.

"The results demonstrate that AXAL can induce changes in the tumor microenvironment that promote NK cell activation, establish cross-talk between dendritic cells (DC cells), NK cells, and can facilitate trafficking of tumor antigen-specific T cells into the tumor core which we believe contribute to the antitumor activity of AXAL," said Robert G. Petit, Ph.D., Executive Vice President and Chief Scientific Officer of Advaxis. "The critical role of NK cells and NK-DC crosstalk is part of the broad-based immunologic profile associated with Advaxis Lm vectors and their favorable alteration of the microenvironment for immunotherapy of solid tumors."

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack that is currently in Phase 3 clinical testing. In a Phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38% in 50 patients. This is a 52% improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors.

Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications.

Verastem Oncology Announces Presentation of Preclinical Data Supporting Dual PI3K-delta and PI3K-gamma Inhibition in Combination with Immunotherapy at the Society for Immunotherapy of Cancer’s 33rd Annual Meeting

On November 6, 2018 Verastem, Inc. (Nasdaq: VSTM) (Verastem Oncology or the Company), focused on developing and commercializing medicines to improve the survival and quality of life of cancer patients, reported a poster presentation of preclinical data by Jonathan Pachter, Ph.D., the Company’s Chief Scientific Officer, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting being held November 7-11, 2018, in Washington, D.C (Press release, Verastem, NOV 6, 2018, View Source;p=irol-newsArticle&ID=2375552 [SID1234530795]).

"We have assessed the activity of duvelisib, our orally-administered dual inhibitor of PI3K-delta and PI3K-gamma, in combination with either immune checkpoint or co-stimulatory antibodies in syngeneic antitumor models," said Dr. Pachter. "Results to be presented at SITC (Free SITC Whitepaper)’s 33rd Annual Meeting demonstrated that duvelisib shows strong anti-tumor synergy with PD-1 or OX40 antibodies. As a dual PI3K-delta/gamma inhibitor, duvelisib was found to reduce both immunosuppressive Tregs and myeloid cells in tumors more strongly than PI3K-delta, or PI3K-gamma only inhibitors, suggesting that it could be a highly-differentiated PI3K inhibitor for combination with immuno-oncology therapeutics. These preclinical results support clinical investigation of duvelisib in combination with immunotherapies for treatment of patients with hematological or solid tumor malignancies."

Details for the poster presentation are as follows:

Title: Synergistic efficacy of duvelisib with checkpoint or co-stimulatory antibodies in a B cell lymphoma model: Advantages of dual inhibition of PI3K-delta and PI3K-gamma

Abstract poster number: P373

Date and time: Friday, November 9, 2018 from 12:45-2:15 PM and 6:30 – 8:00 PM ET

Location: Hall E

A copy of the poster will be available here following its presentation at the meeting

Alkermes Presents New Data on ALKS 4230 at Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting

On November 6, 2018 Alkermes plc (Nasdaq: ALKS) reported the presentation of three abstracts at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in Washington, D.C., Nov. 9-11, 2018 (Press release, Alkermes, NOV 6, 2018, View Source;p=irol-newsArticle&ID=2375550 [SID1234530794]). Initial clinical data from the ongoing monotherapy dose-escalation stage of the phase 1 study for ALKS 4230, the company’s immuno-oncology drug candidate, will be presented for the first time. ALKS 4230 is a novel, engineered fusion protein designed to selectively activate tumor-killing immune cells while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex.

"The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while overcoming its limitations. These initial data from our phase 1 study demonstrate the unique mechanism of ALKS 4230, with dose-dependent pharmacodynamic effects on circulating natural killer cells and CD8+ T cells and minimal and non-dose dependent effects on immunosuppressive regulatory T cells," said Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "Based on these data from our initial monotherapy dose-escalation cohorts, we’ve accelerated the development program to include evaluation of ALKS 4230 in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA). As we continue to pursue the optimal dose of ALKS 4230 in the monotherapy setting, we are also eager to explore other regimens that may provide greater dosing flexibility for patients, and plan to initiate a study for subcutaneous dosing in early 2019."

