At the recent AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer in Coronado, CA, many positive advances were presented, including a new study, which suggested that retreating non-small cell lung cancer (NSCLC) patients with AstraZeneca's Iressa (gefitinib) could have a beneficial effect, Phase II study results of ASA404 (vadimezan) in patients with either squamous or non-squamous NSCLC and preclinical results showing that Synta Pharmaceuticals' STA-9090 is active against 100 per cent of all NSCLC cell lines tested.
With regard to the gefitinib study, researchers evaluated 15 patients who were retreated with the drug after more than one cycle of chemotherapy for advanced or metastatic NSCLC. Among the six patients who had showed partial response (PR) with initial gefitinib treatment, two patients showed an additional PR and three continued to show stable disease (SD). Among the nine patients who showed SD with the initial gefitinib treatment, two patients showed PR and three showed SD. The overall disease control rate was 66.7 per cent.
Separately, ASA404 showed promise in patients with either squamous or non-squamous NSCLC. These results support ongoing Phase III studies of the drug in NSCLC. Under development by Novartis, which licensed the drug from Antisoma, ASA404 has a unique mechanism of action against a tumour's blood supply. The product has been shown to cause selective disruption of the established tumour vasculature, inhibition of tumour blood flow and tumour necrosis. This unique mechanism of action could provide an option for patients with either squamous or non-squamous NSCLC. Treatment options for patients with advanced-stage NSCLC are limited, particularly for those with squamous histology where some treatments exhibit limited efficacy or serious side effects.
Further, preclinical results showed that STA-9090, a potent, synthetic inhibitor of heat shock protein 90, demonstrated potent activity against 100 per cent of all NSCLC cell lines tested, including those with EGFr, HER2 or KRAS mutations, including the EGFr T790 mutation that is present in approximately 50 per cent of cases of erlotinib or gefitinib resistance. Synta is currently enrolling patients in a single-arm, open-label, single-agent, Phase II study of STA-9090 in patients with Stage IIIb or IV NSCLC, with patient cohorts defined by the genetic profile of their tumours.
STA-9090 potently inhibited cell proliferation in 24 out of 24 human NSCLC lines tested, irrespective of EGFr, HER2 or KRAS mutational status. In vivo, STA-9090 stopped tumour growth in both erlotinib-sensitive and -resistant NSCLC xenograft models. In addition, in a HER2-positive adenosquamous LC study, three out of four animals treated with STA-9090 experienced partial responses, as measured by MRI. Dr Vojo Vukovic, Chief Medical Officer of Synta, stated: "taken together, the in vitro and in vivo results presented at this conference demonstrate the potency, broad activity and safety profile of STA-9090, both as a single agent and in combination with taxanes in NSCLC."
Alice Rossiter
Editor, Cancer Drug News
Thursday, January 21, 2010
Wednesday, January 13, 2010
Advances in skin cancer R&D
The last week has seen notable advances in the field of skin cancer research and development, including the initiation of Plexxikon's pivotal Phase III trial of PLX4032 in patients with metastatic melanoma (MM), detailed results of Biofrontera's Phase III comparative study of BF-200 ALA for the treatment of actinic keratosis (AK) and a new study from Stanford University suggesting that an anti-inflammatory prescription drug can reduce the risk of a common skin cancer in humans.
Enrolment has been initiated and the first patient has been dosed in the pivotal Phase III trial of PLX4032, a novel, oral and highly-targeted drug that is designed to inhibit the BRAF cancer-causing mutation that occurs in approximately 50 per cent of melanomas. The randomised, controlled trial, called BRIM3 (BRAF Inhibitor in Melanoma), in previously-untreated patients is part of the planned registration programme for PLX4032. With some tumour shrinkage in nearly all mutation-positive melanoma patients, and 70 per cent of patients achieving at least 30 per cent tumour shrinkage in the company's most recent clinical study, PLX4032 has shown meaningful antitumour activity. BRIM3 is expected to enrol approximately 700 previously-untreated melanoma patients who will be randomised 1:1 with PLX4032 960mg twice daily or dacarbazine.
