Lani
10-24-2007, 10:43 AM
SF meeting of AACR paper on two new IGFR inhibitors (one a monoclonal antibody, one a Small molecule tyrosine kinase inhibitor)
ALthough only phase 1 these may be moved to Phase II for those looking for new upcoming drugs when running out of possibilities. The mAB is being tested in sarcomas, the TKI in other tumors including breast it seems
New IGF-1R Antagonist Shows Antitumor Activity in Sarcoma
October 24, 2007 — A new drug, one of the first in its class, has shown early evidence of promising activity against sarcoma. The product, R1507 (Roche), is a human monoclonal antibody that acts as an antagonist of the insulinlike growth factor receptor (IGF-1R). Details from a company-sponsored phase 1 clinical trial were reported yesterday at the International Conference on Molecular Targets and Cancer Therapeutics, in San Francisco, California.
The trial was conducted in 34 adult patients with advanced solid tumors, and R1507 was administered weekly by intravenous infusion. Lead investigator Stephen Leong, MD, from the University of Colorado Cancer Center, in Denver, told the meeting that antitumor effects had been observed in 11 of the 34 patients, with 2 patients showing a partial response (1 showed a 70% decrease in tumor size) and 9 showing stabilization of disease (no significant growth or progression for 6 weeks). The 2 patients with partial responses both had Ewing's sarcoma, as did 2 of the patients showing stabilization. A further 5 patients with stable disease had other sarcomas.
"For these patients to have control of their disease implies significant activity, but because the number of patients studied is so small, it is impossible to draw significant statistical conclusions," Dr. Leong told journalists at a press briefing during the meeting.
The drug appeared to be safe and well tolerated, Dr. Leong said; 9 patients reported adverse events, including 3 with fatigue and 2 with weight and appetite loss. None of the typical adverse effects of chemotherapy were seen. However, there were 2 serious adverse events that might have been related to the drug. One of these was the finding of elevated bilirubin levels; however, this patient had liver metastases, which might have been responsible for the finding, Dr. Leong said. The other was a stroke in a patient with a history of blood clots and hypertension.
The results from this phase 1 trial were encouraging enough for further trials to have already been started, Dr. Leong commented. A phase 2 study in adults with sarcoma and a phase 1 study in children are currently in progress.
Oral Drug Acting on Same Target
Another drug that also targets IGF-1R, but this time a small molecule that can be taken orally, was described at the meeting. OSI-906, under development at OSI Pharmaceuticals, has just started phase 1 clinical trials in patients with advanced solid tumors.
IGF-1R is expressed on the surface of many human cancer cells and is known to be a driver of tumor growth. In preclinical studies described at the meeting by company researcher Jonathan Pachter, PhD, OSI-906 reduced tumor growth in 15 of 28 cells lines, including those representative of colorectal, lung, breast, pancreatic, and pediatric tumors. It was particularly effective against colorectal cancers (which are highly IGF-1R–dependent).
The drug also showed synergy with the epidermal growth factor inhibitor erlotinib (Tarceva, Genentech) in mice with human colorectal cancer tumors. Oral administration of OSI-906 or erlotinib alone significantly reduced further growth of the tumors, Dr. Pachter noted. But when the 2 drugs were combined, tumor growth was fully halted and the tumors decreased by 22%, he said.
International Conference on Molecular Targets and Cancer Therapeutics: Abstracts A78 and C192. Presented October 23, 2007.
ALthough only phase 1 these may be moved to Phase II for those looking for new upcoming drugs when running out of possibilities. The mAB is being tested in sarcomas, the TKI in other tumors including breast it seems
New IGF-1R Antagonist Shows Antitumor Activity in Sarcoma
October 24, 2007 — A new drug, one of the first in its class, has shown early evidence of promising activity against sarcoma. The product, R1507 (Roche), is a human monoclonal antibody that acts as an antagonist of the insulinlike growth factor receptor (IGF-1R). Details from a company-sponsored phase 1 clinical trial were reported yesterday at the International Conference on Molecular Targets and Cancer Therapeutics, in San Francisco, California.
The trial was conducted in 34 adult patients with advanced solid tumors, and R1507 was administered weekly by intravenous infusion. Lead investigator Stephen Leong, MD, from the University of Colorado Cancer Center, in Denver, told the meeting that antitumor effects had been observed in 11 of the 34 patients, with 2 patients showing a partial response (1 showed a 70% decrease in tumor size) and 9 showing stabilization of disease (no significant growth or progression for 6 weeks). The 2 patients with partial responses both had Ewing's sarcoma, as did 2 of the patients showing stabilization. A further 5 patients with stable disease had other sarcomas.
"For these patients to have control of their disease implies significant activity, but because the number of patients studied is so small, it is impossible to draw significant statistical conclusions," Dr. Leong told journalists at a press briefing during the meeting.
The drug appeared to be safe and well tolerated, Dr. Leong said; 9 patients reported adverse events, including 3 with fatigue and 2 with weight and appetite loss. None of the typical adverse effects of chemotherapy were seen. However, there were 2 serious adverse events that might have been related to the drug. One of these was the finding of elevated bilirubin levels; however, this patient had liver metastases, which might have been responsible for the finding, Dr. Leong said. The other was a stroke in a patient with a history of blood clots and hypertension.
The results from this phase 1 trial were encouraging enough for further trials to have already been started, Dr. Leong commented. A phase 2 study in adults with sarcoma and a phase 1 study in children are currently in progress.
Oral Drug Acting on Same Target
Another drug that also targets IGF-1R, but this time a small molecule that can be taken orally, was described at the meeting. OSI-906, under development at OSI Pharmaceuticals, has just started phase 1 clinical trials in patients with advanced solid tumors.
IGF-1R is expressed on the surface of many human cancer cells and is known to be a driver of tumor growth. In preclinical studies described at the meeting by company researcher Jonathan Pachter, PhD, OSI-906 reduced tumor growth in 15 of 28 cells lines, including those representative of colorectal, lung, breast, pancreatic, and pediatric tumors. It was particularly effective against colorectal cancers (which are highly IGF-1R–dependent).
The drug also showed synergy with the epidermal growth factor inhibitor erlotinib (Tarceva, Genentech) in mice with human colorectal cancer tumors. Oral administration of OSI-906 or erlotinib alone significantly reduced further growth of the tumors, Dr. Pachter noted. But when the 2 drugs were combined, tumor growth was fully halted and the tumors decreased by 22%, he said.
International Conference on Molecular Targets and Cancer Therapeutics: Abstracts A78 and C192. Presented October 23, 2007.