Canbas Co., Ltd.: CBP501 Met Primary Endpoint of Phase II Study in Malignant Pleural Mesothelioma
Published: Jun 04, 2012
This is a randomized phase 2 trial for chemotherapy naïve patients with unresectable MPM, comparing the experimental arm (pemetrexed, cisplatin and CBP501 (25mg/m2)) and the control arm (pemetrexed and cisplatin alone). 65 patients were randomized 2:1 to the experimental arm and the control arm. The patients in both arms were injected intravenously on day 1 of a 21-day treatment cycle and continued on treatment until disease progression or intolerable toxicities developed.
The primary endpoint of progression free survival (PFS) rate at 4 months in the experimental arm was 68% (27/40) and met the predefined criteria (>55%(23/42)), which represents a positive anti-tumor activity worthwhile to conduct the subsequent phase III trial.
In addition, the experimental arm consistently showed a trend toward better efficacy across the efficacy endpoints of objective response rate, progression free survival and overall survival, although this study is relatively small study without a sample size sufficient to test a statistically significant difference between the two arms for each endpoint.
Any grade 3-4 treatment-related toxicities specific to the experimental arm were not observed. 70% of patients treated with CBP501 had infusion reactions, all grade 1-2.
Dr. L. M. Krug (Memorial Sloan-Kettering Cancer Center), the principle investigator of this trial, and the other investigators concluded as follows:
"This study met its primary endpoint. And response rate and progression free survival also favored the triplet combination arm. No added toxicities were noted with the addition of CBP501 aside from the infusion reactions which were all grade 1-2. These preliminary data suggest that a phase III trial may be warranted."
The followings are the preliminary results analyzed by the company, which includes the data that has not been presented at the ASCO meeting.
The experimental arm showed a statistically significant 49% reduction in the risk of the patients’ disease worsening or death. The median PFS (modified RECIST), assessed by investigators, improved by 1.7 months from 4.7 months in the control arm to 6.4 months in the experimental arm (HR=0.506, p=0.03).
Although we could not secure sufficient follow-up period in this study, the experimental arm showed a trend toward improved overall survival (OS), compared with the control arm. In the per-protocol population (three patients with significant protocol violations and an early withdrawal in the treated population were excluded), the median OS improved by 3.8 months from 11.2 months in the control arm to 15.0 months in the experimental arm (p>0.05).
"I am very satisfied with and encouraged by the preliminary results of phase II study, achieving the primary endpoint, " said Dr. Takumi Kawabe, CEO of CanBas, "Based on this positive results, we are confident to further develop CBP501, forming a partnership with a pharmaceutical company. We will devote every effort to achieve our corporate mission - develop and deliver good anticancer medicines to patients as soon as possible. "
Malignant mesothelioma is a cancer of the mesothelium (the sac that lines internal body cavities) with a poor prognosis. Pleural mesothelioma (MPM) comprises the majority of all cases; the main risk factor is a continuous exposure to asbestos. The US incidence of MPM is approximately 2,500. Because malignant mesothelioma is extremely aggressive and has a long latency period (20 to 50years), cases are not usually detected until the disease has reached advanced stages. For most patients, systemic chemotherapy is the only treatment option.
CanBas’ lead product, CBP501 is a novel synthetic peptide which was discovered using CanBas’ proprietary phenotypic screen for G2 abrogation activity. CBP501 acts to increases sensitivity of cancer cells to cisplatin but not affect normal cells by multiple pathways, which include G2 checkpoint abrogation which suppress DNA damage repair and modulation of calmodulin activity which leads to increased accumulation of platinum in tumor cells.
CanBas is currently conducting randomized Phase II clinical trials in the US and other countries using CBP501 in combination therapy for first-line treatment of patients with non-small cell lung cancer (NSCLC); the study achieved full enrollment in October 2011. Phase I studies have demonstrated promising combination efficacy in platinum resistant ovarian cancer.
CanBas is a publicly listed (Tokyo Stock Exchange: M-4575) clinical-stage biopharmaceutical company focused on the discovery and development of novel oncology drugs targeting the cell cycle. Using its proprietary phenotypic screening platform, CanBas has identified a pipeline of novel oncology drug candidates, including its lead product, CBP501. CanBas’ pipeline also includes CBS9106, a preclinical stage, synthetic small molecule that demonstrates cancer cell-specific cytotoxicity, both alone and in synergy with specific DNA-damaging treatments, acting through inhibition and destabilization of CRM1.
Source: CanBas Co., Ltd.
Takumi Kawabe, CEO
CanBas Co., Ltd.