On May 18, 2016 Novartis rreported that it will highlight the strength of its oncology research programs at the upcoming 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), being held June 3-7 in Chicago (Press release, Novartis, MAY 18, 2016, View Source [SID:1234512583]). Data will demonstrate advances across several of the company’s core disease areas of focus including leukemias and lung, melanoma and breast cancers.

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"We are particularly excited to share the results from the Tasigna Treatment-free Remission trials as these represent our unwavering commitment to further understand management approaches for Philadelphia chromosome-positive chronic myeloid leukemia," said Bruno Strigini, President of Novartis Oncology. "These and other data at ASCO (Free ASCO Whitepaper) 2016 underscore our drive to advance cancer research for the benefit of patients."

Novartis data at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting will highlight the following:

The potential for some patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), treated with Tasigna (nilotinib), to achieve a sustained deep level of molecular response and maintain a major molecular response after stopping therapy – a concept called Treatment-free Remission (TFR):

Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline nilotinib: Results from the ENESTFreedom study [Abstract #7001; Saturday, June 4, 3:12 PM CDT]
Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with second-line nilotinib (NIL): First results from the ENESTop study [Abstract #7054; Monday, June 6, 8:00 AM CDT]

Update on the efficacy and safety of Tafinlar (dabrafenib) and Mekinist (trametinib) combination therapy in patients with BRAF V600-mutated cancers, including potential indications under investigation:

Genomic analysis and 3-y efficacy and safety update of COMBI-d: A Phase III study of dabrafenib (D) + trametinib (T) vs D monotherapy in patients with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma [Abstract #9502; Monday, June 6, 1:39 PM CDT]
An open-label Phase II trial of dabrafenib (D) in combination with trametinib (T) in patients with previously treated BRAF V600E-mutant advanced non-small cell lung cancer (NSCLC; BRF113928) [Abstract #107; Monday, June 6, 9:57 AM CDT]
ROAR: A Phase II, open-label study in patients with BRAF V600E-mutated rare cancers to investigate the efficacy and safety of dabrafenib (D) and trametinib (T) combination therapy [Abstract # TPS2604; Sunday, June 5, 8:00 AM CDT]
Update on CTL019, an investigational Chimeric Antigen Receptor T cell (CAR T) therapy, in relapsed/refractory pediatric acute lymphoblastic leukemia (ALL):

Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL [Abstract #3011; Monday, June 6, 4:54 PM CDT]
Ongoing investigation of established and pipeline therapies for patients with unmet needs:

Long-term outcomes of ruxolitinib (RUX) therapy in patients with myelofibrosis (MF): 5-year update from COMFORT-I [Abstract #7012; Monday, June 6, 11:30 AM CDT]**
Phase I study of the safety and efficacy of the cMET inhibitor capmatinib (INC280) in patients (pts) with advanced cMET+ non-small cell lung cancer (NSCLC) [Abstract #9067; Saturday, June 4, 8:00 AM CDT]
Additional notable data from Novartis’ core disease areas of focus include:

Breast Cancer:

A randomized trial (MA.17R) of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer [Abstract #LBA1; Sunday, June 5, 1:40 PM CDT]
Patient-reported outcomes from MA.17R: A randomized trial of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer [Abstract #LBA506; Monday, June 6, 3:15 PM CDT]
Correlation of PIK3CA mutations in cell-free DNA (cfDNA) and efficacy of everolimus (EVE) in metastatic breast cancer: Results from BOLERO-2 [Abstract #519; Sunday, June 5, 11:30 AM CDT]
Prevention of everolimus/exemestane (EVE/EXE) stomatitis in postmenopausal (PM) women with hormone receptor-positive (HR+) metastatic breast cancer (MBC) using a dexamethasone-based mouthwash (MW): Results of the SWISH trial [Abstract #525; Sunday, June 5, 8:00 AM CDT]
Evaluation of lapatinib as a component of neoadjuvant therapy for HER2+ operable breast cancer: 5-year outcomes of NSABP protocol B-41 [Abstract #501; Monday, June 6, 1:27 PM CDT]
Ribociclib (LEE011) and letrozole in estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer (aBC): Phase Ib safety, preliminary efficacy and molecular analysis [Abstract #568; Sunday, June 5, 8:00 AM CDT]

