On July 6, 2015 Oncolytics Biotech reported that Dr. Devalingam Mahalingam of the Cancer Therapy and Research Centre, University of Texas Health Science Centre San Antonio, made a poster presentation at the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer (Press release, Oncolytics Biotech, JUL 6, 2015, View Source [SID:1234506168]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster, titled "Oncolytic Virus Therapy in Pancreatic Cancer: Clinical Efficacy and Pharmacodynamic Analysis of REOLYSIN in Combination with Gemcitabine in Patients with Advanced Pancreatic Adenocarcinoma," covers final results from the Company’s REO 017 Phase 2 study.

"These data suggest that this drug combination can increase median overall survival, as well as generate an approximate two-fold increase in one-year survival rates, and a five-fold increase in two-year survival rates when compared to gemcitabine therapy alone as seen in historical data," said Dr. Matt Coffey, COO of Oncolytics. "The observation of clear overall survival (OS) benefit combined with apparent limited impact on progression free survival (PFS) is increasingly becoming characteristic of immune-based therapeutic treatments. We are incorporating this finding into both our new and existing studies to ensure we follow OS where possible."

Highlights of the data presented include:

A survival analysis for 33 patients showing a median progression free survival (PFS) of four months and median overall survival (OS) of 10.2 months;
Data showing one- and two-year survival rates of 45% and 24%, respectively; and
An analysis demonstrating upregulation of immune checkpoint marker PD-L1 in post treatment tumours suggesting the potential to combine oncolytic viral therapy with anti-PD-L1 inhibitors in future trials.

Of the 29 patients evaluable for clinical response, one patient had a partial response (PR), 23 had stable disease (SD) and five had progressive disease as their best response. This translated into a clinical benefit rate (CBR) (complete response (CR) + PR + SD) of 83%.

"This is the second cancer where we have confirmed that PD-L1 is upregulated in target tumors following our collaborators initial observations of PD-L1 upregulation in glioblastoma," said Dr. Brad Thompson, President and CEO of Oncolytics. "We are currently analyzing archived samples from other completed studies and current samples from ongoing studies to determine if this is a common effect to most cancers. A systemic viral therapy that generally led to upregulation of PD-L1 would allow increased use of anti PD-L1 drugs in cancers where there is insufficient PD-L1 to make therapy possible."

REO 017 is a U.S. Phase 2, single-arm clinical trial using intravenous administration of REOLYSIN in combination with gemcitabine (Gemzar) in chemotherapy-naïve patients with advanced or metastatic pancreatic cancer. Eligible patients were treated with gemcitabine at 800 mg/m2 on days 1 and 8, and REOLYSIN at 1×1010 TCID50 administered IV on days 1, 2, 8 and 9 every 3 weeks. Tumor assessment was performed every two cycles. The trial enrolled 33 evaluable patients (34 total) using a one sample, two-stage design. In the first stage, 17 patients were to be enrolled, and best response noted. If three or more responses were observed (defined as CR, PR, or SD for 12 weeks or more) among the 17 patients, the study would enroll an additional 16 patients for a total of at least 33 evaluable patients. As previously disclosed, this initial endpoint was met after six evaluable patients were enrolled. The primary objective of the trial was to determine the CBR of intravenous multiple doses of REOLYSIN in combination with gemcitabine in patients with advanced or metastatic pancreatic cancer. The secondary objectives were to determine PFS, and to determine the safety and tolerability of REOLYSIN when administered in combination with gemcitabine.

A copy of the poster presentation will be available on the Oncolytics website at: View Source

On July 6, 2015 ImmunoCellular Therapeutics reported the establishment of an agreement with Novella Clinical (Novella), to conduct the phase 3 registration trial of ICT-107 in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, JUL 6, 2015, View Source [SID:1234506167]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Novella is a full-service, global clinical research organization (CRO) providing clinical trial services to small to mid-sized oncology companies. The ICT-107 phase 3 trial will include approximately 120 clinical sites in the US, Europe and Canada, and will recruit about 400 patients with newly diagnosed glioblastoma. ImmunoCellular anticipates initiating the phase 3 trial in the fourth quarter of 2015.

Know more, wherever you are:
Latest on Brain Cancer, book your free 1stOncology demo here.

"Establishing this agreement with Novella Clinical moves us one more critical step forward in the implementation of our phase 3 ICT-107 registrational trial," said Andrew Gengos, ImmunoCellular Chief Executive Officer. "Novella’s special expertise in oncology clinical trials, combined with their strong international network, experience working with oncology cooperative groups, and reputation for high quality, efficiency and cost-effectiveness, make them an excellent partner for our ICT-107 program. We are rapidly building the infrastructure for our phase 3 program and remain on track to initiate the trial later this year."

Novella’s President Richard Staub added, "We are proud and very pleased to be selected to support this proprietary oncology immunotherapy platform for glioblastoma. We look forward to working alongside ImmunoCellular to navigate the development and successful execution of this pivotal program to ultimately benefit patients."

