Introducing OPTiM

Oncovex (GM-CSF) Pivotal Trial in Melanoma

Study design

Oncovex (GM-CSF) Pivotal Trial in Melanoma (OPTiM) was a phase 3, multicenter, open-label study of 436 stage IIIB, IIIC, and IV patients (previously treated and untreated). Patients had injectable, unresectable melanoma and were randomized 2:1 to receive IMLYGIC® or GM-CSF.1,2,3

A total of 436 patients were randomized to receive either IMLYGIC® (talimogene laherparepvec) (n = 295) or GM-CSF (n = 141).1

INJECTABLE, UNRESECTABLE

Stage IIIB, IIIC, and IV melanoma1 (N = 436)

RANDOMIZED 2:11,3

IMLYGIC® intralesional injection (n = 295)
GM-CSF subcutaneous injection (n = 141)

Patients were to be treated for a minimum of 6 months unless other treatment was required or until no injectable lesions were remaining. During this period, treatment could continue despite an increase in size in existing lesion(s) and/or development of new lesion(s), unless the patient developed intolerable toxicity or the investigator believed that it was in the best interest of the patient to stop treatment or to be given other therapy for melanoma.1

After 6 months of treatment, patients were to continue treatment until clinically relevant disease progression (ie, disease progression associated with a decline in performance status and/or alternative therapy was required in the opinion of the investigator), up to 12 months. Patients experiencing a response at 12 months after the start of treatment could continue treatment for up to an additional 6 months, unless there were no remaining injectable lesions or disease progression. All patients were to be followed for survival status for at least 36 months.1

Eligibility criteria

Inclusion/exclusion criteria

Patient characteristics employed in the phase 3 clinical trial are the following1-4:

Key Inclusion
Criteria
  • Adults aged ≥ 18 years
  • Previously treated and untreated not surgically resectable stage IIIB, IIIC, or IV disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Injectable disease (ie, suitable for direct injection or through the use of ultrasound guidance)
  • Serum lactate dehydrogenase (LDH) levels ≤ 1.5 × upper limit of normal (ULN)
  • At least 1 melanoma lesion ≥ 10 mm in diameter or lesions that in aggregate had a total diameter of ≥ 10 mm
Key Exclusion
Criteria
  • Clinically active cerebral or any bone metastases
  • More than 3 visceral metastases (not including lung metastases or nodal metastases associated with visceral organs)
  • Primary ocular or mucosal melanoma
  • Evidence of immunosuppression
  • Open herpetic skin lesions
  • Patients requiring intermittent or chronic treatment with an antiviral agent or high-dose steroids

Select baseline characteristics

Select baseline demographics and clinical characteristics3

Chart of baseline characteristics of patients

Chart of baseline characteristics of patients

Endpoints

Primary endpoint1

The major efficacy outcome in the trial was durable response rate (DRR).

  • DRR: defined as the percent of patients with a CR or PR maintained continuously for a minimum of 6 months1,*
    • CR: disappearance of all evidence of tumor3
    • PR: ≥ 50% reduction in the sum of the products of the perpendicular diameters of all measurable tumors at the time of assessment, as compared to baseline3

*Tumor responses determined using modified World Health Organization (WHO) criteria by a blinded, independent Endpoint Assessment Committee (EAC).3,4

IMLYGIC® was injected into cutaneous, subcutaneous, or nodal melanoma lesions and was not injected into visceral lesions.

Secondary endpoints1

Key secondary endpoints3:

  • Median Time to Response
    • The median time to response was 4.1 months (range: 1.2 to 16.7 months) in the IMLYGIC® arm1
  • Overall Survival
    • There was no statistically significant difference in overall survival between the IMLYGIC® and the GM-CSF arms1

REFERENCES

  1. IMLYGIC® (talimogene laherparepvec) Prescribing Information, BioVex, Inc., a subsidiary of Amgen Inc.
  2. Kaufman HL, Bines SD. OPTiM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. Future Oncol. 2010;6:941-949.
  3. Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780-2788.
  4. Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(suppl Clinical Study Protocol):doi:10.1200/JCO.2014.58.3377.