1543TiP - Phase I/II study to assess the safety, pharmacokinetics (PK) and efficacy of lorvotuzumab mertansine (LM, IMGN901) in combination with carboplatin/e...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Clinical Research
Small Cell Lung Cancer
Basic Scientific Principles
Presenter David Spigel
Authors D.R. Spigel1, J. Bendell2, A. Mita3, A. Argiris3, C. Kurkjian4, C.L. Hann5, Z. Segota6, R. Guild7, R. Mastico7, M.E. Guiterrez6
  • 1Sarah Cannon Research Institute, 37203 - Nashville/US
  • 2Drug Development Unit, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 3Oncology, University of Texas Health Sciences Center, San Antonio/US
  • 4Cancer Center, The Univesity of Oklahoma Cancer Inst., 73104 - Oklahoma City/US
  • 5Cancer Center, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 21231 - Baltimore/US
  • 6Cancer Center, Holy Cross Hospital, 33308 - Fort Lauderdale/US
  • 7Pharmacokinetics Lab, ImmunoGen, Inc., 02451 - Waltham/US

Abstract

Purpose

SCLC expresses CD56 almost universally. LM is a CD56-targeting antibody-drug conjugate. This study was initiated to evaluate LM for the treatment of SCLC when used in combination with carboplatin (C) and etoposide (E). Its phase 1 portion was designed to establish the recommended phase 2 dose (RP2D) of LM with C and E. PK data with the combination also was obtained.

Methods

Patients (pts) with advanced solid tumors were accrued to a standard 3 + 3 dose-escalation study design. Successive cohorts received escalating doses of LM IV on days 1 and 8 in combination with C IV on day 1 and E IV on days 1-3 every 21 days. LM PK was measured by an ELISA-based method. C and E levels were measured using optimized LC-MS/MS assays. PK parameters were determined by noncompartmental analysis.

Results

33 patients (13M, median age = 57.3) were treated in 5 cohorts (2 using C AUC6; 3 using C AUC5) at LM doses ranging from 60-112 mg/m2. The RP2D was defined as LM 112 mg/m2 with C AUC5 and E 100 mg/m2. PK samples were analyzed for Cycle 1, first dose. At the RP2D, LM exposure and maximum concentration were similar to those observed in single-agent trials, with the t1/2 of LM approaching 1 day (24.2 hours). PK findings for C/E were similar to published reports (Oguri, 1988; D'Incalci, 1982) with the observed AUC of C = 5.1 ± 0.7 min*mg/mL and E = 6921 ± 1231 min*µg/mL. The most common treatment-related adverse events (AEs) were anemia, thrombocytopenia, nausea, peripheral neuropathy, decreased lymphocytes and neutrophils, and fatigue. The majority of related grade 3/4 AEs were cytopenias which, while known to occur with C/E regimens, typically have not been associated with LM monotherapy. Among 13 pts with SCLC accrued to phase 1, 6 (46%; 4 previously treated) achieved PR after at least one response assessment.

Conclusion

The combination is well tolerated with no apparent drug-drug interactions. Preliminary signs of activity have been observed in this predominantly pre-treated population. The randomized phase 2 portion of the study in chemo-naïve patients with SCLC has opened to accrual. Updated data will be presented.

Disclosure

R. Guild: Employee of ImmunoGen, Inc.

R. Mastico: Employee of ImmunoGen, Inc.

All other authors have declared no conflicts of interest.