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Puma Biotechnology Announces Publication of Neratinib Abstract for the 2017 ASCO Annual Meeting

On May 17, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported the release of an abstract on its drug candidate PB272 (neratinib) that will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which will be held June 2–6, 2017, in Chicago (Press release, Puma Biotechnology, MAY 17, 2017, View Source [SID1234519193]). Abstracts are available to the public online on the ASCO (Free ASCO Whitepaper) website: www.abstract.asco.org.

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Abstract #1005, TBCRC 022: Phase II trial of neratinib + capecitabine for patients (Pts) with human epidermal growth factor receptor 2 (HER2+) breast cancer brain metastases (BCBM).

The abstract will be presented as an Oral Abstract Session: Breast Cancer–Metastatic; Saturday, June 3, 1:15–4:15 p.m. CDT, Hall D1.

Data from Clinical Studies of NewLink Genetics’ Two Distinct IDO Pathway Inhibitors to Be Presented at ASCO 2017

On May 17, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported that abstracts from two clinical studies of its IDO pathway inhibitors, indoximod and navoximod (GDC-0919), used in combination with other agents, are now available on the website of the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, NewLink Genetics, MAY 17, 2017, View Source [SID1234519192]).

An infographic accompanying this announcement is available at View Source

"The IDO pathway is a key immuno-oncology target and NewLink Genetics has two separate and distinct IDO pathway inhibitors in clinical development. Indoximod, which is wholly owned by NewLink Genetics, has a proposed differentiated mechanism within the IDO pathway and acts as a tryptophan mimetic having a direct effect on immune cells to reverse immune suppression used by cancer to protect itself. Navoximod is our direct enzymatic inhibitor of IDO and is partnered with Genentech/Roche," said Charles J. Link, Jr., M.D., Chief Executive Officer and Chief Scientific Officer of NewLink Genetics.

Indoximod in combination with the therapeutic cancer vaccine, PROVENGE

Results from a randomized, double-blind, placebo-controlled, multi-institutional Phase 2 investigator initiated study with indoximod in combination with the therapeutic cancer vaccine, PROVENGE (sipuleucel-T), for patients with metastatic castration resistant prostate cancer will be presented as a poster (Abstract number 3066) by Gautam Gopalji Jha, M.D., Adjunct Assistant Professor, Division of Hematology and Oncology, University of Minnesota, at ASCO (Free ASCO Whitepaper) in Chicago on Monday, June 5, 2017, 8:00 a.m. – 11:30 a.m. CT, titled, A phase 2 randomized, double-blind study of sipuleucel-T followed by IDO pathway inhibitor, indoximod or placebo in the treatment of patients with metastatic castration resistant prostate cancer (mCRPC).

In the study, forty-six patients were randomized into two arms to receive either twice daily oral indoximod (n=22) or placebo (n=24) for 6 months beginning the day after the third and final PROVENGE infusion. Conclusions indicate that treatment with the IDO pathway inhibitor, indoximod, post PROVENGE therapy, leads to significant improvement in radiographic progression free survival (rPFS) when compared to placebo and is well-tolerated.

Key findings presented from the study include:

Statistically significant improvement in median rPFS was 10.3 months in the treatment arm compared to 4.1 months in the placebo arm (p = 0.011)
Median Overall Survival (OS) has not yet been reached
Patients tolerated therapy with indoximod with no significant differences in adverse events between the two arms
There was no statistical difference in the primary endpoint of ELISPOT assay immune response to PA2024, the PROVENGE-related fusion protein, in the 35 of 46 patients who had clinical samples available for testing
"These data further support the hypothesis that targeting the IDO Pathway in combination with a broad backbone of treatment regimens including chemotherapy, anti-PD-1 antibodies and therapeutic vaccines across multiple indications has the potential to provide meaningful clinical benefit without compromising tolerability," commented Nicholas N. Vahanian, M.D., President and Chief Medical Officer of NewLink Genetics.

Navoximod in combination with TECENTRIQ (atezolizumab) in multiple solid tumors

Initial data from a Phase 1b dose-escalation study of navoximod in combination with TECENTRIQ for patients with locally advanced or metastatic solid tumors conducted by our partner, Genentech/Roche, will be presented in an oral presentation (Abstract number 105) by Howard A. "Skip" Burris, III, M.D., President Clinical Operations and Chief Medical Officer, Sarah Cannon Research Institute, at ASCO (Free ASCO Whitepaper) in Chicago on Sunday, June 4, 2017, 10:24 a.m. CT. The presentation is titled, A phase 1b dose-escalation study of combined inhibition of IDO1 (GDC-0919) and PD-L1 (atezolizumab) in patients with locally advanced or metastatic solid tumors.

