A pilot study of monoclonal antibody cG250 and low dose subcutaneous IL-2 in patients (pts) with advanced renal cell carcinoma (RCC)

Abstract

2558 Background: The median survival of pts with metastatic RCC is 10 months. No therapy has been shown to improve the survival of these pts. cG250 is a chimeric monoclonal antibody (MoAb) that recognizes the CAIX/MN antigen. cG250 induces Ab-dependent cellular cytotoxicity (ADCC) responses in vitro that can be enhanced by IL-2. Our previous trial using cG250 alone showed it is safe, that tumor-specific targeting is high and that the T½ of cG250 in the circulation is long. We studied the effects of adding daily low-dose subcutaneous (sc) IL-2 to cG250 for treatment of clear cell RCC. Methods: The endpoints of the trial were toxicity; immunological effects (human anti-chimeric antibodies [HACA], ADCC, natural killer [NK] and lymphokine-activated killer cell [LAK] activity); cG250 biodistribution and pharmacokinetics (PK); and antitumor effects. Eligible pts had unresectable metastastic or locally advanced clear cell RCC with measurable or evaluable disease. Nine pts were treated as follows. cG250: 10 mg/m2/week (wk) x 6wk (1st and 5th doses trace-labeled with 131I). IL-2: 1.25x106 IU/m2/day x 6wk. Results: Treatment was generally well tolerated with no adverse events attributable to cG250. Two pts required 50% dose reduction of IL-2 due to toxicity. No HACA was detected. Labeled cG250 showed excellent targeting of tumor deposits. cG250 PK: T½α 22.96±12.53 hrs, T½β 135.20±46.90. IL-2 did not affect cG250 PK. ADCC and/or LAK cell activity was enhanced in some pts. No antitumor responses were observed. Conclusions: Weekly cG250 with daily low-dose sc IL-2 is well tolerated. IL-2 does not influence the PK or biodistribution of cG250 and does not increase HACA. Some pts showed enhanced ADCC or LAK activity. Other strategies for enhancing the antitumor effect of cG250 are being explored. No significant financial relationships to disclose.