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Updated Data for Indoximod Plus KEYTRUDA® (pembrolizumab) Demonstrate Improvement of Response Rate for Patients with Advanced Melanoma

On September 7, 2017 NewLink Genetics Corporation (NASDAQ: NLNK) reported updated data from the ongoing Phase 2 NLG2103 study of indoximod, NewLink Genetics’ IDO pathway inhibitor, in combination with the PD-1 pathway inhibitor, KEYTRUDA (pembrolizumab) (Press release, NewLink Genetics, SEP 7, 2017, View Source [SID1234520412]). These data will be highlighted in an oral presentation at the Third International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in Frankfurt/Mainz, Germany, on September 9, 2017 by Yousef Zakharia, M.D., Assistant Professor of Medicine, Division of Hematology, Oncology and Blood & Marrow Transplantation at the University of Iowa and Holden Comprehensive Cancer Center.

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The presentation entitled, "Combined Inhibition of the IDO and PD-1 Pathways Improves the Response Rate for Patients with Advanced Melanoma", showed an improvement over previously reported results presented at the AACR (Free AACR Whitepaper) Annual Meeting 2017 for both the Complete Response rate (CR) and the Overall Response Rate (ORR) for patients1 who received indoximod plus pembrolizumab. Evaluable patients were defined as those having at least one on-treatment imaging study.

Key findings in the updated data reported today:

Improvement in Complete Response (CR) to 20% (10/51 patients) compared to CR of 12% (6/51 patients)
The Progression-Free Survival (PFS) by RECIST criteria was 56% at one year with median PFS (mPFS) of 12.9 months
"We are encouraged by the progression-free survival and the improvement in complete responses observed in the trial," said Charles J. Link, Jr., M.D., Chairman, Chief Executive Officer, and Chief Scientific Officer. "The updated data further support our decision to initiate a pivotal trial for patients with advanced melanoma."

Indoximod plus Pembrolizumab Data from Phase 2 Trial in Advanced Melanoma
n1 = 51 patients n (%)
ORR 31 (61)
CR 10 (20)
PR 21 (41)
SD 10 (20)
DCR 41 (80)
PD 10 (20)
mPFS (months) 12.9
PFS at 12 months 56%
overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD), disease control
rate (DCR), progressive disease (PD), median progression-free survival (mPFS), progression-free survival (PFS)
1 Update includes only those patients with cutaneous, mucosal and melanoma of unknown primary origin.
Data as presented at Third International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper)
Indoximod in combination with pembrolizumab was well-tolerated. The most common all-grade adverse events were fatigue, headache, and nausea. Three patients experienced grade 3 serious adverse events (SAE) possibly attributed to indoximod. Three patients experienced SAEs that led to discontinuation of treatment. There were no treatment related deaths.

Pivotal Trial of Indoximod in Advanced Melanoma to Include Both PD-1 Inhibitors, KEYTRUDA (pembrolizumab) and OPDIVO (nivolumab)

The pivotal trial has been designed as a large-scale (600 patients) trial in Stage III unresectable and metastatic stage IV melanoma. The trial will have a one to one randomization between indoximod plus KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab) compared to single agent PD-1 inhibitor. The co-primary endpoints of the study are PFS by RECIST criteria and Overall Survival (OS).

"Our team is excited to move forward with this pivotal trial," said Eugene Kennedy, M.D., Vice President of Clinical and Medical Affairs. "We believe that allowing physicians the choice of either pembrolizumab or nivolumab accurately reflects current clinical care and should aid in enrolling the trial by the end of 2018."

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is one of the key immuno-oncology targets involved in regulating the tumor microenvironment and immune escape.

NewLink Genetics is currently evaluating indoximod in multiple combination studies for patients with various types of cancer including melanoma, acute myeloid leukemia, pancreatic cancer and prostate cancer.

Kura Oncology Announces Positive Phase 2 Study for Tipifarnib in HRAS Mutant Head and Neck Cancer

On September 7, 2017 Kura Oncology, Inc., (Nasdaq:KURA) a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported positive topline results from a Phase 2 trial for its lead product candidate, tipifarnib, in patients with HRAS mutant relapsed or refractory squamous cell carcinomas of the head and neck (HNSCC) (Press release, Kura Oncology, SEP 7, 2017, View Source [SID1234520411]). The Phase 2 trial achieved its primary endpoint prior to the completion of enrollment.