This Phase 1b, open-label, dose-escalation study is designed to characterize safety and tolerability. Secondary objectives include identifying a maximum tolerated dose (MTD) and recommended Phase 2 dose, and evaluating pharmacokinetics, pharmacodynamics, and anti-tumor activity. Patients were given TECENTRIQ (1200 mg IV every 3 weeks) and escalating doses of navoximod (orally twice daily, for 21 days) using a standard 3+3 design. Initial results from this study (n=52, non-selected heterogeneous population during the dose escalation) found the combination was generally well-tolerated, with peripheral IDO1 modulation, and some early activity signals. Patients were previously treated with prior systemic therapies with a median number of 3 and a range of 1-9. Two patients also received prior immunotherapy.

The design of the trial includes the initial dose-escalation phase reported in this abstract, followed by disease-specific expansion cohorts (enrollment target is 305 patients) for patients with select tumor types including non-small-cell lung cancer (NSCLC), renal cell cancer (RCC), urothelial bladder cancer (UBC), triple negative breast cancer (TNBC), to further evaluate safety, response, and peripheral and tumor pharmacodynamics. Updates for this study will continue to be reported by Genentech/Roche.

Dr. Vahanian continued, "We are encouraged by the clinical profile for the combination of navoximod and atezolizumab from the first phase of this combination trial and look forward to the data for the disease-specific expansion cohorts which are currently accruing patients."

Juno Therapeutics to Present Key Clinical Data Updates on JCAR017 and JCAR014 at the 2017 American Society of Clinical Oncology Annual Meeting

On May 17, 2017 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, reported that it will present key clinical updates in partnership with its collaborators on its investigational products JCAR017 and JCAR014 at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2017 in Chicago, Illinois, June 2-6 (Press release, Juno, MAY 17, 2017, View Source [SID1234519190]).

JCAR017 and JCAR014 are chimeric antigen receptor (CAR) T cell product candidates that target CD19, a protein expressed on the surface of almost all B cell malignancies, including non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia (ALL). While the manufacturing process and final cell product differ, both product candidates utilize the 4-1BB co-stimulatory domain and use a defined cell manufacturing process, controlling the type of cells a patients receives with the goal of delivering an improved therapeutic benefit.
Insights from studies of the translational product JCAR014 are being applied to the development of JCAR017.

New data from the ongoing Phase I TRANSCEND NHL 001 trial (NCT02631044) evaluating JCAR017 in adult patients with relapsed or refractory aggressive NHL [diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL), follicular lymphoma Grade 3B, and mantle cell lymphoma (MCL)] will be presented, with increased patient numbers and longer duration of follow-up reported at two dose levels as compared to previous presentations. Updated safety data will also be presented from the ongoing Phase I trial (NCT01865617) evaluating JCAR014 in adult patients with relapsed or refractory ALL, NHL, or CLL. The JCAR014 presentation will also include data on clinical and laboratory biomarkers that may allow early identification of cytokine release syndrome (CRS) and neurotoxicity (NT).

Key data presentations at ASCO (Free ASCO Whitepaper) include:

JCAR017
CR Rates in Relapsed/Refractory (R/R) Aggressive B-NHL Treated with the CD19-Directed CAR T Cell Product JCAR017 (TRANSCEND NHL 001) (Abstract #7513)
Presenter: Jeremy Abramson, M.D., Massachusetts General Hospital
Poster Display & Location: Monday, June 5, 2017: 8:00 – 11:30 a.m. Central Time; Hall A, Poster Board #275
Poster Discussion & Location: Monday, June 5, 2017: 1:15 – 2:30 p.m. Central Time; Room E354b

JCAR014
Cytokine Release Syndrome (CRS) and Neurotoxicity (NT) after CD19-Specific Chimeric Antigen Receptor-Modified T cells (Abstract #3020)
Presenter: Kevin Hay, M.D., MSc, Fred Hutchinson Cancer Research Center
Poster Display & Location: Monday, June 5, 2017: 8:00 – 11:30 a.m. Central Time; Hall A, Poster Board #115
Poster Discussion & Location: Monday, June 5, 2017: 4:45 – 6:00 p.m. Central Time; Hall D1

About Juno’s Chimeric Antigen Receptor and T Cell Receptor Technologies
Juno’s CAR and TCR technologies genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell. JCAR014 and JCAR017 are investigational product candidates and their safety and efficacy have not been established. They are not approved by any regulatory authority.

