Early safety from a phase 1, multicenter, open-label, dose de-escalation study of talimogene laherparepvec (T-VEC) in Japanese patients (pts) with...

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Melanoma
Anticancer Agents
Clinical Research
Presenter Naoya Yamazaki
Citation Annals of Oncology (2018) 29 (suppl_9): ix105-ix108. 10.1093/annonc/mdy439
Authors N. Yamazaki1, H. Koga2, T. Kojima3, A. Tsutsumida4, K. Namikawa4, M. Yi5, K. Mera6, C. Pickett-Gies7
  • 1Department Of Dermatology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2Department Of Dermatology, Shinshu University School of Medicine, Matsumoto/JP
  • 3Division Of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 4Department Of Dermatologic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 5Biostatistics, Amgen Inc., Thousand Oaks/US
  • 6Development, Oncology, Amgen Astellas BioPharma K.K., Tokyo/JP
  • 7Clinical Development, Amgen Inc., Thousand Oaks/US

Abstract

Background

T-VEC, a genetically modified herpes simplex virus-1, is the first FDA-approved oncolytic viral therapy designed to preferentially replicate in tumors, lyse tumor cells, produce granulocyte-macrophage colony-stimulating factor, and stimulate antitumor immune responses via enhanced antigen presentation and activation of effector T cells. In the phase 3 OPTiM trial, T-VEC monotherapy demonstrated a tolerable safety profile and resulted in a durable response rate (DRR, partial response or complete response [CR] lasting continuously ≥ 6 mos) of 16.3% and a CR rate of 10.8% in pts with advanced MEL. This phase 1 study evaluates the safety and antitumor activity of T-VEC in Japanese pts with unresectable stage IIIB-IV MEL.

Methods

The primary endpoints are pt incidence of dose-limiting toxicities (DLTs) and DRR. Eligible pts are ≥ 18 years of age with histologically confirmed stage IIIB-IVM1c MEL, may have received prior systemic anticancer therapy, and must have at least 1 injectable lesion. Initially, 6 DLT-evaluable pts will be treated at the FDA/EMA-approved dose 1 (≤ 4.0 mL of 106 PFU/mL T-VEC on day 1, followed by ≤ 4.0 mL of 108 PFU/mL 3 wks later and then every 2 wks). Upon demonstration of safety, an additional 12 pts will be enrolled to obtain additional safety data. If dose 1 is declared unsafe, a de-escalated dose will be evaluated by the same procedures.

Results

6 DLT-evaluable pts were enrolled and treated at dose 1: median age was 52; 5/6 were female; and 3 discontinued treatment (2 due to disease progression). 5 pts received prior systemic therapy for metastatic disease. No DLT was observed during the DLT evaluation period. The most common adverse events (AEs) were pyrexia (pt incidence, 4/6) and chills (2/6). 4 serious AEs were reported in 2 pts: infectious enteritis, worsening of benign prostatic hyperplasia (only SAE considered treatment-related), epiglottitis, and pneumonia.

Conclusions

There was no DLT in 6 evaluable pts. Most AEs were grade 1 or 2 and consistent with those observed in OPTiM. Dose 1 was deemed tolerable, and an additional 12 pts will be enrolled for further evaluation of safety and efficacy of dose 1.

Editorial acknowledgement

Yang Li.

Clinical trial identification

NCT number: NCT03064763.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

N. Yamazaki: Research grants: Novartis, MSD, Ono, and BMS; Speaker bureau: Novartis, Takeda, and MSD. T. Kojima: Research grants: MSD, Ono Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Astellas Amgen BioPharma, Oncolysis BioPharma. K. Namikawa: Honoraria: Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Novartis Pharmaceutical, Toray industries, and Takara Bio, outside the submitted work. M. Yi: Employee and own stock: Amgen Inc. K. Mera: Employee: Amgen Astellas Biopharma; Owns stock: Amgen Inc. C. Pickett-Gies: Employed by and owns stock in Amgen Inc. All other authors have declared no conflicts of interest.