Lung Cancer:

Genetic landscape of ALK+ non-small cell lung cancer (NSCLC) patients and response to ceritinib in ASCEND-1 [Abstract #9064; Saturday, June 4, 8:00 AM CDT]
Phase II safety and efficacy results of a single-arm Ph Ib/II study of capmatinib (INC280) + gefitinib in patients with EGFR-mutated (mut), cMET-positive (cMET+) non-small cell lung cancer (NSCLC) [Abstract #9020; Saturday, June 4, 3:00 PM CDT]
Hematology:

PILLAR-2: A randomized, double-blind, placebo-controlled, Phase III study of adjuvant everolimus (EVE) in patients (pts) with poor-risk diffuse large B-cell lymphoma (DLBCL) [Abstract #7506; Sunday, June 5, 11:45 AM CDT]
ReTHINK: A randomized, double-blind, placebo-controlled, multicenter, Phase III study of ruxolitinib in early myelofibrosis patients [Abstract #TPS7080; Monday, June 6, 8:00 AM CDT]**
Patient reported outcomes (PROs) of multiple myeloma (MM) patients treated with panobinostat (PAN) after >=2 lines of therapy based on the international Phase III, randomized, double-blind, placebo-controlled, PANORAMA-1 trial [Abstract #8054; Monday, June 6, 8:00 AM CDT]
Other Tumor Types:

A first-in-human phase I study of the anti-PD-1 antibody PDR001 in patients with advanced solid tumors [Abstract #3060; Sunday, June 5, 8:00 AM CDT]
BERIL-1: A Phase II, placebo-controlled study of buparlisib (BKM120) plus paclitaxel vs placebo plus paclitaxel in patients with platinum-pretreated recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) [Abstract #6008; Sunday, June 5, 10:12 AM CDT]
BERIL-1: Biomarker results from targeted sequencing of circulating tumor DNA (ctDNA) and archival tissue in a randomized Phase II study of buparlisib (BKM120) or placebo + paclitaxel in patients with head and neck squamous cell carcinoma (HNSCC) [Abstract #6045; Saturday, June 4, 1:00 PM CDT]
A Phase II study of the efficacy and safety of the cMET inhibitor capmatinib (INC280) in patients (pts) with advanced hepatocellular carcinoma (HCC) [Abstract #4074; Saturday, June 4, 8:00 AM CDT]
Everolimus (EVE) in advanced, nonfunctional, well-differentiated neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin: Second interim overall survival (OS) results from the RADIANT-4 study [Abstract #4090; Saturday, June 4, 8:00 AM CDT]
Genomic mutation profiling (GMP) and clinical outcome in patients (pts) treated with ribociclib (CDK4/6 inhibitor) in the Signature program [Abstract 2528; Sunday, June 5, 8:00 AM CDT]
Throughout the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting, Novartis Oncology will host dedicated content on the company website (View Source) that will feature unique insights and perspectives on emerging areas of cancer care and research.

Product Information
Approved indications for products vary by country and not all indications are available in every country. The product safety and efficacy profiles have not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that compounds will become commercially available with additional indications.

For full prescribing information, including approved indications and important safety information about marketed products, please visit
View Source .

Because INC280, CTL019, LEE011, BKM120 and PDR001 are investigational compounds, the safety and efficacy profiles have not yet been fully established. Access to these investigational compounds is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Because of the uncertainty of clinical trials, there is no guarantee that INC280, CTL019, LEE011, BKM120 and PDR001 will ever be commercially available anywhere in the world.

