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Oncolytics Biotech® Announces Positive Clinical Trial Results for Pelareorep in Patients with KRAS Mutant Metastatic Colorectal Cancer for Presentation at ESMO 2018

On October 22, 2018 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus turning cold tumors hot, reported positive clinical trial results for pelareorep in the treatment of patients with KRAS mutant metastatic colorectal cancer. Patients receiving treatment with the recommended phase 2 dose (RPTD) of pelareorep ("Reo") in combination with FOLFIRI/B (irinotecan, fluorouracil, leucovorin, plus bevacizumab) had progression free survival (PFS) of 65.6 weeks and an overall survival (OS) of 107.5 weeks, which exceeded expectations when compared to historical data (Press release, Oncolytics Biotech, OCT 22, 2018, View Source [SID1234530638]). Engagement of the adaptive immune system was also noted, suggesting that pelareorep promotes an inflamed tumor phenotype. This clinical data was presented at the annual European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, taking place October 19-23 in Munich.

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"The results from the six patients in this study receiving the recommended phase two dose demonstrate a more than doubling of overall survival based on previous phase three studies using FOLRIRI with anti-VEGF therapy," said lead author, Dr. Sanjay Goel, M.D., Department of Medical Oncology, Montefiore Medical Center. "These favorable results lend support to pelareorep as a potential treatment option in this patient population with metastatic disease, that has shown disease progression on current standard-of-care chemotherapy."

Poster Presentation at ESMO (Free ESMO Whitepaper) 2018
The poster titled "Dose finding and safety study of Reovirus (Reo) with irinotecan/fluorouracil/leucovorin/bevacizumab (FOLFIRI/B) in patients with KRAS mutant metastatic colorectal cancer (mCRC): Final Results", was presented yesterday at ESMO (Free ESMO Whitepaper). This phase 1 dose escalation study enrolled 36 patients with oxaliplatin refractory KRAS mutant metastatic colorectal cancer. The trial was designed to determine the maximum tolerated dose and a RPTD.

Highlights from the Poster:
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Of the six patients receiving the RPTD, three had a partial response (50%) and the median PFS and OS were 65.6 weeks and 107.5 weeks, respectively, exceeding expectations when compared to historical data
•
Reovirus administration is marked by activation of cytotoxic T-cells and rapid maturation of dendritic cells
•
Reovirus is safe and well tolerated in combination with FOLFIRI and Bevacizumab

"This impressive survival data coupled with the engagement of the adaptive immune system reinforce both the data from our metastatic breast cancer program and the increasing interest in studies combining pelareorep with immune checkpoint inhibitors," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech. "The results presented at ESMO (Free ESMO Whitepaper) suggest the clinical utility of pelareorep may expand into multiple indications, including breast, colon and other cancers, and support our clinical development program."

Additional details can be found on the company website: View Source

References:
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Journal of Oncology, Vol. 30, Number 28, October 1, 2012
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The Lancet, Vol. 16, May 2015
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The Lancet, Vol. 14, January 2013

About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

Moffitt Cancer Center and Anixa Biosciences Announce Completion of Pre-IND Meeting with FDA for CAR-T Therapy

On October 22, 2018 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on using the body’s immune system to fight cancer, reported that it, along with its partner Moffitt Cancer Center (MCC), completed a pre-IND (Investigational New Drug) meeting with the US FDA on October 16, 2018 (Press release, Anixa Biosciences, OCT 22, 2018, View Source [SID1234530498]).

The meeting was focused on discussing the development of a novel CAR-T therapy that takes advantage of specific hormone–hormone receptor biology to address ovarian cancer. Approved CAR-T therapies and others in clinical trials have demonstrated dramatic results for certain hematological cancers (also known as liquid tumors), but to date there has not been any meaningful demonstration of CAR-T efficacy against solid tumors in humans. Anixa and MCC hope their therapy will demonstrate success with ovarian cancer patients due to their unique hormone–hormone receptor approach. If successful in ovarian cancer, this approach may create a new pathway for CAR-T development against many other solid tumors.

