Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206 - PubMed (original) (raw)
Clinical Trial
. 2005 Dec 10;23(35):8968-77.
doi: 10.1200/JCO.2005.01.109. Epub 2005 Oct 3.
Luis H Camacho, Gabriel Lopez-Berestein, Dmitri Pavlov, Cecile A Bulanhagui, Robert Millham, Begoña Comin-Anduix, James M Reuben, Elisabeth Seja, Charla A Parker, Amarnath Sharma, John A Glaspy, Jesus Gomez-Navarro
Affiliations
- PMID: 16204013
- DOI: 10.1200/JCO.2005.01.109
Clinical Trial
Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206
Antoni Ribas et al. J Clin Oncol. 2005.
Abstract
Purpose: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with CP-675,206, a fully human anti-CTLA4 monoclonal antibody, may break peripheral immunologic tolerance leading to effective immune responses to cancer in humans. A phase I trial was conducted to test the safety of CP-675,206.
Patients and methods: Thirty-nine patients with solid malignancies (melanoma, n = 34; renal cell, n = 4; colon, n = 1) received an intravenous (IV) infusion of CP-675,206 at seven dose levels. The primary objective was to determine the maximum-tolerated dose and the recommended phase II dose.
Results: Dose-limiting toxicities and autoimmune phenomena included diarrhea, dermatitis, vitiligo, panhypopituitarism and hyperthyroidism. Two patients experienced complete responses (maintained for 34+ and 25+ months), and there were two partial responses (26+ and 25+ months) among 29 patients with measurable melanoma. There have been no relapses thus far after objective response to therapy. Four other patients had stable disease at end of study evaluation (16, 7, 7, and 4 months). Additionally, five patients had extended periods without disease progression (36+, 35+, 26+, 24+, and 23+ months) after local treatment of progressive metastases. Longer systemic exposure to CP-675,206 achieved in higher dose cohorts predicted for a higher probability of response.
Conclusion: CP-675,206 can be administered safely to humans as a single IV dose up to 15 mg/kg, resulting in breaking of peripheral immune tolerance to self-tissues and antitumor activity in melanoma.
Comment in
- CTLA-4 blockade: autoimmunity as treatment.
Kapadia D, Fong L. Kapadia D, et al. J Clin Oncol. 2005 Dec 10;23(35):8926-8. doi: 10.1200/JCO.2005.07.012. Epub 2005 Oct 3. J Clin Oncol. 2005. PMID: 16204008 No abstract available.
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