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 — ASN Events
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  3. 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

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)

Robert HI Andtbacka 1 , Frances Collichio 2 , Thomas Amatruda 3 , Neil Senzer 4 , Jason Chesney 5 , Keith A Delman 6 , Lynn E Spitler 7 , Igor Puzanov 8 , Susan Doleman 9 , Yining Ye 10 , Ari VanderWalde 10 , Robert Coffin 9 , Howard L Kaufman 11
  1. University of Utah Huntsman Cancer Institute, Salt Lake City, UT
  2. University of North Carolina Medical Center, Chapel Hill, NC
  3. Hubert Humphrey Cancer Center, Robbinsdale, MN
  4. Mary Crowley Cancer Research Center, Dallas, TX
  5. University of Louisville, Louisville , KY
  6. Emory University, Atlanta, Atlanta, GA
  7. Northern California Melanoma Center, San Francisco, CA
  8. Vanderbilt University, Nashville, TN
  9. Amgen, Woburn, MA
  10. Amgen Inc., Thousand Oaks, CA
  11. Rush University Medical Center, Chicago, IL

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.