On July 6, 2015 ArQule reported interim data from an ongoing investigator-initiated Phase 2 clinical trial with tivantinib in combination with cetuximab in patients with MET-High, KRAS wild-type metastatic colorectal cancer (CRC) NCT01892527 who recently progressed on anti-EGFR antibodies (Press release, ArQule, JUL 6, 2015, View Source [SID:1234506164]). These data were presented on Friday, July 3rd at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) World GI 2015 (abstract number O-008) by Dr. Lorenza Rimassa, MD, Deputy Director, Medical Oncology Unit at Humanitas Cancer Center, in Rozzano (Milan, Italy).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Considering that in CRC objective response rate (ORR) often correlates with overall survival (OS) benefit, the preliminary results obtained combining tivantinib with cetuximab are encouraging," said Dr. Rimassa. "Since all patients enrolled in this trial were MET-High and had recently progressed on a combination regimen including cetuximab or panitumumab, the data may support the hypothesis that MET inhibition can reverse resistance to EGFR inhibitors as well as the need for rigorous tissue collection procedures at enrollment to allow for a more robust correlative outcome assessment related to the MET pathway."

The primary endpoint of the trial is ORR in the biomarker defined population. Secondary study endpoints are progression-free survival (PFS), overall survival (OS) and safety. The ESMO (Free ESMO Whitepaper) World GI presentation included data from 21 patients enrolled in Stage 1 of this trial. One patient, still on therapy, experienced a complete response (CR) and 2 patients experienced durable confirmed partial responses (PRs). Stable disease was observed in 8 patients, including 2 short duration PRs, for an overall Disease Control Rate (CR + PR + SD) of 52.4%. Having met the Stage 1 endpoint (≥2 confirmed responses), the trial continued to Stage 2 and has recently completed enrollment.

Adverse events were in line with those historically reported, including skin toxicity attributed to cetuximab, and neutropenia attributed to tivantinib. Neutropenia was addressed timely with growth factors and dose adjustments.

The trial is a 2-stage, investigator-initiated study testing tivantinib plus cetuximab after recent progression on anti-EGFR antibodies. The trial is coordinated by the Humanitas Cancer Center in Milan, Italy. Stage 1 enrolled 21 patients, and Stage 2 recently completed enrollment of 20 additional patients. Final results from the 41 patients enrolled are expected by the end of 2015.

About Colorectal Cancer (CRC)

Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. and is the third most common cancer in men and women. According to the National Cancer Institute, it is estimated that more than 132,000 new cases of colorectal cancer will be diagnosed in 2015, and an estimated 49,700 deaths from the disease will occur this year. The estimated incidence rate was 42.4 per 100,000 people during the period 2008-2012.

About MET and tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in Phase 2 and Phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in the tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, 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.

On July 6, 2015 Paoli Calmettes Institute (IPC) reported it has initiated a collaboration with Innate Pharma to conduct translational research aimed at identifying specific populations of patients with hematological cancers who may benefit most from treatment with Innate Pharma’s novel proprietary antibodies, and to identify associated biomarkers (Press release, Innate Pharma, JUL 6, 2015, View Source [SID:1234506163]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Nicolai Wagtmann, Chief Science Officer of Innate Pharma, said: "This agreement strengthens our translational research capabilities, at the core of our drug development process. IPC is a leading center in hematology-oncology with deep understanding in immunology and capabilities in immune monitoring. Early-stage testing of Innate Pharma’s promising antibodies on patient samples will greatly optimize subsequent clinical development by better identifying the most relevant indications, patient populations and biomarkers".

Know more, wherever you are:
Latest on Drug Target in Oncology, book your free 1stOncology demo here.

Pr. Patrice Viens, Chief Executive Officer of IPC, stated that "This new R&D collaboration with Innate Pharma further expands a long-lasting relationship which started with lirilumab, a fully human monoclonal antibody blocking the interaction between Killer-cell immunoglobulin-like receptors (KIR) on NK cells with their ligands on tumor cells. IPC conducted the "first-in-man study" of lirilumab and continues to be involved in the development of this drug. IPC and Innate Pharma are also involved in other partnerships within the frame of the Marseille SIRIC* and of Marseille Immunopole **".

The collaboration will operate under the direction of Pr. Daniel Olive, Head of the Immunity and Cancer research team and of the immune monitoring platform at IPC, and Pascale André, Senior Director, R&D, at Innate Pharma. It will also involve drug-discovery research teams and experts in translational research at IPC, including Pr. Norbert Vey and Pr. Anthony Gonçalvès, and other scientists with expertise in converting promising drug discoveries into clinical treatments for cancer patients.

Under the terms of the collaboration agreement, IPC will test Innate Pharma’s new therapeutic antibodies in immuno-oncology using IPC’s extensive biological resource collection. Innate Pharma’s antibodies are designed to block immune checkpoints, one of the most promising classes of drugs in oncology. These immune checkpoints interfere with the natural defense mechanisms of our immune system against cancer and regulate immunosuppressive mechanisms. Their blockade can unleash the patient’s immune system to recognize and eliminate cancer cells. However, only a fraction of patients respond to current immune checkpoint inhibitors, and identifying the population of patients most likely to respond to various checkpoint blockers would be of great interest. This R&D collaboration will facilitate the development of novel therapeutic antibodies by identifying the best suited patient population and indications for a given drug.