OPTiM: A randomized phase III trial to evaluate the efficacy and safety of talimogene laherparepvec (T-VEC) compared with subcutaneously (sc) administered GM-CSF for the treatment (tx) of unresectable stage IIIb, IIIc, and IV melanoma.
TPS8604 Background: T-VEC (formerly OncoVEXGM-CSF) is an oncolytic HSV1 that selectively replicates in tumors. The proposed MOA includes lytic destruction of injected tumors and induction of a systemic anti-tumor immune response enhanced by local GM-CSF expression. Intratumoral T-VEC tx in a 50-patient (pt) ph II study in advanced melanoma (Stage IIIc-IVM1c) was well tolerated and achieved a high rate and duration of response, including 20% CR (Senzer et al., JCO 2009; 27: 5763-71). As immune effects may be delayed, progressive disease (PD) often occurred before response. Based on the ph II data, a randomized ph III trial of T-VEC in unresectable melanoma (the OPTiM study; clinical trials registry NCT00769704) was designed taking into account the response patterns seen with T-VEC and other immunotherapeutic agents. T-VEC is the first "armed" oncolytic agent to enter pivotal testing worldwide. Methods: OPTiM compares the efficacy and safety of intratumoral T-VEC to sc GM-CSF in 430 pts with treated or untreated unresectable Stage IIIb-IVM1c melanoma stratified by typical prognostic factors. Pts are randomized 2:1 to T-VEC (priming dose of up to 4 x 106 pfu intratumorally then 3 wks later by up to 4 x 108 pfu Q2W) or GM-CSF 125 µg/m2 qd sc x 14 days every 28 days. Key eligibility criteria are ≥ 18 yrs old, ECOG 0-1, and at least 1 injectable cutaneous, sc, or nodal tumor. The primary endpoint is durable response rate (DRR: CR or PR continuously maintained for ≥ 6 mo initiating within 12 mo of starting tx; secondary endpoints include OS. Responses are subject to independent review. Pts are treated until wk 24, even with PD. Thereafter pts are treated until clinically significant PD, CR, or for 1 yr. The study has 90% power to show a 10% difference in DRR with 2-sided Fisher Exact Test (α = 5%). Enrollment closed in July 2011 with 439 pts randomized in the US, UK, S Africa, and Canada. Interim analysis in Dec 2010 on 75 pts on study > 9 mo concluded that the study should continue. Results are expected during 2012. Conclusions: T-VEC provides a novel potential tx for melanoma. This pivotal ph III study is expected to report during 2012.