On May 18, 2016 Array BioPharma (NASDAQ: ARRY) reported that they will present additional data on their late-stage candidates binimetinib and encorafenib in NRAS-mutant melanoma and BRAF-mutant colorectal cancer, respectively, at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois on June 3-7 (Press release, Array BioPharma, MAY 18, 2016, View Source;p=RssLanding&cat=news&id=2169509 [SID:1234512536]).

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"We look forward to presenting data at ASCO (Free ASCO Whitepaper) from our pivotal NEMO trial of binimetinib in NRAS-mutant melanoma, which met its primary endpoint of progression free survival (PFS), and plan to submit a New Drug Application (NDA) for binimetinib next month," said Ron Squarer, Chief Executive Officer of Array BioPharma. "Importantly, in the pre-specified sub-group of patients who received prior treatment with immunotherapy, including ipilimumab and nivolumab, median PFS was 5.5 months for patients treated with binimetinib compared to 1.6 months for patients treated with dacarbazine. These results are encouraging given the limited treatment options available to patients with NRAS-mutant melanoma beyond immunotherapy."

"We are also pleased to share results from our Phase 2 trial of encorafenib and cetuximab containing-regimens in BRAF-mutant colorectal cancer patients who have progressed after one or more prior therapies," added Mr. Squarer. "Data from this study suggest that median overall survival (OS) for these patients may exceed one year which is substantial when compared to historical published benchmarks for this population, which range between four to six months. We expect to present updated OS data from this trial at ASCO (Free ASCO Whitepaper) and plan to initiate a global Phase 3 trial in BRAF-mutant colorectal cancer later this year."

BINIMETINIB

In the Phase 3 NEMO (NRAS MELANOMA AND MEK INHBITOR) trial, 402 patients with NRAS-mutant melanoma were randomized 2:1 to receive binimetinib or dacarbazine, respectively. Eighty-five of the 402 patients received prior treatment with immunotherapy.

The primary endpoint of PFS was met, with a hazard ratio of 0.62, [95% CI 0.47-0.80] and a p-value of less than 0.001. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm.
Importantly, an improvement in median PFS in binimetinib-treated patients was observed in the pre-specified sub-group of patients who received prior treatment with immunotherapy. The median PFS on the binimetinib arm was 5.5 months versus 1.6 months on the dacarbazine arm [HR=0.46 (95% CI 0.26-0.81)].
Confirmed overall response rate (ORR) and disease control rate (DCR) were 15 percent (95% CI, 11-20 percent) and 58 percent (95% CI, 52-64 percent) for all patients receiving binimetinib, respectively, versus 7 percent (95% CI, 3-13 percent) and 25 percent (95% CI, 18-33 percent) for patients receiving dacarbazine, respectively.
Grade 3/4 adverse events (AEs) reported in greater than or equal to 5 percent of patients receiving binimetinib included increased creatine phosphokinase (CPK) and hypertension.
Array expects to present additional OS data at ASCO (Free ASCO Whitepaper).
Data from the Phase 3 study will be featured during an oral presentation on Monday, June 6, 1:15 p.m. CT:

Abstract 9500: Results of NEMO: A phase III trial of binimetinib (BINI) vs dacarbazine (DTIC) in NRAS-mutant cutaneous melanoma
Presenter: Reinhard Dummer, M.D.
ENCORAFENIB

In the Phase 2 BRAF-mutant colorectal cancer trial, 102 patients were randomized 1:1 to receive encorafenib and cetuximab with or without alpelisib:

Median PFS was 5.4 months and 4.2 months for the triplet and doublet regimens, respectively.
An early analysis of median OS exceeded one year for the triplet regimen and was not reached for the doublet regimen. Updated interim median OS analysis for both regimens will be presented at ASCO (Free ASCO Whitepaper).
Confirmed ORR was 27 percent (95% CI, 16-41 percent) for the triplet regimen and 22 percent (95% CI, 12-36 percent) for the doublet regimen.
Grade 3/4 AEs occurring in greater than 10 percent of patients in either arm included anemia, hyperglycemia and increased lipase.
Historical published PFS and OS results after first-line treatment range between 1.8 to 2.5 months and four to six months, respectively, and published response rates from various studies in this population range between 6 percent to 8 percent.

