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Polaris Group Announces Treatment of First Patient in Phase 1 Study of ADI‑PEG 20 Plus Cytarabine in Older Patients with Acute Myeloid Leukemia

On January 20, 2017 Polaris Group reported that the first patient has been dosed in its phase 1 trial of ADI‑PEG 20 in combination with low-dose cytarabine for the treatment of acute myeloid leukemia (AML) in older patients (Press release, Polaris Pharmaceuticals, JAN 20, 2017, View Source [SID1234526287]). In addition to a global phase 2/3 study in malignant plural mesothelioma featuring ADI‑PEG 20 in combination with pemetrexed and cisplatin, Polaris Group is currently conducting multiple phase 1 clinical trials, including ADI‑PEG 20 in combination with pemetrexed and cisplatin in non-small cell lung carcinoma, glioblastoma, and uveal melanoma, in combination with gemcitabine and paclitaxel in pancreatic cancer and in combination with FOLFOX in hepatocellular carcinoma, gastric cancer, and colorectal cancer.

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"We hope that the addition of ADI‑PEG 20, which has a different mechanism of action than cytarabine, will result in both safety and added efficacy", said John Bomalaski, M.D., Executive Vice President, Medical Affairs at Polaris Pharmaceuticals, Inc.

About ADI‑PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

The CRT Pioneer Fund and Cancer Research UK’s Manchester Institute nominate cancer drug candidate

On January 20, 2017 The Cancer Research Technology Pioneer Fund LP (CPF) reported that it will further develop a promising class of cancer drugs called RET inhibitors, through a collaboration with the Cancer Research UK Manchester Institute Drug Discovery Unit*, at The University of Manchester (Press release, Cancer Research Technology, 20 20, 2017, View Source [SID1234523171]).

A potential drug candidate identified through the collaboration has entered preclinical studies, the stage necessary to enable an investigational new drug (IND) application. These studies ensure the drug is safe to be given to patients. If the studies are successful the experimental drug will be funded through early clinical trials.

Ian Miscampbell, managing partner of Sixth Element Capital which manages the CPF, said: "We’re delighted to announce this significant project milestone. And the further investment we’ve made will pave the way for a potential new cancer drug to be taken into phase I clinical trials. If the first studies are successful we’ll seek industry partners to further develop and commercialise these drugs."

The RET inhibitor programme was led by scientists at Cancer Research UK’s Manchester Institute. Investment by the CPF in 2014 built on the research of the group and enabled the acceleration of the programme.

The RET gene plays a critical role in the development of medullary thyroid cancer. Up to two percent of non-small cell lung adenocarcinomas – originating in the mucus-secreting cells lining the airways – have RET mutations. The project aims to discover novel compounds targeting the RET gene in a specific population of patients.

Dr Donald Ogilvie, head of drug discovery at the Cancer Research UK Manchester Institute at The University of Manchester, said: "We’re pleased to work with the CRT Pioneer Fund to accelerate progress on the exciting RET inhibitors discovered by Cancer Research UK scientists at our Institute.

"Lung cancer can be difficult to treat successfully. As part of the Cancer Research UK Lung Cancer Centre of Excellence, we’re determined to get new lung cancer treatments to patients. Identifying this candidate drug molecule offers the potential to help boost survival from this disease."

Dr Phil L’Huillier, Cancer Research Technology’s director of business development, said: "It’s fantastic news that CRT’s Pioneer Fund has helped speed up this important research from the lab to potentially benefit patients. It’s essential that we bridge the innovation gap in UK drug discovery, so that patients can quickly get the promising new drugs being developed in Cancer Research UK labs and elsewhere around the world."

PRIMA BIOMED COMMENCES RANDOMISED PHASE IIb CLINICAL TRIAL FOR IMP321 IN BREAST CANCER

On January 20, 2016 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima" or the "Company") reported the first patient has been dosed as part of the enlarged randomised phase of its AIPAC Phase IIb clinical trial for IMP321 in metastatic breast cancer (Press release, Prima Biomed, JAN 20, 2017, View Source [SID1234517473]).

The randomised phase of AIPAC (Active Immunotherapy PAClitaxel) will see half of the 226 patients receiving paclitaxel plus a placebo and half receiving paclitaxel in conjunction with IMP321. This follows the Dose Escalation Committee approval of the 30 mg dosage level for IMP321 and commencement of the randomised study on December 30, 2016.

Prima’s Chief Medical Officer, Dr Frédéric Triebel, said: "We are pleased to have dosed the first patient in the randomised and double-blind Phase of the AIPAC trial. Following positive interim data released in December and the 30mg dosage approval, we are now focused on screening and enrolment of the enlarged patient cohort across our European centres."

About IMP321
IMP321, a first-in-class Antigen Presenting Cell (APC) activator based on the immune checkpoint target LAG-3, represents one of the first proposed active immunotherapy drugs in which the patient’s own immune system is harnessed to respond to tumour antigenic debris created by chemotherapy. As an APC activator IMP321 boosts the network of dendritic cells in the body that can respond to tumour antigens for a better anti-tumour CD8 T cell response.

