A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX®) and interferon-alpha-2a in metastatic renal cell carcinoma patients.

Purpose: To evaluate the efficacy and safety of WX-G250, a chimeric monoclonal antibody that binds to carboxy anhydrase IX, combined with low-dose interferon-alpha (LD-IFNα) in patients with progressive metastatic renal cell carcinoma (mRCC).

Patients And Methods: Thirty-one patients, nephrectomized for the primary tumor, clear cell progressive mRCC, were enrolled to receive weekly infusions of WX-G250 (20 mg i.v.; week 2-12) combined with LD-IFNα (3 MIU s.c. 3 times/week; week 1-12). At week 16, patients were evaluated for response and stratified into two groups: (a) responders into the extended treatment group for an additional 6 weeks of treatment or (b) the progressive group with no further study treatment.

Results: Of the 31 treated patients, 26 were evaluable for response to treatment. Two patients showed partial remission and 14 patients had stable disease as assessed in week 16. One patient experienced partial remission resulting in a complete remission lasting at least 17 months. Nine patients had durable stable disease of 24 weeks or longer. Clinical benefit was obtained in 42% (11/26) patients. The median overall survival achieved was 30 months and the 2-year survival was 57%. Patients receiving extended treatment showed a significantly longer 2-year survival rate than discontinued patients (79 vs. 30%; P=0.0083). In general, treatment was well tolerated with little toxicity.

Conclusion: Treatment with the antibody WX-G250 in combination with LD-IFNα is safe, well tolerated, led to clinically meaningful disease stabilization and demonstrated clinical benefit in this progressive mRCC patient population.