OPTiM: a randomised phase 3 trial of talimogene laherparepvec (T-VEC) vs subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of unresected stage IIIB/C and IV melanoma (#48)
Aims: T-VEC is an oncolytic immunotherapy derived from herpes simplex virus type-1 designed to selectively replicate within tumours and produce GM-CSF to enhance systemic antitumour immune responses. OPTiM is a randomised, phase 3 trial of T-VEC or GM-CSF in patients with unresected melanoma with regional or distant metastases. We report the primary results of the first phase 3 study of oncolytic immunotherapy.
Methods: Key criteria: age ≥18 yrs; ECOG 1; unresectable melanoma Stage IIIB/C-IV; injectable cutaneous, SC, or nodal lesions; LDH ≤1.5X upper limit of normal; ≤3 non-lung visceral lesions, none ≥3 cm. Patients were randomised 2:1 to intralesional T-VEC or SC GM CSF. The primary endpoint was durable response rate (DRR), defined as objective response (OR) starting within 12 months and lasting continuously for ≥6 months. Responses were assessed by blinded central review. A planned interim analysis of overall survival (OS) was also performed.
Results: 436 patients are in the ITT set: 68% T-VEC, 32% GM-CSF. Stage distribution was: IIIB/C-30%, IVM1a-27%, IVM1b-21%, IVM1c-22%. OR rate (95% CI) with T-VEC was 26% (21% 32%) with 11% complete responses (CR), and with GM-CSF was 6% (2% 10%) with 1% CR. DRR (95% CI) for T-VEC was 16% (12% 21%) and 2% (0% 5%) for GM-CSF, p<0.0001. Interim OS favoured the T-VEC arm; HR (95% CI): 0.79 (0.61 1.02). Most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. No ≥grade 3 AE occurred in ≥3% of patients in either arm.
Conclusions: T-VEC demonstrated a statistically significant improvement in DRR over GM-CSF in patients with unresectable Stage IIIB-IV melanoma and a tolerable safety profile; an interim analysis showed a trend toward improved OS. T-VEC represents a novel potential treatment option for metastatic melanoma.
Andtbacka R et al. J Clin Oncol 31, 2013 (suppl;abstr LBA9008). Reused with permission. ©2013 American Society of Clinical Oncology. All rights reserved.