Details of the poster presentations at SITC (Free SITC Whitepaper) are as follows:

Abstract Poster #P423: "Safety, Pharmacokinetics and Pharmacodynamic Effects of ALKS 4230 in Patients With Advanced Solid Tumors From the Ongoing Dose Escalation Portion of a First-in-Human (FIH) Study," will be presented by Ulka N. Vaishampayan, M.D., Barbara Ann Karmanos Cancer Institute
ALKS 4230 was assessed in 24 patients with refractory solid tumors at doses ranging from 0.1 µg/kg/day to 3 µg/kg/day as part of the ongoing phase 1 study.
Treatment with ALKS 4230 resulted in a dose-dependent increase in circulating natural killer (NK) cells and CD8+ T cells with a near 4-fold and 2-fold expansion, respectively, at 3 µg/kg/day, and minimal, non-dose-dependent change in regulatory T (Treg) cells.
Fever and chills were the most common treatment-related adverse events (AEs) for ALKS 4230.
These data support the rationale for assessing ALKS 4230 at the 3 µg/kg/day dose in combination with pembrolizumab, as well as for continued dose escalation in the monotherapy setting.
Abstract Poster #P425: "Pharmacokinetics and Pharmacodynamic Effects of ALKS 4230, an Investigational Immunotherapeutic Agent, in Cynomolgus Monkeys After Intravenous and Subcutaneous Administration," will be presented by Lei Sun, Ph.D., Alkermes, Inc.
Data from two non-human primate studies demonstrated that subcutaneous administration of ALKS 4230 can achieve similar total systemic exposure of ALKS 4230 compared to intravenous administration, yet with less frequent dosing and a lower Cmax, leading to similar expansion of total CD8+ T cell and NK cell populations.
These data support further clinical evaluation of subcutaneous administration of
ALKS 4230 as an alternative to intravenous dosing.
Abstract Poster #P123: "Peripheral Blood Lymphocyte Responses in Patients With Renal Cell Carcinoma Treated With High-Dose Interleukin-2," will be presented by Wenxin Xu, M.D., Beth Israel Deaconess Medical Center
Consistent with the known biological activities of IL-2, administration of high-dose IL-2 resulted in an approximate 2-fold expansion of circulating cytotoxic effector CD8+ T cells and NK cells and an approximate 4-fold expansion of circulating Treg cells.
These data provide quantitative measures of the expansion of cytotoxic effectors such as CD8+ T cells and NK cells relative to Treg cells for high-dose IL-2, and may be useful in the future for evaluating possible differences in immune response to newer formulations of
IL-2.
Posters will be on display both Friday, Nov. 9 and Saturday, Nov. 10 beginning at 8:00 a.m. ET in Hall E of the Walter E. Washington Convention Center. For more information, including a complete list of abstracts, please visit the SITC (Free SITC Whitepaper) website at View Source

About the Phase 1 Study for ALKS 4230
The phase 1 study for ALKS 4230 includes three distinct stages: the ongoing monotherapy dose-escalation stage, the planned monotherapy dose-expansion stage and the recently initiated combination therapy stage with pembrolizumab. The dose-escalation stage is designed to determine a maximum tolerated dose of ALKS 4230 in a monotherapy setting and to identify the optimal dose range of ALKS 4230 based on measures of immunological-pharmacodynamic effects. Upon completion of the dose-escalation stage, Alkermes expects to initiate the monotherapy dose-expansion stage in patients with renal cell carcinoma or melanoma. The combination therapy stage of the phase 1 study will assess the safety profile and anti-tumor activity of ALKS 4230 with pembrolizumab in patients with select advanced solid tumors. This combination therapy stage will be run independent of, and concurrently with, the monotherapy dose-escalation and dose-expansion stages of the trial.

Anti-tumor response and duration of response assessments in the dose-expansion and combination stages of the phase 1 study will be based on investigator-assessed, immune-related response criteria(irRC) and independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.

About ALKS 4230
ALKS 4230 is a novel, engineered fusion protein designed to selectively activate tumor-killing immune cells while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while overcoming its limitations.