| General information |
| Database: | DB00150 |
| Objective: | Phase I expansion trial of an oral TORC1/TORC2 inhibitor (CC223) in advanced solid tumors |
| Authors: | Andrea Varga, et al |
| Title: | Phase I expansion trial of an oral TORC1/TORC2 inhibitor (CC223) in advanced solid tumors |
| Journal: | J Clin Oncol |
| Year: | 2013 ASCO Annual Meeting |
| PMID: | J Clin Oncol 31, 2013 (suppl; abstr 2606) |
| Trial Design |
| Clinical Trial Id: | NCT01177397 |
| Agent: | CC223
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I expansion trial |
| Key Patients Feature: | subjects with select advanced, refractory solid tumors |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Following establishment of the MTD (reported at ASCO 2012), subjects were enrolled in expansion cohorts of up to 20 evaluable subjects. CC223 was dosed at 45 mg once daily in 28 day cycles until disease progression. |
| Primary End Point: | MDT, DLT, PK, PD, PR, SD, Aes, PFS |
| Secondary End Point: | NA |
| Patients Number: | 101 |
| Trial Results |
| DLT_MTD: | CC223 dose reduction was required in > 50% of subjects with non small cell lung cancer and hepatocellular carcinoma, usually during cycle 1 or 2. Exposuredependent TORC1 (p4EBP1) and TORC2 (pAKT) inhibition was observed across cohorts. |
| Objective Response Rate: | mTOR pathway inhibition and/or decreased proliferation was demonstrated in paired tumor biopsies, but results were inconsistent. Reduction in glucose uptake (> 25% decrease in SUV) on PET imaging at day 15 was observed in 78% (14/18) of non small cell lung cancer and 69% (11/16) of hepatocellular carcinoma subjects. Partial tumor responses were observed in evaluable subjects with non small cell lung cancer (1/17; confirmed, treatment duration 36 weeks) and hepatocellular carcinoma (3/15; 1 confirmed, treatment duration 15 - 26 weeks). |
| Disease Control Rate: | Disease control rate in the overall non small cell lung cancer cohort was 42% (11/26) and in the hepatocellular carcinoma cohort |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | GBM subjects underwent salvage resections on study and none were progression free at 6 months. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common (> 20%) related adverse events (all grades) were fatigue, rash, stomatitis, hyperglycemia, anorexia, nausea, vomiting and diarrhea. In addition, related serious adverse events included infection (1), pneumonitis (4), renal insufficiency (2) and pancreatitis (2). |
| Conclusions: | Encouraging signals of biomarker and clinical activity were observed in hepatocellular carcinoma and non small cell lung cancer. Due to the frequency of dose reductions, select additional cohorts will be enrolled at a starting dose of 30 mg QD. |