On February 18, 2017 Nektar Therapeutics (Nasdaq: NKTR) reported that positive Phase 1 clinical data for Nektar’s lead immuno-oncology agent, NKTR-214, in patients with renal cell carcinoma (RCC) were presented at ASCO (Free ASCO Whitepaper) GU 2017 (Press release, Nektar Therapeutics, FEB 18, 2017, View Source [SID1234517754]). NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and Natural Killer (NK) cell abundance directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. The results were presented by Michael Hurwitz, MD, PhD, Assistant Professor of Medicine, Department of Medical Oncology at Yale Cancer Center and were entitled "A Novel Immune Agonist, NKTR-214, Increases the Number and Activity of CD8+ Tumor Infiltrating Lymphocytes in Patients with Advanced Renal Cell Carcinoma."

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"NKTR-214 resulted in dramatic increases in tumor-infiltrating lymphocytes (TILs) and also demonstrated encouraging anti-tumor activity, with 40% of RCC patients experiencing tumor reductions, including one patient with a partial response," said Dr. Mary Tagliaferri, Vice President, Clinical Development at Nektar. "We know that high TIL levels are correlated with clinical response and longer survival in patients treated with checkpoint inhibitor therapies and can be the best predictor of response. NKTR-214’s unique mechanism, favorable safety profile and clinical activity support our combination trials of NKTR-214 with existing checkpoint inhibitors, such as nivolumab and atezolizumab, but also with other I-O mechanisms in development."

Clinical benefit and safety data were presented on 15 patients from the trial with renal cell carcinoma who were treated with single-agent NKTR-214:

6/15 (40%) patients with RCC had radiographic reductions in tumor size per RECIST 1.1 on NKTR-214, including:
3 patients who had progressed on 1 prior tyrosine kinase inhibitor (TKI) and had also progressed on 1 prior checkpoint therapy
3 patients who had progressed on 1 prior tyrosine kinase inhibitor (TKI) and were checkpoint therapy naïve, including 1 patient who experienced an unconfirmed partial response (uPR)
NKTR-214 continues to demonstrate a favorable safety and tolerability profile with convenient, outpatient q3w or q2w administration in all patients evaluable for safety to-date.
Immune pheno-typing was conducted and biomarkers of immune activation were measured in patients with evaluable tumor biopsies and blood samples. Treatment with NKTR-214 produced a robust elevation in immune cell frequency and activation, including:

Increase in total lymphocytes and newly proliferating (Ki67+) CD4+ T cells, CD8+ T cells, and NK cells, with increases greater than 50-fold observed
Increase in CD8+ T cells of up to 10-fold in the tumor micro-environment in patients with evaluable tumor biopsies (pre-dose and post-dose at week 3)
Increase in expression of cell-surface PD-1 on T cell subsets of up to 2-fold in the tumor micro-environment
Nektar and Bristol-Myers Squibb are collaborating to develop NKTR-214 as a potential combination treatment regimen with Bristol-Myers Squibb’s Opdivo (nivolumab) in five tumor types and eight potential indications. The Phase 1/2 clinical program will enroll up to 260 patients and will evaluate the potential for the combination of Opdivo (nivolumab) and NKTR-214 to show improved and sustained efficacy and tolerability above the current standard of care in melanoma, kidney, triple-negative breast cancer, bladder and non-small cell lung cancer patients. The initial dose-escalation trial is underway with Opdivo (nivolumab) and NKTR-214 in the indications of first-line melanoma, second-line RCC checkpoint therapy-naïve, and second-line non-small cell lung cancer (NSCLC) checkpoint therapy-naïve.

NKTR-214 is an experimental therapy designed to stimulate cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and NK cells. In preclinical studies, treatment with NKTR-214 resulted in a rapid expansion of these cells and mobilization into the tumor micro-environment.1 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines. A Phase 1/2 clinical study is ongoing to evaluate single-agent NKTR-214 in cancer patients.