Data from the Phase 2 study will be presented on Saturday, June 4, 8:00 – 11:30 a.m. CT:

Abstract 3544: Phase 2 results: encorafenib (ENCO) and cetuximab (CETUX) with or without alpelisib (ALP) in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC)
Presenter: Josep Tabernero, M.D., Ph.D.
Additional data from Array BioPharma and partner compounds will also be presented at ASCO (Free ASCO Whitepaper) across a variety of tumor types.

All abstracts can be accessed through the ASCO (Free ASCO Whitepaper) website, View Source After the presentations and posters are public, they will be available as PDFs on Array’s website at www.arraybiopharma.com.

About NRAS-Mutant Melanoma
Activating NRAS mutations are present in up to 20 percent of patients with metastatic melanoma, and is a poor prognostic indicator for these patients. Treatment options for this population remain limited beyond immunotherapy, and patients face poor clinical outcomes and high mortality.

About BRAF-Mutant Colorectal Cancer
Colorectal cancer is the third most common cancer among men and women in the United States, with more than 134,000 new cases and nearly 50,000 deaths from the disease projected in 2016.

About Binimetinib and Encorafenib
MEK and BRAF are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as melanoma, non-small cell lung, colorectal and thyroid cancers. Binimetinib is a late-stage small molecule MEK inhibitor and encorafenib is a late-stage small molecule BRAF inhibitor, both of which target key enzymes in this pathway.

Binimetinib and encorafenib are being studied in Phase 3 trials in advanced cancer patients, including: NRAS-mutant melanoma (NEMO, binimetinib single agent) and BRAF-mutant melanoma in combination with encorafenib (COLUMBUS, binimetinib and encorafenib). Activating BRAF mutations are present in approximately 50 percent of patients with metastatic melanoma. NRAS-mutant melanoma represents the first potential indication for binimetinib, with a projected regulatory filing estimated in the first half of 2016. Array also projects COLUMBUS top-line results availability during the third quarter of 2016. In addition, Array plans to initiate a Phase 3 global registration trial in patient with BRAF-mutant colorectal cancer later this year.

On May 18, 2016 Trillium Therapeutics Inc. (NASDAQ: TRIL; TSX: TR), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported it will present its TTI-621 (SIRPaFc) immune checkpoint inhibitor program at the Trials in Progress Session of the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held in Chicago from June 3-7 (Filing, 6-K, Trillium Therapeutics, MAY 18, 2016, View Source [SID:1234512630]).

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Details of Trillium’s ASCO (Free ASCO Whitepaper) presentation are as follows:

Presentation Type: Poster
Abstract #: TPS7585
Title: A phase 1 study of TTI-621, a novel immune checkpoint inhibitor targeting CD47, in subjects with relapsed or refractory hematologic malignancies
Presenter: Stephen Maxted Ansell, M.D., Ph.D., Division of Hematology, Mayo Clinic
Track: Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia
Time/Location: Monday, June 6, 8-11:30 a.m. in Hall A, Poster Board #134b

On May 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 updated data from the ongoing clinical trials of FPA144 and FP-1039 will be presented during the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 3-6, 2016, in Chicago (Press release, Five Prime Therapeutics, MAY 18, 2016, View Source [SID:1234512537]). The presentation abstracts are now available online at the meeting website: View Source Information contained in the abstracts was as of the time of submission in February 2016. Five Prime intends to announce more detailed results at the time of the presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting.

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Further data on safety and activity from the Phase 1 trial evaluating FPA144, an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced, FGFR2b isoform-selective monoclonal antibody, as a single agent in patients with FGFR2b+ gastric cancer and advanced solid tumors will be featured in an oral presentation:

ABSTRACT 2502
Antitumor activity and safety of FPA144, an ADCC-enhanced, FGFR2b isoform-selective monoclonal antibody, in patients with FGFR2b+ gastric cancer and advanced solid tumors
Oral Abstract Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Date/Time: Monday, June 6, 2016, 8:24 AM – 8:36 AM Central Time
Location: E354b

Preliminary dose escalation data from the FPA144 trial were presented during the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2016.

