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E3611-A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma. Clin Cancer Res 2019 01 15;25(2):524-532



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2-s2.0-85060063447   4 Citations


PURPOSE: Interferon-α favors a Th1 shift in immunity, and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects, leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy, supporting this hypothesis.

PATIENTS AND METHODS: E3611 followed a 2-by-2 factorial design (A: ipi10+HDI; B: ipi10; C: ipi3+HDI; D: ipi3) to evaluate (i) no HDI versus HDI (across ipilimumab doses) and (ii) ipi3 versus ipi10 (across HDI status). We hypothesized that median progression-free survival (PFS) would improve from 3 to 6 months with HDI versus no HDI and with ipi10 versus ipi3.

RESULTS: For eligible and treated patients (N = 81) at a median follow-up time of 29.8 months, median PFS was 4.4 months [95% confidence interval (CI), 2.7-8.2] when ipilimumab was used alone and 7.5 months (95% CI, 5.1-11.0) when HDI was added. Median PFS was 3.8 months (95% CI, 2.6-7.5) with 3 mg/kg ipilimumab and 6.5 months (95% CI, 5.1-13.5) with 10 mg/kg. By study arm, median PFS was 8.0 months (95% CI, 2.8-20.2) in arm A, 6.2 months (95% CI, 2.7-25.7) in B, 5.7 months (95% CI, 1.5-11.1) in C, and 2.8 months (95% CI, 2.6-5.7) in D. The differences in PFS and overall survival (OS) did not reach statistical significance. Adverse events were consistent with the known profiles of ipilimumab and HDI and significantly higher with HDI and ipi10.

CONCLUSIONS: Although PFS was increased, the differences resulting from adding interferon-α or a higher dose of ipilimumab did not reach statistical significance and do not outweigh the added toxicity risks.

Author List

Tarhini AA, Lee SJ, Li X, Rao UNM, Nagarajan A, Albertini MR, Mitchell JW Jr, Wong SJ, Taylor MA, Laudi N, Truong PV, Conry RM, Kirkwood JM


Stuart J. Wong MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Kaplan-Meier Estimate
Middle Aged
Neoplasm Metastasis
Neoplasm Staging
Treatment Outcome
Young Adult
jenkins-FCD Prod-468 69a93cef3257f26b866d455c1d2b2d0f28382f14