Kite Announces Presentations on Its Lead CAR-T Therapy Development Program at the 2017 American Society of Clinical Oncology Annual Meeting

On May 17, 2017 Kite Pharma, Inc. (Nasdaq:KITE) reported new data presentations from multiple studies related to its lead investigational candidate, axicabtagene ciloleucel (also known as KTE-C19), at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL, June 2-6, 2017 (Press release, Kite Pharma, MAY 17, 2017, View Source [SID1234519191]). The full text for abstracts is available online through the ASCO (Free ASCO Whitepaper) website at View Source

“The presentations at ASCO (Free ASCO Whitepaper) continue to enhance our growing knowledge on the potential for cell therapy,” said David Chang, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Kite. “The translational insights from these data presentations are invaluable as we advance axicabtagene ciloleucel/KTE-C19 and seek to optimize treatment, not only in NHL, but also across a broad range of hematologic malignancies.”

Poster Discussion:

Clinical and biologic covariates of outcomes in ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (r-NHL)

Abstract #7512
Session: Poster Session: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Poster Board #274
Session Time/Location: Monday, June 5, 2017: 8:00-11:30 AM CDT, Hall A
Poster Discussion Session Time/Location: Monday, June 5, 2017: 1:15-2:30 PM CDT, E354b
Presenter: Frederick L. Locke, M.D., Moffitt Cancer Center, Tampa, FL
Poster Presentations

Updated results from ZUMA-3, a phase 1/2 study of KTE-C19 chimeric antigen receptor (CAR) T cell therapy, in adults with high-burden relapsed/refractory acute lymphoblastic leukemia (R/R ALL)

Abstract #3024
Session: Poster Session: Developmental Therapeutics – Immunotherapy
Poster Board #119
Session Time/Location: Monday, June 5, 2017: 8:00-11:30 AM CDT, Hall A
Presenter: Bijal D. Shah, M.D., Moffitt Cancer Center, Tampa, FL
Product characteristics associated with in vivo expansion of anti-CD19 CAR T cells in patients treated with axicabtagene ciloleucel (axi-cel)

Abstract #3023
Session: Poster Session: Developmental Therapeutics – Immunotherapy
Poster Board #118
Session Time/Location: Monday, June 5, 2017: 8:00-11:30 AM CDT, Hall A
Presenter: Frederick L. Locke, M.D., Moffitt Cancer Center, Tampa, FL
Characterization of anti-CD19 chimeric antigen receptor (CAR) T cell-mediated tumor microenvironment immune gene profile in a multicenter trial (ZUMA-1) with axicabtagene ciloleucel (axi-cel, KTE-C19)

Abstract #3025
Session: Poster Session: Developmental Therapeutics – Immunotherapy
Poster Board #120
Session Time/Location: Monday, June 5, 2017: 8:00-11:30 AM CDT, Hall A
Presenter: Jerome Galon, Ph.D., Laboratory of Integrative Cancer Immunology, INSERM
ZUMA-6: Phase 1-2 multicenter study evaluating safety and efficacy of axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab in patients with refractory diffuse large B-cell lymphoma (DLBCL)

Abstract #TPS7572
Session: Trials in Progress Poster Session: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Poster Board #331a
Session Time/Location: Monday, June 5, 2017: 8:00-11:30 AM CDT, Hall A
Presenter: Frederick L. Locke, M.D., Moffitt Cancer Center, Tampa, FL
Online Publication

Total 1-year cost of diffuse large B-cell lymphoma (DLBCL) beyond first-line (1L) therapy: A retrospective cohort analysis

Abstract # e18333
Senior Author: Anna Purdum, PharmD, M.S., Kite Pharma
About axicabtagene ciloleucel

Kite’s lead product candidate, axicabtagene ciloleucel, previously known as KTE-C19, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

New Data for Presentation at ASCO 2017 Reinforce Clinical Profile of Epacadostat in Combination with Keytruda® (pembrolizumab)

On May 17, 2017 Incyte Corporation (Nasdaq:INCY) reported the publication of new data from the ongoing ECHO-202 trial, evaluating epacadostat, Incyte’s selective IDO1 enzyme inhibitor, in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Incyte, MAY 17, 2017, View Source [SID1234519189]).