Additionally, data on the safety, response rate and duration of response of FP-1039, an FGF ligand trap, combined with standard of care chemotherapy to treat malignant pleural mesothelioma patients in GlaxoSmithKline’s Phase 1b trial will be highlighted in a poster presentation:

ABSTRACT 8557/POSTER BOARD #185
Multi-arm, open-label Phase 1b study of FP-1039/GSK3052230 with chemotherapy in malignant pleural mesothelioma (MPM)
Poster Session: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Date/Time: Saturday, June 4, 2016, 8:00 AM – 11:30 AM Central Time
Location: Hall A

Initial data from the Phase 1b trial of FP-1039 were released during the World Conference on Lung Cancer in September 2015, but the majority of mesothelioma patients enrolled at the time were not yet evaluable.

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. 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.

FPA144 is designed to block tumor growth through two distinct mechanisms. First, 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 and T cells. Second, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. When combined with PD-1 blockade, FPA144 has shown an additive effect in tumor growth inhibition in preclinical models. Five Prime retains global development and commercialization rights to FPA144.

About FP-1039

FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells where they would otherwise stimulate cancer cell division and/or angiogenesis. However, FP-1039 does not bind to certain "hormonal" FGFs, including FGF-23, which regulates phosphate levels in the blood. As a result, treatment with FP-1039 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23.

GlaxoSmithKline is completing the ongoing Phase 1b trial in malignant pleural mesothelioma and will transfer its development and commercialization rights for FP-1039 back to Five Prime during 2016. Five Prime will base decisions on further development of FP-1039 in mesothelioma on the quality and duration of responses from the trial, as well as considerations such as drug supply and manufacturing.

On May 18, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) REPORTED that interim results from the Company’s ongoing Phase 1, multi-center dose-escalation study of the gene therapy candidate Ad-RTS-hIL-12 + orally-administered veledimex in patients with recurrent or progressive glioblastoma will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 3-7, 2016, at McCormick Place in Chicago, Illinois (Press release, Ziopharm, MAY 18, 2016, View Source [SID:1234512565]). Ad-RTS-hIL-12 + veledimex is a novel viral gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a pro-inflammatory cytokine critical for stimulating anti-cancer immune responses.

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Glioblastoma is an aggressive primary brain tumor affecting approximately 74,000 people worldwide each year.i, ii Recurrent glioblastoma is an aggressive cancer with one of the lowest 3-year survival rates, at 3%, among all cancers.iii For patients who have experienced multiple recurrences the prognosis is particularly poor, with a median overall survival (OS) of 6-7 months, while OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iv, v

The primary objective of the study is to determine the safety and tolerability of a single intratumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the Ad-RTS-hIL-12 + veledimex maximum tolerated dose, the immune responses elicited by Ad-RTS-hIL-12 + veledimex, and assessment of biologic response. Eleven patients with recurrent high-grade gliomas (one with grade III and ten with grade IV) have been treated to date with Ad-RTS-hIL-12 through direct injection into their brain tumors, including seven patients in the first dose cohort (veledimex dosed at 20 mg) and four in the ongoing second dose cohort (veledimex dosed at 40 mg). Veledimex was taken orally to activate the production of IL-12 from the tumor site and stimulate an immune response.

Patients enrolled in this multi-center study have all failed standard therapy, with nine of eleven patients failing additional salvage treatments, for a mean of 2.7 prior lines of therapy in cohort one and 2.0 prior lines in cohort two. No enrollment restrictions were placed on tumor size or location within the supratentorial space. Overall median follow-up for patients enrolled in the trial is 6.2 months with 10 of 11 alive. In the fully-enrolled cohort one, 6 of 7 (86%) patients remain alive with a median follow up of 6.8 months. Enrollment in cohort two is ongoing. Even at its lowest dose, the presence of IL-12 in the bloodstream could be detected, demonstrating that veledimex is bioavailable and crosses the blood brain barrier at sufficient levels to turn on the RheoSwitch (RTS) and generate IL-12, which could be measured in the blood stream. Furthermore, for those patients that experienced adverse events associated with the treatment, discontinuing veledimex reversed these adverse events.

