A phase 2 randomised study of ramucirumab (IMC-1121B) with or without dacarbazine in patients with metastatic melanoma

Abstract

Background: To evaluate the efficacy and safety of ramucirumab (IMC-1121B; LY3009806), a fully human monoclonal antibody targeting the vascular endothelial growth factor receptor-2, alone and in combination with dacarbazine in chemotherapy-naïve patients with metastatic melanoma (MM).

Methods: Eligible patients received ramucirumab (10mg/kg) + dacarbazine (1000 mg/m(2)) (Arm A) or ramucirumab only (10mg/kg) (Arm B) every 3 weeks. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), overall response and safety.

Findings: Of 106 randomised patients, 102 received study treatment (Arm A, N=52; Arm B, N=50). Baseline characteristics were similar in both arms. Median PFS was 2.6 months (Arm A) and 1.7 months (Arm B); median 6-month PFS rates were 30.7% and 17.9% and 12-month PFS rates were 23.7% and 15.6%, respectively. In Arm A, 9 (17.3%) patients had partial response (PR) and 19 (36.5%), stable disease (SD); PR and SD in Arm B were 2 (4.0%) and 21 (42.0%), respectively. Median OS was 8.7 months in Arm A and 11.1 months in Arm B. Patients in both arms tolerated the treatment with limited Grade 3/4 toxicities.

Interpretation: Ramucirumab alone or in combination with dacarbazine was associated with an acceptable safety profile in patients with MM. Although the study was not powered for comparison between treatment arms, PFS appeared greater with combination therapy. Sustained disease control was observed on both study arm.

Trial registration: ClinicalTrials.gov NCT00533702.

Keywords: Metastatic melanoma; Phase II; Ramucirumab.

Figure 1

a. Kaplan-Meier plot for progression-free survival by treatment arm of mITT population. b. Exploratory analyses of the effect of an adverse event (AE) of hypertension of progression-free survival (PFS), (mITT population). Kaplan-Meier plot for PFS of patients with or without an AE of hypertension (n=12 in Arm A; n=13 in Arm B). In both treatment arms, the median PFS appeared longer in patients with an AE of hypertension (6·8 months [95% CI: 1·3–16·4] for RAM + DTIC; 3·4 months [95% CI: 1·4–12·5] for RAM) than that in patients without an AE of hypertension (2·0 months [95% CI: 1·4–4·1] for RAM + DTIC; 1·5 months [95% CI: 1·4–2·7] for RAM).

Figure 1

a. Kaplan-Meier plot for progression-free survival by treatment arm of mITT population. b. Exploratory analyses of the effect of an adverse event (AE) of hypertension of progression-free survival (PFS), (mITT population). Kaplan-Meier plot for PFS of patients with or without an AE of hypertension (n=12 in Arm A; n=13 in Arm B). In both treatment arms, the median PFS appeared longer in patients with an AE of hypertension (6·8 months [95% CI: 1·3–16·4] for RAM + DTIC; 3·4 months [95% CI: 1·4–12·5] for RAM) than that in patients without an AE of hypertension (2·0 months [95% CI: 1·4–4·1] for RAM + DTIC; 1·5 months [95% CI: 1·4–2·7] for RAM).

Figure 2

a. Kaplan-Meier plot for overall survival by treatment arm of mITT population. b. Exploratory analyses of the effect of an AE of hypertension of overall survival (OS), (mITT population). Kaplan-Meier plot for OS of patients with or without an AE of hypertension (n=12 in Arm A; n=13 in Arm B). In both treatment arms, the median OS appeared longer in patients with an AE of hypertension (15·3 months, [95% CI: 5·4–‘not applicable’] for RAM + DTIC; 13·5 months [95% CI: 5·1–31·7] for RAM) than that in patients without (7·9 months [95% CI 6·3–12·9] for RAM + DTIC; 11·1 months [95% CI 7·0–13·2] for RAM).

Figure 2

a. Kaplan-Meier plot for overall survival by treatment arm of mITT population. b. Exploratory analyses of the effect of an AE of hypertension of overall survival (OS), (mITT population). Kaplan-Meier plot for OS of patients with or without an AE of hypertension (n=12 in Arm A; n=13 in Arm B). In both treatment arms, the median OS appeared longer in patients with an AE of hypertension (15·3 months, [95% CI: 5·4–‘not applicable’] for RAM + DTIC; 13·5 months [95% CI: 5·1–31·7] for RAM) than that in patients without (7·9 months [95% CI 6·3–12·9] for RAM + DTIC; 11·1 months [95% CI 7·0–13·2] for RAM).