1090 - Talimogene laherparepvec (T-VEC) in combination (combo) with ipilimumab (ipi) versus ipi alone for advanced melanoma: 3-year landmark analysis of a randomized, open-label, phase 2 trial

Background

This is the first and only randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor in advanced melanoma. Previously, the study met its primary endpoint: the combo of T-VEC plus ipi resulted in a significantly higher objective response rate (ORR) vs. ipi alone (39% vs. 18%; odds ratio, 2.9; 95% Cl, 1.5–5.5; P = 0.002) (Chesney et al. J Clin Oncol. 2017). Here, we present results from the 3-year landmark analysis.

Methods

Pts with unresectable, stages IIIB to IV melanoma were randomized 1:1 to receive the combo or ipi alone. T-VEC was injected intratumorally on day 1 of wk 1 at 10⁶ plaque-forming units (PFU)/mL followed by subsequent doses at 10⁸ PFU/mL on day 1 of wk 4, and every 2 wks thereafter. Intravenous ipi (3 mg/kg) was given every 3 wks starting on day 1 of wk 6 for up to 4 doses. Response was assessed by investigators per immune-related response criteria every 12 wks until disease progression. The primary endpoint was ORR; key secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. This analysis occurred 36 months (mos) after the last pt was randomized.

Results

198 pts were randomized (98 to combo; 100 to ipi). As of 25 Feb 2019, the median follow-up time was 40.0 mos in the combo arm and 34.3 mos in the ipi arm. ORR was significantly higher with the combo vs. ipi alone (36.7% vs. 16.0%; odds ratio, 3.0; 95% CI, 1.6 to 6.0; P = 0.002). Median PFS was 13.5 mos with combo and 4.5 mos with ipi (hazard ratio, 0.78; 95% Cl, 0.55–1.11; P = 0.159). Median OS was not reached in either arm (HR, 0.85; 95% CI, 0.55–1.32; P = 0.480). 45 pts (45.9%) in the combo arm and 64 pts (64%) in the ipi arm received subsequent anticancer therapy, with the median time from randomization to the first subsequent therapy being 27.7 mos and 8.3 mos, respectively. No new safety signals were detected.

Conclusions

At the 3-year follow-up, T-VEC plus ipi combo continued to provide durable and statistically superior ORR compared with ipi alone. PFS was numerically longer with the combo than ipi. Survival is likely confounded by subsequent anticancer therapies (NCT01740297).

Clinical trial identification

NCT01740297, release date December 4, 2012.

Editorial acknowledgement

Medical writing assistance was provided by Yang Li (Amgen Inc).

Legal entity responsible for the study

Amgen.

Funding

Amgen.

Disclosure

J.A. Chesney: Advisory / Consultancy, Travel / Accommodation / Expenses: Replimune; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Licensing / Royalties, Patents, Royalties, and Other Intellectual Property: University of Louisville. I. Puzanov: Advisory / Consultancy: 4SC; Advisory / Consultancy: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck. P. Singh: Advisory / Consultancy: AstraZeneca. M. Milhem: Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Amgen; Advisory / Consultancy: Trieza; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Biontech. O. Hamid: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi/Regeneron; Research grant / Funding (institution): Arcus; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): CytomX; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): Parker; Research grant / Funding (institution), Additional research funding for institution: Polynoma. : Pfizer. M.I. Ross: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Provectus; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Castle Biosciences. P. Friedlander: Advisory / Consultancy: Regeneron; Advisory / Consultancy: Puma Biosciences; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Aspyrian Therapeutics; Shareholder / Stockholder / Stock options: Incyte; Shareholder / Stockholder / Stock options: Clovis; Shareholder / Stockholder / Stock options: Merrimack Phamaceuticals; Shareholder / Stockholder / Stock options: Allergan. C. Garbe: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Neracare; Honoraria (self), Advisory / Consultancy: Philogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi. T. Logan: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Acceleron; Research grant / Funding (institution): Abbott; Research grant / Funding (institution): Abraxis; Research grant / Funding (institution): Argos; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Aveo; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Immatics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Synta; Research grant / Funding (institution): Threshold; Research grant / Funding (institution): Millenium; Honoraria (self), Research grant / Funding (institution), Additional research funding to institution disclosure: Tracon, Cerulean, EMD Serono, Macrogenic, Peloton, Iovance, MedImmune, Dynavax. : Prometheus. A. Hauschild: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD/Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Provectus; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Philogen; Advisory / Consultancy, Research grant / Funding (institution): Regeneron; Advisory / Consultancy: OncoSec. C. Lebbe: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self): Pierre-Fabre; Honoraria (self): Pfizer; Honoraria (self): Incyte; Officer / Board of Directors: Aventis. M. Yi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. A. Sharma: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. J.M. Mehnert: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EMD Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Polynoma; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Incyte. All other authors have declared no conflicts of interest.