The ASCO (Free ASCO Whitepaper) GU 2017 poster can be downloaded at the following url:

View Source

On February 18, 2017 Percans Oncology reported to developing and promoting susceptibility testing technologies of anti-tumor drugs with high clinical predictivity, and assisting clinicians with the best plan for individualized tumor treatment (Press release, Cothera Bioscience, FEB 18, 2017, View Source [SID1234618856]). Recently, Fortune United Partners invested in Beijing Percans Oncology Co., Ltd. as the leading investor in series-B financing.

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Established in 2012, Beijing Percans Oncology Co., Ltd. is a service company focusing on individualized tumor treatment. Through strategic cooperation with top international and domestic cancer medical centers, Percans Oncology seeks the best chemotherapy plan for postoperative tumor patients, so as to improve the effectiveness of clinical chemotherapy and maximize the survival time of patients, and promote the development of anti-tumor drug research.

The third-generation drug susceptibility testing technology, corresponding more closely to clinical applications

The new third-generation drug susceptibility testing technology i-Chemo, based on technologies such as "micro-tumor", not only continues the accuracy of predicting clinical drug response, but also greatly shortens the testing cycle and cuts the cost. The most effective treatment plan can be accurately determined among a variety of clinical drug plans within 9 days to avoid ineffective treatments.

This pioneering work can help clinicians find the most suitable medication plan for cancer patients within the best treatment period, thus enriched the connotation of precision medicine and will have a wide range of potential applications in the future. At present, Percans Oncology is working with more tumor hospitals to carry out clinical research on i-Chemo drug susceptibility testing, and further promoting related research and application in this field.

Relying on the professional teams in medicine, scientific research, product development and marketing, as well as powerful cancer drug screening technologies and highly efficient bench-to-bedside translation ability in oncological research, Percans Oncology is devoted to serve cancer patients in China and worldwide.

On February 17, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported new findings from the OlympiAD study that show its BRACAnalysis CDx test successfully identified patients with HER2-negative metastatic breast cancer who have BRCA mutations and who had improved response with Lynparza (olaparib), AstraZeneca’s PARP inhibitor (Press release, Myriad Genetics, FEB 17, 2017, View Source [SID1234517753]).

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The high level results — announced earlier today from AstraZeneca — are the first reported clinical data from the OlympiAD study (NCT02000622), which assessed the efficacy and safety of olaparib monotherapy versus physicians’ choice of chemotherapy (i.e., capecitabine, vinorelbine or eribulin) in the treatment of metastatic breast cancer. Of the 302 patients in the study, 98 percent (297/302) tested positive for germline BRCA1/2 mutations as determined by Myriad’s FDA-approved BRACAnalysis CDx test. The results demonstrated a statistically-significant improvement of progression-free survival (PFS) among BRCA-mutated patients treated with olaparib compared to those treated with physicians’ choice.

"We believe the results of the OlympiAD trial support use of the BRACAnalysis CDx test to help inform treatment decisions in the metastatic breast cancer setting and will expand the patient population who can benefit from BRCA testing," said Johnathan Lancaster, M.D., Ph.D., chief medical officer of Myriad Genetic Laboratories. "This study underscores Myriad’s commitment to our pharmaceutical partners and to advancing the field of personalized medicine so that new effective treatment options are available to patients."

It is estimated there are approximately 60,000 patients with metastatic breast cancer, two thirds of whom are not currently eligible for BRCA testing based upon family and personal history alone or current testing criteria. If approved as a new indication this would triple the number of patients with metastatic breast cancer who would benefit from BRCA testing.

The ongoing collaboration between Myriad and AstraZeneca to develop a novel companion diagnostic test to identify candidates for treatment with olaparib began in 2007. In Dec. 2014, Myriad received FDA approval for BRACAnalysis CDx to help identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with olaparib. BRACAnalysis CDx is Myriad’s first FDA-approved companion diagnostic and was the first-ever laboratory developed test reviewed and approved by the FDA.

