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.
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".