1115PD - A phase 2 randomized study of ramucirumab (IMC 1121B; RAM) with or without dacarbazine (DTIC) in patients (pts) with metastatic melanoma (MM) (CP12-...

Date 29 September 2012
Event ESMO Congress 2012
Session Melanoma
Topics Anticancer agents
Skin cancers
Melanoma
Therapy
Biological therapy
Presenter Richard Carvajal
Authors R. Carvajal1, J. Thompson2, M.S. Gordon3, K. Lewis4, A. Pavlick5, J.D. Wolchok6, P. Rojas7, J. Schwartz8, A. Bedikian9
  • 1Memorial Sloan-Kettering Cancer Center, New York/US
  • 2Medical L Oncology, Seattle Cancer Care Alliance, Seattle/US
  • 3Pinnacle Oncology Hematology, Oncology Research Associates, Scottsdale/US
  • 4Medical Oncology, University of Colorado Denver, Aurora/US
  • 5Hematology-oncology, New York University, New York/US
  • 6/
  • 7Biostatistics, ImClone Systems, 08807 - Bridgewater/US
  • 8Medical, ImClone Systems, 08807 - Bridgewater/US
  • 9Melanoma Medical Oncology, MD Anderson Cancer Center, Houston/US

Abstract

Background

Vascular endothelial growth factor (VEGF)-mediated angiogenesis contributes to MM pathogenesis. RAM is a fully human IgG1 recombinant monoclonal antibody that inhibits VEGF receptor-2 (VEGFR-2) ligand binding and signaling. We investigated RAM alone and in combination with DTIC in chemotherapy-naïve MM pts.

Methods

Eligible pts had stage IV cutaneous MM, ECOG PS 0-1, adequate hematologic, hepatic, and renal function. Therapy (Rx) in Arm A: RAM (10 mg/kg) + DTIC (1000 mg/m2); Arm B: RAM (10 mg/kg). Rx was every (q) 3 weeks (wk); tumor assessments were q6 wk. The primary endpoint was progression-free survival (PFS); other endpoints were safety, response, overall survival (OS).

Results

106 pts were randomized; 102 received study Rx. Arm A (n = 52) median (medn) age was 63, 71% male, 37% had elevated LDH, 23% stage M1c. Arm B (n = 50) medn age was 62, 76% male, 38% had elevated LDH, 36% stage M1c. Medn PFS was 2.6 months (m) Arm A and 1.7m Arm B; 6m PFS rates were 31% and 18%; 12m PFS rates were 24% and 16% on Arms A and B, respectively. There were 9 (17%) partial responses (PR) & 19 (37%) with stable disease (SD); 2 (4%) PR & 21(42%) SD on Arms A and B, respectively. Medn OS was 8.7m Arm A; 11m Arm B. Nonhematologic adverse events (AEs) considered at least possibly related to RAM included fatigue (50%; 4% Grade [G] ≥3), hypertension ([HTN] 21%; 15% G ≥3), infusion-related reactions ([IRR] 8%; 0 G ≥3), proteinuria ([PU] 8%; 4% G ≥ 3), headache ([HA] 10%; 2% G ≥3) on Arm A; fatigue (30%; 2% G ≥3), HTN (22%; 14% G ≥3), IRR (14%; 6% G ≥3), PU (12%; 2% G ≥3), HA (20%; 0 G ≥3) on Arm B. IRR incidence was reduced following a recommendation for premedication after 37 pts received initial Rx. Hematologic AEs were neutropenia ([NP] 33%; 19% G ≥3), thrombocytopenia ([TP] 39%; 15% G ≥3), and anaemia ([A]14%; 4% G ≥3) on Arm A; NP (0%), TP (6%; 0 G ≥3) and A (2%; 0 G ≥3) on Arm B.

Conclusions

RAM alone or in combination with DTIC was associated with acceptable incidence of AEs in MM. Clinical activity was modest on both arms. Although the study was not powered for definitive comparison between treatment arms, PFS appeared greater in Arm A. Biomarker analysis is ongoing.

Disclosure

R. Carvajal: Cosulting, Novartis - money paid to me Consulting, Morphotek - money paid to me Grants, NIH/NCI - money paid to me Grants, FDA - money paid to me Grants, ASCO - money paid to me.

J. Thompson: ImClone provided funding to the University of Washington to support this research.

K. Lewis: Research Funding - ImClone.

J. Wolchok: Consultant - Bristol Myers Squibb; Merck; GlaxoSmithKline Research support - Bristol Myers Squibb and GlaxoSmithKline.

P. Rojas: I am an employee of Lilly and own Lilly stock.

J. Schwartz: I am an employee of Lilly and own Lilly stock.

All other authors have declared no conflicts of interest.