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Preclinical Data Presented at AACR Demonstrate that Combining NKTR-214 with Checkpoint Blockade is Superior to Dual Checkpoint Inhibition in Increasing Clonality of the T Cell Receptor (TCR) Repertoire and T Cell Tumor Infiltration

On April 18, 2016 Nektar Therapeutics (NASDAQ: NKTR) reported new preclinical data for the company’s investigational immuno-stimulatory cytokine therapy, NKTR-214, which demonstrate both its activity as a single-agent and its synergistic activity with checkpoint blockade (Press release, Nektar Therapeutics, APR 18, 2016, View Source [SID:1234510977]). In a TCR repertoire analysis conducted to assess both anti-tumor T cell clonality and T cell tumor infiltration (TIL clonality and infiltration), the combination of NKTR-214 and a checkpoint inhibitor resulted in dramatically higher increases for both parameters as compared to dual checkpoint inhibition. These data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA on April 17, 2016.

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TIL clonality establishes the frequency of T cells with a specific TCR Vβ and TCR Jβ chain usage at the tumor site, which suggests increased CD8-positive effector T cell function against the specific tumor.1 The concomitant presence of both TIL clonality and infiltration has been significantly correlated with clinical response and better survival outcomes in patients.1 In a CT26 colon carcinoma model, sequencing for TCRs in the tumor was conducted using Adaptive Biotechnologies’ ImmunoSEQ platform. Measurements of TIL clonality and infiltration were assessed seven days after treatment. NKTR-214 as a single-agent led to superior increases in TIL clonality and infiltration as compared to either anti-CTLA-4 or anti-PD-1 therapy alone. The combination of NKTR-214 with either mode of checkpoint inhibition led to superior increases in both TIL clonality and infiltration relative to the combination of CTLA-4 and PD-1 inhibitors. The highest increases occurred when NKTR-214 was added to an anti-PD-1 therapy.

"We are particularly excited by these new preclinical data for the combination of NKTR-214 with a checkpoint inhibitor which show an induced oligoclonal T cell response along with high TIL infiltration, "said Dr. Jonathan Zalevsky, Vice President of Biology at Nektar Therapeutics. "These data demonstrate that the addition of NKTR-214 to either an anti-CTLA-4 or anti-PD-1 agent could improve T cell clonality differences over checkpoint blockade therapies."

NKTR-214 is an investigational CD122-biased agonist currently in Phase 1/2 clinical development. NKTR-214 is designed to stimulate the patient’s own immune system to kill tumor cells by preferentially activating production of specific immune cells which promote tumor killing, including CD8-positive T cells and Natural Killer (NK) cells, within the tumor micro-environment. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these types of T cells.2

In studies conducted in multiple established tumor models presented at AACR (Free AACR Whitepaper), NKTR-214 demonstrated activity as both a single-agent and when co-dosed with either an anti-PD-1 agent or an anti-CTLA-4 agent. In a tumor re-challenge study conducted in an EMT6 colon carcinoma model, sequential dosing of anti-CTLA-4 followed by NKTR-214 resulted in durable immunity, with complete responders resisting a tumor re-challenge. Following a second re-challenge, 100% of the animals remained tumor-free without additional treatment.

"Our latest preclinical findings continue to show that treatment with NKTR-214 either as a single-agent or in combination with checkpoint blockade is superior to single or dual checkpoint inhibition in multiple models," added Steve Doberstein, PhD, Senior Vice President and Chief Scientific Officer of Nektar Therapeutics. "These new data emphasize the cellular mechanisms underlying the remarkable efficacy of NKTR-214 in our preclinical models of cancer."

The data presentation at AACR (Free AACR Whitepaper) entitled, "Durable antitumor activity of the CD122-biased immuno-stimulatory cytokine NKTR-214 combined with immune checkpoint blockade," can be accessed at View Source

In preclinical studies, NKTR-214 demonstrated a highly favorable mean ratio of 450:1 within the tumor micro-environment of CD8-positive effector T cells relative to regulatory T cells.3 Furthermore, the pro-drug design of NKTR-214 enables an antibody-like dosing regimen for an immuno-stimulatory cytokine.4

About the NKTR-214 Phase 1/2 Clinical Study

A Phase 1/2 clinical study is underway to evaluate NKTR-214 in patients with advanced solid tumors, including melanoma, renal cell carcinoma and non-small cell lung cancer. The first stage of this study, which is expected to be complete in the second half of 2016, is evaluating escalating doses of single-agent NKTR-214 treatment in approximately 20 patients with solid tumors. The primary objective of the first stage of the study is to evaluate the safety and efficacy of NKTR-214 and to identify a recommended Phase 2 dose. In addition, the study will also assess the immunologic effect of NKTR-214 on tumor-infiltrating lymphocytes (TILs) and other immune cells in both blood and tumor tissue, and it will also include TCR repertoire profiling. Dose expansion cohorts are planned to evaluate NKTR-214 in specific tumor types, including melanoma, renal cell carcinoma and non-small cell lung cancer.