The trial protocol requires four confirmed, partial responses, per RECIST 1.1 criteria, out of 18 patients to meet its primary endpoint. Four confirmed, partial responses and two patients with disease stabilization have been observed among the first six evaluable HNSCC patients enrolled in the trial. In addition, objective responses greater than one year in duration have already been observed in two patients. All patients joined the study upon progression on prior therapy, including chemotherapy, cetuximab or immune therapy. Kura will continue to enroll HRAS mutant HNSCC patients and plans to present data from the study at an upcoming scientific or medical conference.

"We have observed rapid and, in some cases, dramatic responses in patients with relapsed and/or refractory HNSCC who do not appear to benefit from other therapies," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer of Kura Oncology. "Based on these very encouraging results, we are exploring available options to advance the development of tipifarnib in this patient population as quickly as possible."

About HRAS Mutant HNSCC

Head and neck cancer is one of the leading causes of cancer-related deaths worldwide, with squamous cell carcinomas accounting for most head and neck cancers. Response rates for the three agents approved for treatment of HNSCC in the second line, including cetuximab and immune therapy agents, are in the range of 13-16%, and median overall survival is up to 7.5 months. HRAS is a proto-oncogene that has been implicated in the development and progression of HNSCC and has been established to be uniquely farnesylated.

Iovance Biotherapeutics Enters into a Research Collaboration Focused on Hematologic Malignancies with The Ohio State University Comprehensive Cancer Center

On September 7, 2017 Iovance Biotherapeutics, Inc. (NASDAQ:IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that it has entered into a preclinical research collaboration with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) focused on TIL, marrow-infiltrating lymphocyte (MIL) and peripheral blood-associated lymphocyte technologies (Press release, Iovance Biotherapeutics, SEP 7, 2017, View Source [SID1234520410]).

The collaboration will initially focus on hematologic malignancies in areas of poor prognostic cancers with high unmet medical need, which include acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). The collaboration will be co-led by Iovance researchers and by Dr. John Byrd, D. Warren Brown Chair of Leukemia Research, Distinguished University Professor of Medicine, Medicinal Chemistry and Veterinary Biosciences at the OSUCCC – James.

"We are very pleased to collaborate with the OSUCCC – James and Dr. Byrd, who brings an impressive track record and expertise in the preclinical and clinical development of ground-breaking hematological therapies," said Maria Fardis, Ph.D., MBA, President and Chief Executive Officer of Iovance Biotherapeutics. "Our initial internal work in developing TIL in hematologic malignancies will be presented at the upcoming ESMO (Free ESMO Whitepaper) 2017 Congress and that work, along with our collaboration with the OSUCCC – James, shows our continued efforts in exploring the utilization of TIL therapy in hematological oncology indications, in addition to our ongoing clinical work in solid tumor indications."

"TIL directed therapy is an exciting novel application to both AML and CLL and our research team at the OSUCCC – James is excited to be part of this collaborative research to explore this new treatment approach," said Dr. Byrd.

Ignyta Announces Presentation of New Phase 1B Clinical Data on RXDX-105 in RET Fusion-Positive NSCLC at ESMO 2017 Congress

On September 7, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported that new data on RXDX-105 – a VEGFR-sparing, potent RET inhibitor – will be presented in a late-breaking proffered paper session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in Madrid, Spain on Sunday, September 10 at 5:15 p.m. Central European time (Press release, Ignyta, SEP 7, 2017, View Source [SID1234520408]).

A conference call and live webcast will be held on September 11, 2017, at 5:00 a.m. Pacific time (8:00 a.m. Eastern time) to discuss highlights of the data presented and to provide a pipeline review, including lead product candidate entrectinib—an orally bioavailable, CNS-active tyrosine kinase inhibitor focused on targeting tumors that harbor NTRK fusions or ROS1 fusions, currently being studied in a registration-enabling Phase 2 clinical trial known as STARTRK-2.

To participate in the conference call, please dial (800) 930-1344 (U.S.) or (719) 457-2642 (international) and provide Conference ID 6430774. To access the live webcast, go to View Source." target="_blank" title="View Source." rel="nofollow">View Source

A replay of the presentation will be available shortly after the conclusion of the live call in the Investors section of the company’s website at View Source, and will be archived and available at that site for 14 days.

