Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease.
This trial assessed the safety and efficacy of LM in combination with carboplatin/etoposide therapy compared to carboplatin/etoposide treatment alone in patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC).



A run-in phase 1 stage was used to determine the recommended phase 2 dose and characterize the dose-limiting toxicities of LM in combination with carboplatin/etoposide followed by LM alone in patients with CD56-positive solid tumors. In phase 2, chemotherapy-naive ED-SCLC patients were randomized 2:1 to carboplatin AUC (area under the plasma concentration vs. time curve) of 5 day 1 + etoposide 100 mg/m2days 1 to 3 plus LM (arm 1) or alone (arm 2).



In the phase 1 study (n = 33), a dose of LM at 112 mg/m2with carboplatin/etoposide was identified as the recommended phase 2 dose. However, because of an increased incidence of peripheral neuropathy events during early phase 2, this dose was reduced to 90 mg/m2. In phase 2, a total of 94 and 47 evaluable patients were assigned to arms 1 and 2, respectively. No difference in median progression-free survival was observed between arms 1 and 2 (6.2 vs. 6.7 months). The most common treatment-emergent adverse event leading to discontinuation was peripheral neuropathy (29%). A total of 21 patients had a treatment-emergent adverse event leading to death (18 in arm 1 and 3 in arm 2); for 10 individuals, this was an infection (pneumonia or sepsis) deemed to be related to the study drug.



The combination of LM plus carboplatin/etoposide did not improve efficacy over standard carboplatin/etoposide doublet therapy in ED-SCLC patients and showed increased toxicity, including a higher incidence of serious infections with fatal outcomes.
Division of Hematology/Oncology, Univeristy of Pittsburgh Cancer Institute, Pittsburgh, PA. Electronic address: socinskima@upmc.edu.
Mark A
MA
Socinski
Hematology-Oncology, University of Florida College of Medicine, Gainesville, FL.
Frederic J
FJ
Kaye
Lung Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN.
David R
DR
Spigel
Cancer Center, South Carolina Oncology Associates, Columbia, SC.
Fred J
FJ
Kudrik
Medical Oncology Department, Hospital Universitario 12 de Octubre and Lung Cancer Unit CNIO, Madrid, Spain.
Santiago
S
Ponce
Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
Peter M
PM
Ellis
Servei d'Oncologia Mèdica, Hospital Sant Pau, Barcelona, Spain.
Margarita
M
Majem
Division of Molecular and Clinical Cancer Sciences, University of Manchester/Christie NHS Foundation Trust, Manchester, UK.
Paul
P
Lorigan
Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA.
Leena
L
Gandhi
Bienes Cancer Center, Holy Cross Hospital, Fort Lauderdale, FL.
Martin E
ME
Gutierrez
Clinical Development, ImmunoGen Inc, Waltham, MA.
Dale
D
Nepert
Medical Oncology Department, Hospital Universitario 12 de Octubre and Lung Cancer Unit CNIO, Madrid, Spain.
Jesus
J
Corral
Medical Oncology Department, Hospital Universitario 12 de Octubre and Lung Cancer Unit CNIO, Madrid, Spain.
Luis Paz
LP
Ares
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019002:CD56 Antigen / Q000737:chemistry* / Q000276:immunology; D016190:Carboplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D019002:CD56 Antigen; D018796:Immunoconjugates; C522918:NCAM1 protein, human; C579429:lorvotuzumab mertansine; D008453:Maytansine; D005047:Etoposide; D016190:Carboplatin
Clinical trial; Combination therapy; SCLC; Targeted drug delivery; Tolerability