The NKTR-214 clinical study is being conducted initially at two primary investigator sites: MD Anderson Cancer Center under Drs. Patrick Hwu and Adi Diab; and Yale Cancer Center, under Drs. Mario Sznol and Michael Hurwitz. Patients and physicians interested in the ongoing NKTR-214 Study can visit the "Clinical Trials" section of www.mdanderson.org using identifier 2015-0573 or visit View Source

IPI-549 Alters the Immune-Suppressive Microenvironment and Enhances the Activity of Checkpoint Inhibitors in Preclinical Models

On April 18, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported new preclinical data for IPI-549, an orally administered immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma) (Press release, Infinity Pharmaceuticals, APR 18, 2016, View Source;p=RssLanding&cat=news&id=2157820 [SID:1234510975]). Preclinical data in multiple solid tumor models demonstrate that IPI-549 targets immune cells and alters the immune-suppressive microenvironment, promoting an anti-tumor immune response that leads to tumor growth inhibition. Data also demonstrate that IPI-549 enhances the effects of checkpoint inhibitors, resulting in improved survival in murine models. These data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans, Louisiana. A Phase 1 clinical study is under way to explore the safety and activity of IPI-549 both as a monotherapy and in combination with anti-PD-1 antibody therapy, a type of checkpoint inhibitor.

"While advances in our understanding of the immune response to cancer have resulted in new therapies for patients, additional treatments are needed that can offer even more patients the chance for prolonged survival," stated Jedd Wolchok, M.D., Ph.D., chief of Melanoma and Immunotherapeutics Service, Lloyd J. Old/Ludwig Chair in Clinical Investigation Department of Medicine and Ludwig Center, at Memorial Sloan Kettering Cancer Center and lead investigator for the Phase 1 clinical study of IPI-549. "Emerging data from our collaboration with Infinity’s discovery team provide additional rationale for combining IPI-549 with checkpoint inhibitors, and I am pleased to be leading the Phase 1 study for this program."

Preclinical Data for IPI-549 Presented at the AACR (Free AACR Whitepaper) Annual Meeting 2016 (Abstract #554)
Infinity researchers, in collaboration with researchers at Memorial Sloan Kettering Cancer Center, presented preclinical data for IPI-549 in a poster entitled, "Checkpoint blockade therapy is improved by altering the immune suppressive microenvironment with IPI-549, a potent and selective inhibitor of PI3K-gamma, in preclinical models."

In preclinical models, treatment with IPI-549 leads to a decrease in tumor-associated immune suppressive myeloid cells. IPI-549 treatment also leads to a decrease in FOXP3 T-regulatory cells, which have immune-suppressive effects, and an increase in intratumoral CD8+ T-cells, which are known to play a role in inhibiting tumor growth. Taken together, these data suggest that through its effect on myeloid cells and T-cells, IPI-549 has the potential to disrupt the immune-suppressive microenvironment and enable a heightened anti-tumor immune response.

Preclinical data in murine models show that treatment with IPI-549 in combination with anti-CTLA4 or anti-PD-L1, two types of checkpoint inhibitors, results in greater tumor growth inhibition compared to monotherapy treatment. Additionally, IPI-549 in combination with anti-PD-1 increased the number of complete responses and improves survival. Re-implantation of tumor cell lines into mice that had achieved complete responses revealed low or no tumor engraftment, suggesting sustained tumor-specific immune protection.

These data provide additional preclinical rationale for the ongoing Phase 1 clinical study designed to explore the safety and activity of IPI-549 as a monotherapy and in combination with anti–PD-1 antibody therapy in patients with selected solid tumors, including non-small cell lung cancer and melanoma (ClinicalTrials.gov identifier NCT02637531).

Infinity is also developing duvelisib, an investigational, oral, dual inhibitor of PI3K-delta and PI3K-gamma. The PI3K pathway is also known to play a critical role in regulating the growth and survival of certain types of blood cancers. Duvelisib is being evaluated in registration-focused studies, including DYNAMOTM, a Phase 2 study in patients with refractory indolent non-Hodgkin lymphoma (iNHL), BRAVURA, a Phase 3 study in patients with relapsed iNHL, and DUOTM, a Phase 3 study in patients with relapsed/refractory chronic lymphocytic leukemia. For additional information about clinical studies of duvelisib, please visit www.infi.com or www.clinicaltrials.gov.