Roche announces progress in biomarker science in cancer immunotherapy at the European Society for Medical Oncology Congress

On September 7, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the first data on a novel blood-based assay, co-developed with Foundation Medicine (NASDAQ: FMI), will be presented during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress from 8-12 September 2017 in Madrid, Spain (Press release, Hoffmann-La Roche, SEP 7, 2017, View Source [SID1234520407]).1 These data have been generated as part of a broad, ongoing effort to advance the personalisation of cancer immunotherapy by delivering treatment options tailored to the specific immune biology associated with a person’s tumour. In pursuit of this goal, Roche is currently developing 20 cancer immunotherapy medicines across 9 types of cancer and in more than 50 combinations with other medicines. Roche is committed to advancing the science of cancer immunotherapy and exploring multiple biomarker approaches including PD-L1 immunohistochemistry, tumour gene expression, RNA sequencing and tumour mutational burden (TMB).2

New data presented at ESMO (Free ESMO Whitepaper) demonstrates for the first time that a blood-based TMB test (bTMB) can measure TMB with a high degree of precision and accuracy.1 TMB is a quantitative clinical marker that measures the number of mutations within a tumour genome. TMB has been found to be an indicator of likelihood of progression-free survival (PFS) benefit from immunotherapies when used alone (monotherapy) in patients with non-small cell lung cancer (NSCLC).3,4 Until now, TMB could only be measured using a tumour biopsy. By using this blood-based testing approach, it may be possible to extend TMB testing to more patients, including those who are unable to undergo an invasive tumour biopsy, or where tissue is unavailable or of insufficient size to evaluate.

"Pursuing next generation biomarker development is a critical component of our cancer immunotherapy strategy," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Biomarkers will not only improve our understanding of immune biology but will ultimately help match our therapies and combinations to the people most likely to benefit. This blood-based TMB assay is one example of how we and our partners are advancing the science toward personalisation of cancer therapy."

The bTMB biomarker study being presented at ESMO (Free ESMO Whitepaper) was conducted using 794 plasma samples from the pivotal phase II POPLAR and phase III OAK Tecentriq studies. The purpose of the analysis was to collect initial, retrospective evidence of an association between bTMB and Tecentriq activity. These early data will inform ongoing and future prospective research to better understand the role of both TMB and bTMB as it relates to treatment with cancer immunotherapy.1

Two prospective studies in patients receiving first-line treatment for NSCLC are underway, which aim to clinically evaluate and prospectively validate our novel blood-based diagnostic assay and assess the efficacy and safety Tecentriq and/or Alecensa (alectinib) for patients with NSCLC.5

The B-F1RST study is a single-arm study evaluating the safety and efficacy of Tecentriq in first-line NSCLC and will evaluate the association between bTMB and efficacy in biomarker-unselected patients through prospective collection of blood samples that will be retrospectively tested.5

BFAST is a phase II/III global, multicentre, open-label, umbrella trial designed to evaluate the safety and efficacy of Tecentriq or Alecensa in patients with unresectable, advanced or metastatic NSCLC. Treatment selection of Tecentriq or Alecensa is based on the presence of a positive bTMB score or oncogenic somatic mutations, respectively.5

Tecentriq is currently approved in the United States for certain types of lung and bladder cancers regardless of PD-L1 expression levels. Beyond cancer immunotherapy, Roche has an extensive oncology pipeline with ongoing studies in collaboration with Foundation Medicine for molecules such as the oral AKT inhibitor ipatasertib, Alecensa, and Avastin.2
Overview of Roche bTMB presentations at ESMO (Free ESMO Whitepaper) 2017

About the retrospective POPLAR and OAK analyses
The bTMB assay was used to analyse a total of 794 plasma samples from the phase II POPLAR and phase III OAK clinical trials and found that patients with NSCLC and high bTMB experienced longer progression-free survival when treated with Tecentriq.

POPLAR is a multi-centre, international, randomised, open-label, controlled phase II study, that evaluated the safety and efficacy of Tecentriq compared to docetaxel in patients with locally advanced or metastatic NSCLC who progressed during or following a platinum-containing regimen, regardless of PD-L1 expression. OAK is a global, multi-centre, randomised, open-label, controlled phase III study that evaluated the efficacy and safety of Tecentriq compared with docetaxel. In these retrospective analyses, plasma samples from OAK and POPLAR were analysed with the blood-based TMB assay to correlate bTMB with Tecentriq clinical activity.

The biomarker evaluable population (BEP) included 211 patients in POPLAR (ITT population=287) and 583 patients in OAK (excludes patients with known EGFR/ALK mutations; ITT=850), with blood samples available for targeted genomic sequencing.