TY - JOUR
T1 - Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer
AU - Borghaei, Hossein
AU - Alpaugh, Katherine
AU - Hedlund, Gunnar
AU - Forsberg, Göran
AU - Langer, Corey
AU - Rogatko, Andre
AU - Hawkins, Robert
AU - Dueland, Svein
AU - Lassen, Ulrik
AU - Cohen, Roger B
PY - 2009/9/1
Y1 - 2009/9/1
N2 - PURPOSE: Two phase I studies were conducted of ABR-217620 alone or in combination with docetaxel. This is a recombinant fusion protein consisting of a mutated variant of the superantigen staphylococcal enterotoxin E (SEA/E-120) linked to fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4.PATIENTS AND METHODS: Patients with non-small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose escalation monotherapy [MONO] study). Doses were selected based on individual patient anti-SEA/E-120 titers pretreatment. Patients with NSCLC received 4 daily, escalating doses of ABR-217620 followed by docetaxel in 21-day cycles (ABR-217620 dose escalation combination with docetaxel [COMBO] study).RESULTS: Thirty-nine patients were enrolled in the MONO study and 13 were enrolled in the COMBO study. The monotherapy MTD was 26 microg/kg (NSCLC and PC) and 15 microg/kg (RCC). Dose-limiting toxicities (DLTs) in the MONO study were fever, hypotension, acute liver toxicity, and vascular leak syndrome. In the COMBO study, the MTD was 22 microg/kg (neutropenic sepsis). Adverse events included grade 1 to 2 fever, hypotension, nausea, and chills. Treatment caused a systemic increase of inflammatory cytokines and selective expansion of SEA/E-120 reactive T-cells. Tumor biopsies demonstrated T-cell infiltration after therapy. Fourteen patients (36%) had stable disease (SD) on day 56 of the MONO study. Two patients (15%) in the COMBO study had partial responses, one in a patient with progressive disease on prior docetaxel, and five patients (38%) had SD on day 56.CONCLUSION: ABR-217620 was well tolerated with evidence of immunological activity and antitumor activity.
AB - PURPOSE: Two phase I studies were conducted of ABR-217620 alone or in combination with docetaxel. This is a recombinant fusion protein consisting of a mutated variant of the superantigen staphylococcal enterotoxin E (SEA/E-120) linked to fragment antigen binding moiety of a monoclonal antibody recognizing the tumor-associated antigen 5T4.PATIENTS AND METHODS: Patients with non-small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose escalation monotherapy [MONO] study). Doses were selected based on individual patient anti-SEA/E-120 titers pretreatment. Patients with NSCLC received 4 daily, escalating doses of ABR-217620 followed by docetaxel in 21-day cycles (ABR-217620 dose escalation combination with docetaxel [COMBO] study).RESULTS: Thirty-nine patients were enrolled in the MONO study and 13 were enrolled in the COMBO study. The monotherapy MTD was 26 microg/kg (NSCLC and PC) and 15 microg/kg (RCC). Dose-limiting toxicities (DLTs) in the MONO study were fever, hypotension, acute liver toxicity, and vascular leak syndrome. In the COMBO study, the MTD was 22 microg/kg (neutropenic sepsis). Adverse events included grade 1 to 2 fever, hypotension, nausea, and chills. Treatment caused a systemic increase of inflammatory cytokines and selective expansion of SEA/E-120 reactive T-cells. Tumor biopsies demonstrated T-cell infiltration after therapy. Fourteen patients (36%) had stable disease (SD) on day 56 of the MONO study. Two patients (15%) in the COMBO study had partial responses, one in a patient with progressive disease on prior docetaxel, and five patients (38%) had SD on day 56.CONCLUSION: ABR-217620 was well tolerated with evidence of immunological activity and antitumor activity.
KW - Adult
KW - Aged
KW - Antibodies, Monoclonal/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Carcinoma, Non-Small-Cell Lung/drug therapy
KW - Cytokines/blood
KW - Docetaxel
KW - Enterotoxins/administration & dosage
KW - Europe
KW - Female
KW - Humans
KW - Immunoconjugates
KW - Kidney Neoplasms/drug therapy
KW - Lung Neoplasms/drug therapy
KW - Lymphocyte Activation/drug effects
KW - Lymphocytes, Tumor-Infiltrating/drug effects
KW - Male
KW - Middle Aged
KW - Pancreatic Neoplasms/drug therapy
KW - Recombinant Fusion Proteins/administration & dosage
KW - Taxoids/administration & dosage
KW - Time Factors
KW - Treatment Outcome
KW - United States
U2 - 10.1200/JCO.2008.20.2515
DO - 10.1200/JCO.2008.20.2515
M3 - Journal article
C2 - 19636016
SN - 0732-183X
VL - 27
SP - 4116
EP - 4123
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 25
ER -