"Early results observed in the limited number of patients who have been treated with Ad-RTS-hIL-12 + veledimex are very encouraging for a Phase 1 study," said Ennio Antonio Chiocca, M.D., Ph.D., Harvey W. Cushing Professor of Neurosurgery, Department of Surgery, Harvard Medical School, Surgical Director, Center for Neuro-oncology, Dana-Farber Cancer Institute, Chairman, Neurosurgery, Brigham And Women’s Hospital and Co-Director, Institute for the Neurosciences, Brigham And Women’s Hospital. "Virus-based gene therapy used to stimulate an immunological response in the brain is at the frontier of innovation in treatment, with Ad-RTS-hIL-12 offering perhaps the most controllable approach within this field. In this study, we see encouraging signs of immune activation following the administration of Ad-RTS-hIL-12 + veledimex."

Overall Ad-RTS-hIL-12 + veledimex was well tolerated. All serious adverse events and Grade 3 related toxicities were rapidly reversible upon discontinuation of veledimex. The most common related adverse events included headache, nausea/vomiting, fever, white blood cell/leukocyte count decrease, platelet count decrease and liver function test increase. Four subjects had related serious adverse events.

"Because the brain is a segregated and fragile environment, the ability to turn an immune response on and off is critical to balancing efficacy and tolerability," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "As we continue to follow patients with extremely guarded prognoses in this multi-center trial, we hope that these promising early trends in survival are maintained. Our goal, once we reach an optimal dose, will be to promptly initiate registration trial discussions with regulators."

Dr. Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM, added: "Basing our approach on the genetic engineering of adenovirus offers a simpler strategy than replicating viral-therapy options, one that can be rapidly controlled via a drug activating a gene switch, and one that does not rely on intratumoral catheterization. We look forward to testing Ad-RTS-hIL-12 + veledimex not just on its own, but in combination with other immuno-oncology approaches, including checkpoint inhibitors and natural killer cells, in clinical trials that we plan to start this year and next. Our data suggest that patients can take a drug by mouth to activate the immune response in their tumors with exciting results."

Ad-RTS-hIL-12 + veledimex has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with malignant glioma.

ASCO Presentation Details

Title: Effect of controlled intratumoral viral delivery of Ad-RTS-hIL-12 + oral veledimex in subjects with recurrent or progressive glioma
Poster Session: Central Nervous System Tumors
Date and Time: Saturday, June 4, 2016 1:00 PM — 4:30 PM CT
Abstract Number: 2052
Poster: #239
Location: Hall A

In addition to the GBM study, a study design for the Company’s Phase 1b/2 clinical trial of Ad-RTS-hIL-12 + veledimex in locally advanced or metastatic breast cancer will be outlined at the ASCO (Free ASCO Whitepaper) annual meeting. The study, which is being conducted at the Memorial Sloan Kettering Cancer Center in New York, is designed to examine the safety, tolerability and efficacy of Ad-RTS-hIL-12 immunotherapy given following standard of care chemotherapy in up to 40 women with locally advanced or metastatic breast cancer of all subtypes. The Company expects that outcome data from this study will be presented at a scientific meeting in the second half of the year.

Title: Phase 1b/2 study of intratumoral Ad-RTS-hIL-12 + veledimex in patients with chemotherapy-responsive locally advanced or metastatic breast cancer
Poster Session: Developmental Therapeutics—Immunotherapy
Date and Time: Sunday, June 5, 2016 8:00 AM — 11:30 AM CT
Abstract Number: TPS3097
Poster: #418a
Location: Hall A