Separately, detailed results of Biofrontera's Phase III comparative study have confirmed the superiority of BF-200 ALA over Photocure's Metvix (methylaminolevulinate) for the treatment of AK. Patients were treated by photodynamic therapy, combining one of the test compounds or a placebo with a brief red light illumination. With different types of red light sources, BF-200 ALA on average erased all lesions in 78 per cent of the patients, whereas the registered comparator, methylaminolevulinate, only reached a complete healing rate of 64 per cent, and the placebo group of 17 per cent.
Further, according to researchers at Stanford University School of Medicine, a widely-available anti-inflammatory prescription drug can reduce the risk of a common skin cancer in humans. The scientists believe that although oral administration of celecoxib is associated with an increased risk of myocardial infarction and stroke in some people, it is possible that topical application could have a safer, protective effect for people prone to developing basal cell carcinomas (BCCs). The investigators dovetailed studies in mice with a randomised, double-blind, Phase II trial to reach their conclusions.
The researchers enrolled 60 people with a genetic predisposition to BCC in a three-year trial. Approximately half of the patients received celecoxib 200mg twice daily in a tablet format, while the others received a placebo. All patients were monitored at three-month intervals at one of four study sites for the development of new BCCs or the growth of previously-identified cancers. They found that, although both groups continued to develop new cancers during the study, oral celecoxib treatment decreased the growth of skin tumours by approximately 50 per cent, as compared to placebo, in participants who entered the trial with 15 or fewer BCCs. Celecoxib treatment also reduced the overall tumour burden in this group of patients.
Alice Rossiter
Editor, Cancer Drug News
Enrolment has been initiated and the first patient has been dosed in the pivotal Phase III trial of PLX4032, a novel, oral and highly-targeted drug that is designed to inhibit the BRAF cancer-causing mutation that occurs in approximately 50 per cent of melanomas. The randomised, controlled trial, called BRIM3 (BRAF Inhibitor in Melanoma), in previously-untreated patients is part of the planned registration programme for PLX4032. With some tumour shrinkage in nearly all mutation-positive melanoma patients, and 70 per cent of patients achieving at least 30 per cent tumour shrinkage in the company's most recent clinical study, PLX4032 has shown meaningful antitumour activity. BRIM3 is expected to enrol approximately 700 previously-untreated melanoma patients who will be randomised 1:1 with PLX4032 960mg twice daily or dacarbazine.
Separately, detailed results of Biofrontera's Phase III comparative study have confirmed the superiority of BF-200 ALA over Photocure's Metvix (methylaminolevulinate) for the treatment of AK. Patients were treated by photodynamic therapy, combining one of the test compounds or a placebo with a brief red light illumination. With different types of red light sources, BF-200 ALA on average erased all lesions in 78 per cent of the patients, whereas the registered comparator, methylaminolevulinate, only reached a complete healing rate of 64 per cent, and the placebo group of 17 per cent.
Further, according to researchers at Stanford University School of Medicine, a widely-available anti-inflammatory prescription drug can reduce the risk of a common skin cancer in humans. The scientists believe that although oral administration of celecoxib is associated with an increased risk of myocardial infarction and stroke in some people, it is possible that topical application could have a safer, protective effect for people prone to developing basal cell carcinomas (BCCs). The investigators dovetailed studies in mice with a randomised, double-blind, Phase II trial to reach their conclusions.
The researchers enrolled 60 people with a genetic predisposition to BCC in a three-year trial. Approximately half of the patients received celecoxib 200mg twice daily in a tablet format, while the others received a placebo. All patients were monitored at three-month intervals at one of four study sites for the development of new BCCs or the growth of previously-identified cancers. They found that, although both groups continued to develop new cancers during the study, oral celecoxib treatment decreased the growth of skin tumours by approximately 50 per cent, as compared to placebo, in participants who entered the trial with 15 or fewer BCCs. Celecoxib treatment also reduced the overall tumour burden in this group of patients.
Alice Rossiter
Editor, Cancer Drug News
Subscribe to:
Posts (Atom)