OncoMed Initiates Enrollment of Phase 1b Clinical Trial of Brontictuzumab for the Treatment of Metastatic Colorectal Cancer Patients

On January 20, 2017 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported dosing of the first patient in a Phase 1b clinical trial of brontictuzumab (anti-Notch1, OMP-52M51) plus chemotherapy in patients with metastatic colorectal cancer (Press release, OncoMed, JAN 20, 2017, View Source [SID1234517470]).

The Phase 1b trial is intended to determine the maximum-tolerated dose of brontictuzumab in combination with trifluridine/tipiracil (Lonsurf). The Phase 1b trial is designed to assess safety, preliminary efficacy and immunogenicity, as well as predictive and pharmacodynamics biomarkers. Metastatic colorectal cancer patients who have received at least two prior lines of therapy will be enrolled in the dose-escalation portion of the trial, and once a maximum tolerated dose is identified, additional patients whose tumors test high for the activated form of Notch1 will be enrolled in an expansion cohort.

"Brontictuzumab targets Notch1, a key receptor in the Notch pathway, and preclinical data suggest that elevated Notch1 gene expression appears to be an oncogenic driver in a number of tumor types, including colorectal cancer," said Robert Stagg, Pharm.D., OncoMed’s Senior Vice President, Clinical Research and Development. "In this Phase 1b trial, we expect to determine the safety and optimal therapeutic index of brontictuzumab in combination with chemotherapy, assess preliminary efficacy and explore the correlation of biomarker status and anti-tumor responses."

About Brontictuzumab
Brontictuzumab (anti-Notch1, OMP-52M51) blocks signaling of Notch, an important cancer stem cell pathway implicated in chemoresistance, tumor angiogenesis and stem cell self-renewal, proliferation and differentiation. Notch1 signaling is prevalent in several solid tumor types, including certain breast, esophageal, colorectal, gastric, pancreatic and small cell lung cancers, as well as adenoid cystic carcinoma and cholangiocarcinoma. Single-agent anti-tumor activity was observed in OncoMed’s Phase 1a dose escalation study of brontictuzumab in patients with certain advanced solid tumors, particularly in biomarker-defined patients whose tumors tested positive for overexpression of the activated form of Notch1. Brontictuzumab was generally well tolerated, with the most common adverse event being manageable diarrhea.1

OncoMed retains the worldwide rights to develop brontictuzumab.

Mateon Therapeutics to Present Data on Study OX4218 in Neuroendocrine Tumors at ASCO Gastrointestinal Cancers Symposium

On January 20, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported the presentation of final data from Study OX4218 in patients with neuroendocrine tumors (NETs) at a poster session at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium being held today in San Francisco (Press release, Mateon Therapeutics, JAN 20, 2017, View Source [SID1234517469]).

Study OX4218 was a multi-center, open label, phase 2 clinical trial to investigate the safety and activity of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid (PNETs or GI-NETs) with elevated biomarkers. Following patients’ completion of Study OX4218, patients were eligible to enroll in Study OX4219, a long term extension study, if they achieved a biomarker or symptom response. In OX4218 patients were treated with CA4P 60 mg/m2 on Days 1, 8, and 15 of a 21-day cycle for 3 cycles, and in OX4219 patients received CA4P maintenance on Day 1 of a 21-day cycle until disease progression or up to one year.

A total of 18 patients were enrolled in OX4218. One patient (6%) experienced significant symptomatic improvement as measured by ECOG Status and had a partial response per investigator-assessed RECIST and an additional 7 patients (39%) had stable disease. In addition, a majority of patients (53%) experienced an improvement in patient-reported quality of life. A statistically significant mean change in biomarkers from baseline, the primary endpoint of the study, was not achieved in OX4218 due to the small sample size along with a high intra- and inter-patient variability observed in the biomarkers. A total of 7 patients were enrolled in OX4219, of which 5 patients (71%) had stable disease, including one that continued for 14 months. The partial response and stable disease analyses, as well as other measures from the trial, suggest that CA4P monotherapy has activity in this indication.

"The results of OX4218 and OX4219 confirm that CA4P monotherapy has efficacy in the indications studied, as we have seen with the investigational drug in a number of other monotherapy trials," said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "However, we believe that the efficacy of CA4P only becomes compelling when it is used in combination with an anti-angiogenic agent, due to the complementary mechanisms of action for the two agents. Based on the evidence of efficacy observed in this trial, plus an understanding of the benefits of combination therapy, a lead investigator in this trial is sponsoring a 20 patient study in NETs using CA4P in combination with everolimus (AFINITOR, marketed by Novartis), an anti-angiogenic agent which is already approved and commonly used in this indication."

Overall CA4P monotherapy was well tolerated. Treatment related adverse events were reported in 77% of subjects. The most common Grade 3-5 AEs ( > 10%) included: anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases. One Grade 5 adverse event, carcinoid syndrome, was reported and attributed to the underlying disease.