Dr. Amit Kumar, President and CEO of Anixa Biosciences said, "It is very consequential that we have begun a dialogue with the FDA. The pre-IND meeting answered a number of questions we presented to the FDA and clarified some matters, providing us with a good understanding of the design for the clinical trial in our IND application. Further, we identified the final experiments needed to complete our IND filing. We are in the process of completing these experiments, after which we will file our IND application. The IND, after review and approval by the FDA, will enable us to test our therapy in ovarian cancer patients. Assuming the FDA approves our IND, we anticipate beginning the trial as early as the summer of 2019."

Dr. Jose Conejo-Garcia, chair of the Department of Immunology at Moffitt Cancer Center, the inventor of the technology, and the Principal Investigator of the team developing the therapy added, "Our CAR-T is the first in human therapy of its kind and the feedback we received from the FDA was quite helpful. We are excited to be so close to bringing our investigational therapy to ovarian cancer patients."

Corvus Pharmaceuticals Announces New Data on Adenosine Gene Signature Biomarker Associated with Patient Response to CPI-444 at European Society for Medical Oncology (ESMO) 2018 Congress

On October 22, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported new data on a biomarker associated with patient response to therapy with CPI-444, an adenosine receptor antagonist. This "adenosine gene signature" has the potential to be used as a predictive biomarker for patient selection in future clinical studies of CPI-444 and other therapies targeting the adenosine pathway, including CPI-006 (Press release, Corvus Pharmaceuticals, OCT 22, 2018, View Source [SID1234530341]). The biomarker data was presented today in a poster discussion session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany, by Stephen Willingham Ph.D., a senior scientist at Corvus.

CPI-444, Corvus’ lead product candidate, is a selective and potent inhibitor of the adenosine A2A receptor. It is currently being evaluated in clinical trials in patients with various solid tumors as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody. CPI-006 is a humanized monoclonal antibody directed against CD73. It is currently being evaluated in an early-stage, three-arm clinical trial in patients with a variety of solid tumors as a single agent, in combination with CPI-444, and in combination with pembrolizumab, an anti-PD-1 antibody.

"The gene expression profiles associated with the adenosine pathway have been shown to lead to the secretion of various inflammatory cytokines and chemokines that recruit suppressive myeloid cells and dampen T-cell function. The biomarker data presented at ESMO (Free ESMO Whitepaper) demonstrates that in vitro and in vivo treatment of human immune cells with CPI-444 blocks the expression of this adenosine gene signature, confirming its mechanism of action," said Dr. Willingham. "The expression of the adenosine gene signature has been shown to correlate with tumor regression in our ongoing Phase 1/1b trial of CPI-444 for the treatment of patients with renal cell carcinoma (RCC). In the trial, patients with high expression of the adenosine gene signature were more likely to have tumor regression than those patients with low expression (p<0.008). Our data, together with other recently published data, indicate that tumors with an adenosine-rich environment are resistant to therapy with anti-PD-(L)1 antibodies, and provide support for the addition of CPI-444 to these therapies to enhance efficacy."

"Our discovery of the adenosine gene signature biomarker represents a major step forward for therapies based on blockade of the adenosine pathway," said Richard A, Miller M.D., an oncologist; co-founder, president and chief executive officer of Corvus. "This biomarker could potentially be used in the future to select patients most likely to benefit from adenosine blockade with either CPI-444 or antibodies that inhibit adenosine production, such as CPI-006. These data, as well as our ongoing trials with CPI-444 and CPI-006, continue to advance the field and confirm the mechanism of action of CPI-444 and adenosine antagonism. Additional data on these programs will be presented at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November."

About CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.

About CPI-006
CPI-006 is a potent humanized monoclonal antibody that reacts with the active site of CD73, blocking the conversion of AMP to adenosine. In vitro studies of CPI-006 have shown it is capable of substantially inhibiting the production of adenosine by blocking the CD73 enzyme.

Taiho and Servier Announce Positive Results from LONSURF® (trifluridine/tipiracil) Study Presented at ESMO 2018 Congress and Published in The Lancet Oncology

On October 22, 2018 Taiho Pharmaceutical Co., Ltd. and Servier reported that the clinical data from the pivotal Phase III (TAGS) trial were presented at the ESMO (Free ESMO Whitepaper) 2018 Congress held in Munich, Germany, from October 19 to 23 (Press release, Taiho, OCT 22, 2018, View Source [SID1234530335]). The study results were simultaneously published in The Lancet Oncology. Based on the results, Servier filed a new application for an additional indication for gastric cancer to the European Medicines Agency (EMA) for LONSURF.

