Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer
| Autor: | Jordan Berlin, Steven J. Cohen, David M. Goldenberg, Richard M Goldberg, John L. Marshall, Pamela S. Simpson, Alexander Starodub, Christopher H. Lieu, Michael J. Guarino, Robert M. Sharkey, Serengulam V. Govindan, William A. Wegener, Wells A. Messersmith, J. Randolph Hecht, Efrat Dotan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cancer Research Colorectal cancer Drug Resistance Gastroenterology 0302 clinical medicine Carcinoembryonic antigen Monoclonal 80 and over Medicine Neoplasm Metastasis Infusions Intravenous Humanized 6.2 Cellular and gene therapies Cancer Aged 80 and over Leukopenia biology ORIGINAL REPORTS Middle Aged Colo-Rectal Cancer Treatment Outcome Oncology 5.1 Pharmaceuticals Response Evaluation Criteria in Solid Tumors 6.1 Pharmaceuticals 030220 oncology & carcinogenesis Disease Progression Female Development of treatments and therapeutic interventions medicine.symptom Intravenous Colorectal Neoplasms medicine.drug Half-Life Adult Infusions medicine.medical_specialty Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Antineoplastic Agents Neutropenia Antibodies Monoclonal Humanized Irinotecan Antibodies Disease-Free Survival Drug Administration Schedule 03 medical and health sciences Clinical Research Internal medicine Humans Oncology & Carcinogenesis Survival analysis Aged business.industry Evaluation of treatments and therapeutic interventions medicine.disease Survival Analysis Surgery Clinical trial 030104 developmental biology Drug Resistance Neoplasm biology.protein Neoplasm Camptothecin Digestive Diseases business |
| Zdroj: | J Clin Oncol Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 35, iss 29 |
| Popis: | Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles. End points were safety, response, pharmacokinetics, and immunogenicity. Results Eighty-six patients who had undergone a median of five prior therapies (range, one to 13) were each enrolled into one of the four cohorts. On the basis of Response Evaluation Criteria in Solid Tumors 1.1, 38% of these patients had a tumor as well as plasma carcinoembryonic antigen reduction from baseline after labetuzumab govitecan treatment; one patient achieved a partial response with a sustained response spanning > 2 years, whereas 42 patients had stable disease as the best overall response. Median progression-free survival and overall survival were 3.6 and 6.9 months, respectively. The major toxicities (grade ≥ 3) among all cohorts were neutropenia (16%), leukopenia (11%), anemia (9%), and diarrhea (7%). The antibody-drug conjugate’s mean half-life was 16.5 hours for the four cohorts. Anti-drug/anti-antibody antibodies were not detected. The two once-weekly dose schedules, showing comparable toxicity and efficacy, were chosen for further study. Conclusion Monotherapy with labetuzumab govitecan demonstrated a manageable safety profile and therapeutic activity in heavily pretreated patients with metastatic colorectal cancer, all with prior irinotecan therapy. Further studies of labetuzumab govitecan treatment alone or in combination with other therapies in earlier settings are indicated. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|