About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

Duvelisib and IPI-549 are investigational compounds and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

Five Prime Therapeutics Announces New Pre-Clinical Data on FPA144 Presented at the 2016 AACR Annual Meeting

On April 18, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that new preclinical data on FPA144 were featured today in a poster presentation from 8 AM to 12 PM (CDT) during the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 16-20, in New Orleans (Press release, Five Prime Therapeutics, APR 18, 2016, View Source [SID:1234510972]).

The poster titled "FPA144, a Therapeutic Monoclonal Antibody Targeting the FGFR2b Receptor, Promotes Antibody Dependent Cell-Mediated Cytotoxicity and Stimulates Sensitivity to PD-1 in the 4T1 Breast Tumor Model in Mice" will be made available on the publications page of the Five Prime website.

"The ability of FPA144 to both recruit and drive an innate response with NK cells followed by an adaptive response with T cells is new and striking biology," said Drew Pardoll, M.D., Ph.D., Seraph Professor of Oncology, Medicine, Pathology and Molecular Biology and Genetics at the Johns Hopkins University of Medicine. "Driving this immune cascade in a patient’s tumor could provide a new therapeutic mechanism for treating solid tumors."

FPA144 is an FGFR2b-specific humanized monoclonal antibody designed to treat patients with cancers that overexpress FGFR2b. FPA144 is a targeted immunotherapy that Five Prime engineered to recruit NK cells into the tumor microenvironment and kill cancer cells by antibody-dependent cell-mediated cytotoxicity (ADCC).

"We are excited by the results we’ve seen in this model. Surprisingly, they suggest that FPA144 can drive an anti-tumor response that involves multiple immune cell types. The upregulation of PD-L1 suggests that combination with an anti-PD-1 agent could yield even more activity," said Robert Sikorski, M.D., Ph.D., Senior Vice President of Global Clinical Development at Five Prime. "Based on these results and the preliminary clinical data we reported in January, we are considering opportunities to evaluate FPA144 in immuno-oncology combination therapies and in tumors types beyond gastric cancer, including those with moderate levels of FGFR2b expression."

Five Prime evaluated the immune cell recruitment and anti-tumor effects of FPA144 in the orthotopic 4T1 model of breast cancer. In this model, the FGFR2 gene is not amplified and tumor cells express only moderate levels of FGFR2b. Doses of FPA144 or FPA144 N297Q (a modified antibody lacking Fc effector function) were administered at Day 0 and Day 3 and tumor histology and FACS were conducted at Day 1 and Day 4. The following was observed with FPA144 treatment:

24 Hours Post 1st Dose 24 Hours Post 2nd Dose
NK cell infiltration within the tumor Persistence of NK cells
Increase in PD-L1-positive cells within the tumor Persistence of PD-L1-positive cells
No change in T cells Increase in T cells within the tumor

Furthermore, therapeutic treatment with FPA144 in this model resulted in a reduction in tumor burden (33%, P < 0.001), while FPA144 N297Q neither inhibited tumor growth nor led to the recruitment of NK cells. These data provide further evidence of the ability of FPA144 to increase NK and T cell numbers within a tumor and suggest that its enhanced ADCC activity may play an important mechanistic role in anti-tumor efficacy in cancers with modest FGFR2b expression.

Additionally, the 4T1 model was used to evaluate the anti-tumor effect of FPA144 alone and in combination with an anti-PD-1 antibody (RMP1-14). Following biweekly dosing, tumor volume was assessed at day 19. Although anti-PD-1 treatment alone did not inhibit tumor growth, treatment with anti-PD-1 in combination with FPA144 inhibited tumor growth by 49% (P < 0.001). Collectively, these results suggest that FPA144 alters the immune cell composition of the tumor microenvironment in a way that primes the tumor to respond to anti-PD-1 therapy, and an additive anti-tumor effect is observed when FPA144 is combined with PD-1 blockade.

Dose expansion is ongoing in the Phase 1 monotherapy trial of FPA144 in patients with gastric cancer, a disease in which FGFR2b protein overexpression and FGFR2 gene amplification have been associated with poor prognosis. Preliminary data showing anti-cancer activity during the dose escalation portion of the trial were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2016. Updated data from the trial have been accepted for oral presentation during the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2016.