The TAGS trial evaluates LONSURF (trifluridine/tipiracil, TAS-102) versus placebo and best supportive care in patients with heavily pretreated metastatic gastric/gastroesophageal junction (GEJ) cancers who have progressed or are intolerant to previous lines of therapy. The trial met its primary endpoint of prolonged overall survival (OS) and secondary endpoint measures of progression-free survival (PFS) consistently supported the OS results, as well as continued to demonstrate LONSURF’s predictable safety and tolerability profile. TAGS, a phase 3, randomised, double-blind study of trifluridine/tipiracil (TAS-102) versus placebo in patients with refractory metastatic gastric cancer (Abstract #LBA25), data were presented by Hendrik-Tobias Arkenau, MD, PhD, from the Sarah Cannon Research Institute UK at the ESMO (Free ESMO Whitepaper) 2018 Congress during an oral session on Sunday, October 21 at 11:10 AM CEST.

In the TAGS trial, patients treated with LONSURF showed a clinically meaningful and statistically significant improvement in OS compared with placebo, a 31 percent risk reduction of death (HR 0.69), which translated into a prolongation of median survival of 2.1 months (5.7 months for trifluridine/tipiracil versus 3.6 months for placebo). In addition, LONSURF demonstrated a statistically significant improvement in PFS and time to deterioration of ECOG performance status versus placebo, as well as a predictable and manageable safety profile consistent with that previously reported in patients with metastatic colorectal cancer (mCRC). Taiho Pharmaceutical and Servier remain committed to making further contributions to patients and to medical practitioners engaged in the treatment of cancer.

About TAGS
The TAGS (TAS-102 Gastric Study) trial is a Taiho-sponsored pivotal Phase III multinational, randomized, double-blind study evaluating LONSURF (trifluridine/tipiracil), also known as TAS-102, plus best supportive care (BSC) versus placebo plus BSC in patients with metastatic gastric cancer, including gastroesophageal junction cancer, refractory to standard treatments. The primary endpoint in the TAGS trial is overall survival (OS), and the main secondary endpoint measures include progression-free survival (PFS), and safety and tolerability, as well as quality of life.

The TAGS trial aimed to enroll 500 adults 18 years and older, with metastatic gastric cancer who had previously received at least two prior regimens for advanced disease. The trial enrolled 507 subjects and was conducted in Japan, the United States, the European Union, Russia, Belarus, Israel, and Turkey.

For more information on the TAGS trial, please visit www.ClinicalTrials.gov (View Source). The ClinicalTrials.gov Identifier is NCT02500043.

About Gastric Cancer
Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related death (after lung and liver cancer), with an estimated 723,000 deaths annually1 . In Japan, gastric cancer is
the most common cancer and the third most common cause of cancer-related death (after lung and colorectal cancer), causing around 45,000 deaths annually2
.
In recent years, the outcome for gastric cancer has improved remarkably, and survival has increased dramatically over the past 10 years. As cancer progresses, however, numerous complications can limit the usable drugs and preclude intensive chemotherapy. Prolonging survival and relieving symptoms in late-stage treatment for metastatic gastric cancer are issues for which it is thought important to increase the options for new therapeutic drugs. At present, nivolumab and irinotecan are recommended in Japan as the standard third line treatment for metastatic
gastric cancer.

About LONSURF
LONSURF (trifluridine/tipiracil) is an oral anticancer drug, which utilizes the combination of trifluridine (FTD) and tipiracil (TPI), whose dual mechanism of action is designed to maintain clinical activity and differs from conventional fluoropyrimidines. FTD is an antineoplastic nucleoside analogue, which is incorporated directly into the DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.

