Phase II study of the insulin-like growth factor-1 receptor (IGF-1R) antibody cixutumumab (C) in patients (pts) with thymoma (T) and thymic carcinoma (TC).

Abstract

e17525 Background: Platinum-based chemotherapy is the standard of care for advanced unresectable T and TC. New options for treatment are needed for pts with recurrent or refractory disease. We have demonstrated expression of IGF-1R by immunohistochemistry (IHC) in 132 resected tumor specimen from pts with T and TC. C is an anti-IGF-1R monoclonal antibody that has shown activity in pts with thymic malignancies. Methods: Eligibility: Pts with recurrent T or TC who have received ≥ 1 prior platinum-containing regimen; measurable disease; PS 0-2; normal organ function. C is dosed at 20 mg/kg IV on day 1 of a 21-day cycle. Primary objective: to determine the objective response rate (PR+CR). Statistical design: Simon's optimal two stage design with two independent cohorts for T and TC. Toxicity is assessed every cycle using CTCAE version 3.0 and tumor response is assessed every 6 weeks using RECIST 1.0. Blood samples are being collected for pharmacokinetic (PK) and pharmacodynamic (PD) analysis. Results: From 8/2009 to 12/2009, 13 pts (7 males, 6 females; 5 T, 8 TC) enrolled. Median age: 54 yrs (26-72). Mean number of prior systemic regimens: 4.5 (1-11). A median of 3 cycles (1-7) of C has been administered so far. Treatment has been well tolerated. 2 pts developed grade (G) 4 asymptomatic hyperuricemia post treatment (attributed to C). Uric acid levels normalized spontaneously and no treatment was required. G3 toxicities included 1 case of asymptomatic AST elevation and 1 lymphopenia. 1 pt with pleural metastases adjacent to the chest wall developed G2 pain and erythema locally after treatment on 2 different occasions. Pain did not respond to opioids but significant benefit was noted with non-steroidal anti-inflammatory agent (NSAID) use. This pt has shown a reduction in measurable disease by 15%. 3 other pts developed post treatment pain: 1 G2 and 2 G1. 13 pts are evaluable for response. Best response so far is stable disease in 8 pts (4T and 4 TC). 5 pts had disease progression. PK and PD analysis is ongoing. Conclusions: Treatment with C is well tolerated. No objective responses have been observed so far. 4 pts have experienced tumor pain after therapy. The study is open to accrual to both cohorts. No significant financial relationships to disclose.