About FPA144

FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FPA144 is designed to block tumor growth through two distinct mechanisms. First, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. Second, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

Epizyme Presents Data from Tazemetostat Clinical Pharmacology Studies at American Association for Cancer Research Annual Meeting 2016

On April 18, 2016 Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients, reported data from clinical studies that investigated the effect of food intake on the pharmacokinetics of tazemetostat, the company’s lead investigational medicine, and the effect of tazemetostat on drugs that are metabolized by the enzyme CYP3A4/5 (Press release, Epizyme, APR 18, 2016, View Source [SID:1234510971]). Epizyme reports that tazemetostat can be dosed with or without food and that the product candidate is a weak inducer of CYP3A-mediated metabolism, suggesting any potential interactions with other treatments metabolized through this pathway will be mild. The data were presented at the 2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

Tazemetostat is a first-in-class oral EZH2 inhibitor in phase 2 development for patients with non-Hodgkin lymphoma (NHL) and patients with certain genetically defined solid tumors.

"The favorable findings from these studies further support the development of tazemetostat both as a monotherapy and in combination with other agents," said Peter Ho, M.D., Ph.D., Chief Medical Officer, Epizyme. "People living with cancer are often treated with a number of concomitant therapies, so the reduced potential for drug-drug interactions is an important consideration in treatment decision making. Additionally, the ability to take tazemetostat with or without food greatly enhances dosing convenience for patients we are treating."

Epizyme presented results from a 13-patient study on the effect of food on the pharmacokinetics of tazemetostat in subjects with advanced solid tumors or B-cell lymphomas (abstract CT031, poster #12). Pharmacokinetic studies serve to provide information about the absorption and metabolism of medicinal compounds. The area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) are pharmacokinetic parameters of the overall exposure to a drug following administration. Study findings showed that:

AUC decreased by 7 percent and Cmax decreased by 28 percent when patients consumed a high-fat meal prior to drug administration.
There was no observed clinically relevant effect of food intake on tazemetostat’s overall exposure.
Epizyme also presented results of a single-sequence, open-label crossover study of tazemetostat administered in conjunction with midazolam, a well-understood sedative that is a preferred probe drug in pharmacokinetic studies to predict drug-drug interactions with CYP3A (abstract CT029, poster #10). In summary, data show:

Tazemetostat resulted in net induction of CYP3A-mediated midazolam metabolism
Midazolam AUC and Cmax decreased approximately 40 percent and 22 percent, respectively
Tazemetostat is shown to be a weak inducer of CYP3A-mediated metabolism
About EZH2 in Cancer

EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include non-Hodgkin lymphoma, INI1-negative cancers such as malignant rhabdoid tumors and epithelioid sarcomas, certain SMARCA4-negative solid tumors, synovial sarcoma, and a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of patients with non-Hodgkin lymphoma and for patients with certain genetically defined solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In some human cancers, aberrant EZH2 enzyme activity results in dysregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non- Proprietary Name (INN) for compound EPZ-6438.

Additional information about tazemetostat, including clinical trial information, can be found here.

DelMar’s VAL-083 Demonstrates Promise in the Treatment of Non-Small Cell Lung Cancer and Ovarian Cancer

On April 18, 2016 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that the Company’s collaborators from the University of Texas MD Anderson Cancer Center (MD Anderson) presented new pre-clinical data supporting the promising potential of its lead anti-cancer product candidate, VAL-083 (dianhydrogalactitol), in the treatment of non-small cell lung cancer (NSCLC) and ovarian cancer (Press release, DelMar Pharmaceuticals, APR 18, 2016, View Source [SID:1234510970]).

Abstract (#2157): "Enhanced in vitro activity of dianhydrogalactitol (VAL-083) in combination with platinum drugs: Impact of p53 and platinum-resistance," was presented at AACR (Free AACR Whitepaper) during the "New Drugs, Therapeutic Targets, and Treatment Approaches" session.

In summary, MD Anderson researchers presented new in vitro data from their studies with VAL-083 indicating that:

VAL-083 induces apoptosis independent of p53 status, and appears to have a distinct mode of action from platinum-based chemotherapies widely used in the treatment of NSCLC and ovarian cancer;

VAL-083 demonstrated ability to circumvent cisplatin-resistance in all ovarian cell lines tested;

VAL-083 was active against NSCLC tumors harboring T790M, p53 and/or KRAS mutations, known to confer resistance to currently available therapies; and

VAL-083 demonstrated super-additivity or synergy in combination with platinum-based chemotherapy.