In Japan, Taiho Pharmaceutical has been marketing LONSURF for the treatment of unresectable advanced or recurrent colorectal cancer since 2014. In the United States, beginning in 2015, Taiho Oncology, Inc., a U.S.
subsidiary of Taiho Pharmaceutical, began marketing the drug for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

In 2015, Taiho Pharmaceutical and Servier entered into an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico and Asia. In parts of Asia outside of Japan, Taiho Pharmaceutical’s business partner TYY Biopharm launched LONSURF in
Taiwan in July 2018, and Jeil Pharmaceutical is preparing to bring the drug to market in South Korea.

As of October 2018, LONSURF has been approved as a treatment for mCRC in 61 countries and regions worldwide.

Intensity Therapeutics Announces Preliminary Data from Clinical Study of INT230-6 in Advanced Solid Tumors

On October 22, 2018 Intensity Therapeutics, Inc., a clinical-stage biotechnology company developing proprietary immune cell-activating cancer treatments, reported preliminary data from a Phase 1/2 clinical study demonstrated that INT230-6, the Company’s novel lead product candidate designed for direct intratumoral injection, was well tolerated in patients with advanced solid tumors (Press release, Intensity Therapeutics, OCT 22, 2018, View Source [SID1234530321]). The data were presented in a poster session on Saturday at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany.
INT230-6 is comprised of two proven, potent anti-cancer agents and a unique molecule that causes rapid drug dispersion throughout tumors and diffusion into cancer cells. In preclinical studies, INT230-6 demonstrated the ability to thoroughly saturate and kill injected tumors and induce an adaptive immune response that attacks non-injected tumors.

"We are pleased to share the first clinical data emerging from Intensity’s study evaluating INT230-6 in patients with different types of solid tumors. This early data indicates that INT230-6 can be safely injected into several different types of superficial and deep tumors, and the vast majority of the active components stay inside the tumor," said Ian B. Walters, MD, Chief Medical Officer of Intensity.

The presenting author and a study investigator, Anthony El-Khoueiry, MD, Associate Professor of Clinical Medicine and phase I program director at the University of Southern California Norris Comprehensive Cancer Center, said, "We have treated 20 patients in the study thus far, and the intratumoral injections of INT230-6 have been well tolerated. Most patients experienced mild to moderate transient local pain and swelling. Even at low doses, we are seeing some anti-tumor effects in injected tumors, as well as some evidence of immune activation in the blood. There are also early signs of anti-tumor effects in distal untreated tumors."

Dr. Walters added, "The study will continue to enroll patients with difficult-to-treat tumors as we explore higher doses. We look forward to adding more North American sites, as well as new centers outside the U.S. and Canada. In addition, we plan to move into combination arms with an anti-PD-1 antibody and begin Phase 2 expansion cohorts next year."

About INT230-6

INT230-6, Intensity’s lead product candidate designed for direct intratumoral injection, is comprised of two proven, potent anti-cancer agents and a penetration enhancer molecule that helps disperse the drugs throughout tumors and diffuse into cancer cells. INT230-6 is being evaluated in a Phase 1/2 clinical study (NCT03058289) in patients with various advanced solid tumors. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor kill and recruitment of dendritic cells to the tumor micro-environment that induced anti-cancer T-cell activation. Treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responder animals with long-term, durable protection from multiple re-inoculations of the initial cancer and resistance to other cancers. In mouse models, INT230-6 has shown strong synergy with checkpoint blockage, including anti-PD-1 and anti-CTLA4 antibodies. INT230-6 was discovered from Intensity’s DfuseRxSM platform.

About the Phase 1/2 Clinical Study

INT230-6 is being evaluated in a Phase 1/2 clinical study in patients with different types of advanced solid tumor malignancies. The study’s primary objective is to assess the safety and tolerability of multiple intratumoral doses of INT230-6. Secondary assessments are the measurement of injected and bystander tumor responses, and determination of the systemic pharmacokinetic profile of multiple doses of INT230-6’s drug substances after single and then multiple intratumoral injections. Exploratory analysis will characterize patient outcome, as well as evaluate various tumor and anti-tumor immune response biomarkers that may correlate with response. The study includes several adaptive components that will allow for adjustments in patient groups, dosing schedule and dose volumes administered. Data will be used to assess the progression free and overall survival in patients receiving INT230-6. For more information, please visit www.clinicaltrials.gov (NCT03058289).