Abstract

Background

Preclinical studies suggest that BRAF inhibitors enhance anti-tumor immunity and antigen presentation. Combination BRAF inhibition with immunotherapy is an appealing therapeutic approach. We sequenced vemurafenib with HD IL-2 in patients with BRAF-mutated metastatic melanoma to improve long term outcomes.

Methods

Eligible patients were HD IL-2 eligible with metastatic BRAF V600 mutated melanoma. Cohort 1 was treatment naïve and received vemurafenib 960 mg BID for 6 weeks before HD IL-2. Cohort 2 received vemurafenib for 7–18 weeks before enrollment. Both cohorts received HD IL-2 at 600,000 IU/kg every 8 h days 1–5 and days 15–19. The primary objective was to assess complete responses (CR) at 10 weeks ±3 (assessment 1) and 26 weeks ±3 (assessment 2) from the start of HD IL-2.

Results

Fifty-three patients were enrolled, (cohort 1, n = 38; cohort 2, n = 15). Of these, 39 underwent assessment 1 and 15 assessment 2. The CR rate at assessment 1 was 10% (95% CI 3–24) for both cohorts combined, and 27% (95% CI 8–55) at assessment 2. Three-year survival was 30 and 27% for cohort 1 and cohort 2, respectively. No unexpected toxicities occurred. A shift in the melanoma treatment landscape during this trial adversely affected accrual, leading to early trial closure.

Conclusions

Vemurafenib in sequence with HD IL-2 did not change the known toxicity profile for either agent. Lower than expected response rates to vemurafenib were observed. Overall response rates and durability of responses appear similar to that observed with HD IL-2 alone.

Trial registration

NCTN, NCT01683188. Registered 11 September 2012, http://www.clinicaltrials.gov/NCT01683188

Details

Title
A multi-center phase II study of high dose interleukin-2 sequenced with vemurafenib in patients with BRAF-V600 mutation positive metastatic melanoma
Author
Clark, Joseph I  VIAFID ORCID Logo  ; Singh, Jatinder; Ernstoff, Marc S; Lao, Christopher D; Flaherty, Lawrence E; Logan, Theodore F; Curti, Brendan; Agarwala, Sanjiv S; Taback, Bret; Cranmer, Lee; Lutzky, Jose; Luna, Theresa L; Aung, Sandra; Lawson, David H
Section
Research Article
Publication year
2018
Publication date
Jul 2018
Publisher
BMJ Publishing Group LTD
e-ISSN
20511426
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2638088284
Copyright
© 2018 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.