This is the first randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor for advanced melanoma.
At the 3-year follow-up, the combination ( combo ) of Talimogene laherparepvec ( T-VEC; Imlygic ) and Ipilimumab ( Yervoy ) has demonstrated durable and statistically superior objective response rate ( ORR ) over Ipilimumab alone ( 36.7% versus 16.0%; odds ratio, OR=3.0; 95% Cl, 1.6–6.0; P = 0.002 ).
Complete response ( CR ) rate was 21.4% with the combination and 6.0% with Ipilimumab.
Median overall survival ( OS ) was not reached in either arm.
In this post hoc analysis, researchers have utilized the 3-year landmark data to explore the relationship between complete response and overall survival in the combo arm.
Patients with unresectable, stage IIIB-IV melanoma were randomized 1:1 to receive Talimogene laherparepvec + Ipilimumab or Ipilimumab alone.
Talimogene laherparepvec was administered intratumorally on day 1 of week 1 at 106 plaque-forming units ( PFU )/mL followed by subsequent doses at 108 PFU/mL on day 1 of week 4, and every 2 weeks thereafter.
Ipilimumab ( 3 mg/kg ) was given every 3 weeks starting on day 1 of week 6 for up to 4 doses.
Response was assessed by investigators per immune-related response criteria every 12 weeks until disease progression.
The primary endpoint was objective response rate; key secondary endpoints were overall survival, progression-free survival ( PFS ), and safety.
198 patients were randomized ( 98 to Talimogene laherparepvec + Ipilimumab; 100 to Ipilimumab ). As of February 25, 2019, the median follow-up time was 40.0 months ( range: 0.2–63.7 ) for the combo arm.
Among 98 patients who received Talimogene laherparepvec + Ipilimumab, 21 ( 21.4% ) had a best overall response of CR including 8 who converted from an initial partial response ( PR ), 15 ( 15.3% ) had PR, 19 ( 19.4% ) had stable disease, 30 ( 30.6% ) had progressive disease, and 13 ( 13.2% ) were unevaluable.
Of 21 patients achieving CR, 17 ( 81% ) had ECOG status of 0, 16 ( 76.2% ) had stage IIIB-IVM1a disease, and 16 ( 76.2% ) had no visceral metastases.
Median duration of CR was not reached ( range: 5.4[+]–58.2[+] months ); 19 of 21 complete responses lasted more than 6 months.
The baseline tumor burden was lower in patients with CR than in those with non-CR.
Median overall survival was not reached in patients with CR ( range: 25.1[+]–63.7[+] months ) and was 47.6 months ( range: 0.2[+]– 63.7[+] months ) in patients with non-CR ( Log-rank P = 0.0005 ). The Kaplan–Meier estimated 3-year OS rate was 100.0% for patients with CR and 52.3% for those with non-CR.
In conclusion, CR rate was higher with Talimogene laherparepvec plus Ipilimumab than with Ipilimumab alone in patients with advanced melanoma ( 21.4% vs 6.0% ).
In the combo arm, CR was associated with prolonged overall survival, and patients with CR tended to have better ECOG performance status, earlier-stage disease, and lower baseline tumor burden, as compared with those with non-CR. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020