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Phase II Clinical Study Obatoclax (GX15-070) for SCLC


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http://www.medicalnewstoday.com/articles/141223.php

ARTICLE:

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Gemin X Pharmaceuticals, a clinical stage biopharmaceutical company developing novel, targeted cancer therapeutics, today announced the initiation of a Phase 2 clinical trial of its lead product candidate obatoclax (GX15-070) for the treatment of patients with extensive-stage small cell lung cancer (SCLC). In this multi-center, randomized, open-label Phase 2 study, clinical effect of a combination of carboplatin, etoposide and obatoclax (the "CEO" regimen) will be compared to the standard chemotherapeutic therapy of carboplatin and etoposide alone (the control arm) in patients with SCLC. The primary endpoint of the study, expected to enroll approximately 150 patients with SCLC, is comparison of overall response rate (ORR) for the obatoclax-containing arm versus the control arm. Secondary endpoints include comparison of progression free survival (PFS) and overall survival (OS), as well as safety.

"We are very pleased to begin this Phase 2 study in small cell lung cancer in accordance with our broad development plan for obatoclax, which also includes Phase 2 trial initiations this year in acute lymphoblastic leukemia and systemic mastocytosis," said Glenn Gormley, M.D., Ph.D., President and Chief Executive Officer at Gemin X. "We are encouraged by the striking synergy observed between obatoclax and carboplatin and etoposide in preclinical studies and by the dramatic responses seen to-date in the vast majority of SCLC patients in our ongoing Phase 1b trial. It is our hope that obatoclax's differentiated mechanism will lead to substantial improvements in response to treatment, tolerability and survival for these cancer patients."

The ongoing Phase 1b dose-escalation portion of this study established safety and identified the recommended dose for obatoclax, when administered in combination with standard doses of carboplatin and etoposide as both front-line and second-line therapy. This Phase 1b trial showed a significant response rate for the small cell lung cancer patients dosed with the obatoclax-chemotherapy combination after two cycles of therapy, based on RECIST measures.

In the Phase 2 study, each patient in the obatoclax combination arm will receive three-hour infusions on three consecutive days of dosing every three weeks over six treatment cycles (provided there is no evidence of disease progression or intolerability). Patients enrolled into the obatoclax combination arm of the study and who have not progressed after six treatment cycles will continue to receive obatoclax alone as maintenance therapy after completion of combination chemotherapy. The trial is expected to be completed by the fourth quarter of this year.

"The Phase 1 data using obatoclax in combination with carboplatin and etoposide demonstrated how these drugs can be combined safely, and the early efficacy data are promising. Oncologists have been looking for a combination that could improve on the results with carboplatin and etoposide in small cell lung cancer for many years, and the Phase 2 randomized study that has just begun will provide a good test of just what the addition of obatoclax can do," said Alberto A. Chiappori, M.D., Associate Professor at the H. Lee Moffitt Cancer Center & Research Institute. "Based on the fact that small cell lung cancers often express prosurvival Bcl-2 family proteins, and that the combination with obatoclax has demonstrated synergy in vitro, this study of obatoclax combined with carboplatin and etoposide is an exciting opportunity for improving the treatment of small cell lung cancer."

About Obatoclax

Obatoclax, Gemin X's potential first-in-class small molecule antagonist of Bcl-2, is specifically designed to inhibit all relevant members of the Bcl-2 family of proteins, including the dominant member, Mcl-1. Inhibition of Mcl-1 and other Bcl-2 related proteins enhances cancer cell death by facilitating apoptosis and/or autophagy. These proteins have been shown to have a pro-survival effect in malignant cells; thus their inhibition by obatoclax could increase the activity of the drug's tumor killing effect. Obatoclax has been shown to activate cancer cell death in vitro, to exhibit anti-tumor activity in animal models, and to enhance the effects of chemotherapy in various models including with the drugs carboplatin and etoposide. It has also shown single-agent biological and clinical activity in Phase 1 studies in a variety of cancer indications. Further, obatoclax has demonstrated an early ability to mechanistically evade the resistance built up by cancer cells to traditional chemotherapeutic agents.

Gemin X's global development plan for obatoclax is focused on diseases marked by up-regulation of Mcl-1, including small cell lung cancer (in combination with carboplatin and etoposide), refractory acute lymphoblastic leukemia (in combination with dexamethosone) and systemic mastocytosis (as a single agent).

Small Cell Lung Cancer

Small cell is an aggressive form of lung cancer, and accounts for about 15% of all lung cancer cases, according to the American Cancer Society. Chemotherapy alone or combined with radiation is the usual treatment of choice for small cell lung cancer. According to the Journal of Clinical Oncology, the median survival time is approximately nine to 12 months with currently available therapies and the five-year survival rate for patients with extensive stage SCLC is less than 1%. Improved diagnostic and surgical techniques and novel combination therapies that can further extend patient survival are desperately needed to positively impact these outcomes.

About Gemin X Pharmaceuticals

Gemin X is developing first-in-class cancer therapeutics based on reinitiating programmed cell death, or apoptosis, inducing cancer cell self-digestion, or autophagy, and the inhibition of metabolism in cancerous cells. Gemin X currently has several clinical development programs underway, including Phase 2 clinical trials for its lead product candidates obatoclax (GX15-070), an innovative pan Bcl-2 inhibitor, and GMX1777, a novel inhibitor of NAD+ synthesis, and preclinical studies for its Telomere Capping and SMAC Mimetic programs. Potential treatment indications for the full scope of pipeline programs span a broad range of hematological and solid tumors, including chronic lymphocytic leukemia (CLL), melanoma, small cell lung cancer (SCLC), refractory acute lymphoblastic leukemia (ALL) and systemic mastocytosis. Founded in 1998, Gemin X is privately held with drug development and executive headquarters in Malvern, Pennsylvania and drug discovery operations in Montréal, Canada.

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(Medical News Today, Lung Cancer; Cancer/Oncology, March 5, 2009)

Disclaimer:

The information contained in these articles may or may not be in agreement with my own opinions. They are not being posted with the intention of being medical advice of any kind.

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