Entry Detail
| General information | |
| Database: | DB00162 |
| Objective: | Bcl2 is a critical regulator of apoptosis that is overexpressed in the majority of small cell lung cancers (SCLC). Nativoclax (ABT263) is a potent and selective inhibitor of Bcl2 and Bclx(L). The primary objectives of thisphase IIa study included safety at the recommendedphase II dose and preliminary, exploratory efficacy assessment in patients with recurrent and progressive SCLC after at least one prior therapy. |
| Authors: | Rudin CM, et al |
| Title: | Phase II study of singleagent navitoclax (ABT263) and biomarker correlates in patients with relapsed small cell lung cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22496272 |
| Trial Design | |
| Clinical Trial Id: | NCT00445198 |
| Agent: | navitoclax |
| Target: | Bcl2like protein 2 Antiapoptotic protein BCLXL Apoptosis regulator Bcl2 |
| Cancer Type: | smallcell lung cancer |
| Cancer Subtype: | relapsed small cell lung cancer. |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | the phase II component of this clinical trial was an openlabel, singlearm study of patients with recurrent and progressive SCLC after at least one prior therapy. |
| Key Patients Feature: | patients with recurrent and progressive SCLC after at least one prior therapy. |
| Biomarker: | Exploratory analyses revealed baseline levels of cytokeratin 19 fragment antigen 211, neuronspecific enolase, proGRP, and circulating tumor cell number as correlates of clinical benefit. |
| Biomark Analysis: | Exploratory analyses revealed baseline levels of cytokeratin 19 fragment antigen 211, neuronspecific enolase, proGRP, and circulating tumor cell number as correlates of clinical benefit. |
| Control Group Info: | single arm |
| Treatment Info: | patients received navitoclax 325 mg daily, following an initial leadin of 150 mg daily for 7 days. |
| Primary End Point: | safety at the recommended phase 2 dose and preliminary, exploratory efficacy assessment. |
| Secondary End Point: | safety and toxicity assessment, response rate, progression free and overall survival (PFS and OS), as well as exploratory pharmacodynamic correlates. |
| Patients Number: | 39 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | Partial response was observed in one (2.6%) patient and stable disease in 9 (23%) patients. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 1.5 months |
| Median OS A vs. C: | median OS was 3.2 months. |
| Adverse Event(agent arm): | The most common toxicity associated with navitoclax was thrombocytopenia, which reached grade IIIIV in 41% of patients. |
| Conclusions: | Bcl2 targeting by navitoclax shows limited singleagent activity against advanced and recurrent SCLC. Correlative analyses suggest several putative biomarkers of clinical benefit. Preclinical models support that navitoclax may enhance sensitivity of SCLC and other solid tumors to standard cytotoxics. Future studies will focus on combination therapies. |