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants eligible for treatment with Lynparza (olaparib). This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-
test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III study called OLYMPIA. This study is still open and recruiting patients internationally.

On February 17, 2017 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), reported that it presented a poster of its immunological data from its 94-patient Phase 2 trial evaluating vesigenurtacel-L (HS-410) either alone or in combination with BCG in patients with non-muscle invasive bladder cancer (NMIBC) at the 2017 Genitourinary (GU) Cancers Symposium (Press release, Heat Biologics, FEB 17, 2017, View Source [SID1234517757]). Researchers reported that HS-410, in combination with BCG, continues to be generally well-tolerated, that HS-410 activates CD8+ T cells and that these immune responders appear to have a lower recurrence rate than non-immune responders. Taken together, these data strengthen support for the vaccine mechanism of action and clinical proof-of-concept of immune activation.

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Patients were also evaluated based on their levels of tumor infiltrating lymphocytes (TIL) at the start of treatment. In the placebo arm, patients with low TIL levels at baseline had a higher incidence of disease recurrence than patients with high TIL levels at baseline. However, in the vaccine-treated group, recurrence levels were essentially the same between the high and low TIL subgroups, at 25% and 29%, respectively. The fact that these two groups of patients saw clinical outcomes that were roughly identical may warrant further evaluation.

"These data continue to support our hypothesized vaccine mechanism of action," said Jeff Hutchins, Ph.D., Heat’s Chief Scientific Officer and Senior Vice President of Preclinical Development. "Furthermore, we believe this vaccine treatment strategy could be evaluated in more advanced bladder patient populations, where immunotherapy has been shown to be effective, but where not all patients respond to therapy, likely due to insufficient T cell activation and proliferation."

As previously reported, vaccine arms did not show a statistical improvement over the placebo arm in the primary endpoint (1-year recurrence free survival). However, in keeping with clinical trial guidance, Heat continues to monitor all patients enrolled in the study for a 2-year duration.

The poster will be uploaded to the publications section of Heat’s corporate website in line with the conference’s embargo policy.

On February 17, 2017 ArQule, Inc. (Nasdaq: ARQL) and Daiichi Sankyo reported that the METIV-HCC phase 3 study of tivantinib in hepatocellular carcinoma (HCC) did not meet its primary endpoint of improving overall survival (Press release, ArQule, FEB 17, 2017, View Source [SID1234517745]).

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METIV-HCC is a biomarker-selected, double-blind, placebo-controlled, randomized phase 3 study evaluating tivantinib (2:1) versus best supportive care in patients with MET-overexpressing, inoperable HCC intolerant to or previously-treated with systemic therapy. A total of 340 patients with MET-overexpressing HCC analyzed by a validated immunohistochemical assay were randomized in the intent-to-treat population for efficacy analysis. The primary endpoint of the study is overall survival. Secondary endpoints include progression-free survival and safety. Full results from the trial will be presented at an upcoming scientific forum.

"HCC is a disease with high unmet need, especially in the second-line setting, so these results are disappointing for the patients as well as the investigators and the companies," said Paolo Pucci, Chief Executive Officer of ArQule.

"Despite the negative outcome of this study, we remain committed to applying rigorous science to unmet needs for patients with cancer," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "We would like to take this opportunity to thank all of the investigators, and especially the patients, for their participation in this study."

The ArQule investor conference call can be accessed in the "Investors and Media" section of ArQule’s website, www.arqule.com, under "Events and Presentations." You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. and using the passcode 74015633. A replay will be available two hours after the completion of the call and can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations."

About Hepatocellular Carcinoma (HCC)
Liver cancer is the sixth most common cancer globally with 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 745,000 deaths in 2012.1 HCC accounts for about 90 percent of primary liver cancers.2 Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.2

About Tivantinib (ARQ 197)
ArQule and Daiichi Sankyo have a licensing, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.