"These results support VAL-083 as a viable treatment option for refractory NSCLC and ovarian cancer patients failing platinum-based therapy as well as the potential benefit of a VAL-083-platinum combination," said Jeffrey Bacha, DelMar’s chairman & CEO.

Dr. Dennis Brown, DelMar’s Chief Scientific Officer, added, "The activity of VAL-083 observed in tumors harboring mutations known to be correlated with resistant phenotypes and poor treatment outcomes provides clarity and direction as we advance toward planned clinical trials in NSCLC. We can use these biomarkers for patient selection in a personalized-medicine approach to establish clinical proof-of-concept in specific tumor sub-types representing significant unmet needs within the cancer treatment market."

DelMar previously announced plans to initiate clinical trials with VAL-083 in the treatment of NSCLC in cooperation with Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd., who is to provide funding for the trial in accordance with the terms of a collaboration agreement.

About VAL-083

VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer, and has received orphan drug designation in Europe and the U.S. for the treatment of malignant gliomas. DelMar recently announced that the FDA’s Office of Orphan Products had also granted an orphan designation to VAL-083 for the treatment of medulloblastoma.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar (temozolomide).

DelMar has been conducting a Phase I/II clinical trial in GBM patients whose tumors have progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.

Data from the Phase I dose-escalation of the study suggest that VAL-083 is well tolerated using a regimen of 40mg/m2 daily x 3 every 21 days. Dose limiting toxicity (DLT) defined by thrombocytopenia (low platelet counts) was observed at doses above 40 mg/m2. Generally, DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment.

Sub-group analysis of Phase I data suggests a dose-dependent and clinically meaningful survival benefit following treatment with VAL-083. Patients in a low dose (≤5mg/m2) sub-group had a median survival of approximately five (5) months versus median survival of approximately nine (9) months for patients in the therapeutic dose (30mg/m2 & 40mg/m2) sub-group following initiation of VAL-083 treatment. DelMar also reported increased survival at 6, 9 and 12 months following initiation of treatment with VAL-083 in the therapeutic dose sub-group compared to the low dose sub-group.

Based on these data, DelMar initiated a Phase II expansion cohort utilizing the 40mg/m2 dosing regimen in June 2015 at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO). DelMar announced the completion of enrollment in a Phase II expansion cohort in September, 2015.

Updated interim data from this ongoing study will be presented on Tuesday April 19, 2016 at the AACR (Free AACR Whitepaper) Annual Meeting in the Phase II/III Clinical Trials in Progress" session (Abstract #CT074).

Further details can be found at View Source

About NSCLC

Lung cancer is a leading cause of cancer-related mortality around the world and effective treatment for lung cancer remains a significant global unmet need despite advances in therapy. In general, prognosis for lung cancer patients remains poor, with 5-year relative survival less than 14% among males and less than 18% among females in most countries. Globally, the market for lung cancer treatment may exceed $7 billion by 2019 according to a report published by Transparency Market research.

Non-small cell lung cancer ("NSCLC") is the most common type of lung cancer. There are three common forms of NSCLC: adenocarcinomas are often found in an outer area of the lung; squamous cell carcinomas are usually found in the center of the lung next to an air tube (bronchus); and large cell carcinomas, which can occur in any part of the lung and tend to grow and spread faster than adenocarcinoma. NSCLC accounts for 85% of all lung cancer cases in the United States and approximately 90% of lung cancer cases diagnosed in China.

The current standard of care for newly diagnosed NSCLC is platinum-based combination therapy or tyrosine kinase inhibitor (TKI) therapy for patients whose cancer exhibits over expression of epidermal growth factor receptor ("EGFR") mutations. Patients exhibiting an over expression of EGFR mutations have shown an initial response rate to TKIs which exceeds the response rate for conventional chemotherapy. However, resistance to TKI therapy has emerged as an important unmet medical need commonly linked to the emergence of specific mutations such as T790M.

About Ovarian Cancer

The American Cancer Society estimates for 2015 about 21,290 women will receive a new diagnosis of ovarian cancer and approximately 14,180 women will die from ovarian cancer in the United States. Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. A woman’s risk of getting ovarian cancer during her lifetime is about 1 in 75. Her lifetime chance of dying from ovarian cancer is about 1 in 100. Although initially responsive to standard-of-care chemotherapy based on platinum-taxane combinations, most tumors recur and median survival for recurrent ovarian cancer is 12 to 24 months. According to The Cancer Genome Atlas, there is a major clinical need for treatment with alternatives that can circumvent resistance to currently available chemotherapies.