Abstracts published online by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in advance of its annual meeting in Chicago, Illinois, June 2-6, 2017 include ECHO-202 Phase 1/2 efficacy and safety data from the following cohorts: non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), and ovarian cancer (OVC). Pooled Phase 2 safety data across cohorts were also released today.

"We are very pleased to share these new data for epacadostat in combination with pembrolizumab. The combination is well-tolerated and preliminary efficacy outcomes for these cohorts demonstrate encouraging clinical activity, both within and across tumor types, which compares favorably to contemporary data in the second-line setting. These data, including updated data which will be presented at ASCO (Free ASCO Whitepaper) next month, supported the recently-announced progression of the epacadostat and pembrolizumab combination into pivotal trials in NSCLC, RCC, bladder cancer and SCCHN," said Steven Stein, M.D., Chief Medical Officer, Incyte.

ECHO-202 abstract data for the tumor types entering Phase 3 (data cut as of October 29, 2016) include:

n/N
(%)
NSCLC UC SCCHN RCC
All pts
0-2 prior lines of
therapy for advanced
disease
All pts
Prior Lines of
Treatment
All pts
Prior Lines of
Treatment
All pts
Prior Lines of
Treatment
Total TPS ≥50% TPS <50% Total 0-1 Total 1-2 ≥3 Total 0-1 ≥2
ORR 14/40
(35) 3/7
(43) 6/17
(35) 13/37
(35) 10/27
(37)
11/36
(31)

10/29
(34)

1/7
(14)

9/30
(30)

9/19
(47)
0/11
(0)
all PR all PR all PR all PR all PR 2 CR,
9 PR 2 CR,
8 PR 1 PR 1 CR,
8 PR 1 CR,
8 PR -
DCR 24/40
(60) 4/7
(57) 9/17
(53) 21/37
(57) 17/27
(63) 21/36
(58)
18/29
(62)
3/7
(43) 15/30
(50) 11/19
(58) 4/11
(36)

DoR
12/14 responses ongoing
range 1+ – 519 days

12/13 responses ongoing
range 1+ – 652+ days

9/11 responses ongoing
range 1+ – 563+ days

9/9 responses ongoing
range 1+ – 372+ days

In a pooled analysis evaluating 244 patients in the ECHO-202 Phase 2 safety population (abstract #3012), treatment-related adverse events (TRAEs) that occurred in ≥5 percent of patients, included fatigue (23 percent); rash (16 percent); diarrhea and nausea (7 percent each); increased alanine aminotransferase, increased aspartate aminotransferase, and pruritus (6 percent each); and pyrexia (5 percent). A total of 37 patients (15 percent) experienced Grade ≥3 TRAEs; the most common of which were increased lipase (asymptomatic) and rash (3 percent each). TRAEs led to discontinuation of treatment in 3 percent of study patients.
These abstracts, including data for TNBC and OVC (abstract #1103), were made available today on the ASCO (Free ASCO Whitepaper) website at www.asco.org.

About ECHO-202 (KEYNOTE-037)
The ECHO-202 study (NCT02178722) is evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 inhibitor, in combination with pembrolizumab. Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded from this trial. Enrollment is complete for the Phase 1 dose escalation (epacadostat 25, 50, 100 mg BID + pembrolizumab 2 mg/kg IV Q3W and epacadostat 300 mg BID + pembrolizumab 200 mg IV Q3W) and Phase 1 dose expansion (epacadostat 50, 100, and 300 mg BID + pembrolizumab 200 mg IV Q3W) portions of the trial. For more information about ECHO-202, visit View Source

About ECHO
The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors collectively plan to enroll over 900 patients in a broad range of solid tumor types as well as hematological malignancies. ECHO-301 (NCT02752074), a Phase 3 randomized, double-blind, placebo-controlled study investigating KEYTRUDA in combination with epacadostat or placebo for the treatment of patients with unresectable or metastatic melanoma, is also underway. For more information about the ECHO clinical trial program, visit www.ECHOClinicalTrials.com.

About Epacadostat (INCB024360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is a first-in-class, highly potent and selective oral inhibitor of the IDO1 enzyme that regulates the tumor immune microenvironment, thereby restoring effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor pembrolizumab improved response rates compared with studies of the immune checkpoint inhibitors alone.