Sintilimab ( Tyvyt ), an anti-PD-1 antibody, in combination with Pemetrexed and Platinum has shown promising activity for non-squamous non-small cell lung cancer ( nsqNSCLC ) in a phase 1b study.
The randomized, double-blind, phase 3 study ( ORIENT-11 ) has compared the efficacy and safety of Sintilimab with placebo, in combination with such chemotherapy.
Previously untreated patients with locally advanced or metastatic ( ineligible for local therapy ) nsqNSCLC without sensitizing EGFR or ALK mutations were enrolled and randomized 2:1 to receive Sintilimab or placebo intravenously with Pemetrexed and Platinum for 4 cycles, followed by Sintilimab or placebo with Pemetrexed as maintenance therapy.
Stratification factors included gender, Platinum ( Cisplatin versus Carboplatin ), and PD-L1 expression ( TPS, 1% or more vs less than 1% ).
Conditional crossover or treatment beyond disease progression were allowed at the discretion of investigators.
The primary endpoint was progression-free survival ( PFS ) by independent radiologic review committee ( IRRC ).
From Aug. 23, 2018 to Jul. 30, 2019, 397 patients were enrolled and randomized to Sintilimab group ( n=266 ) and Placebo group ( n=131 ).
The baseline characteristics were balanced between two groups.
With a median follow-up of 8.9 months, 75.3% ( 198/263 ) of planned PFS events has been achieved.
The median progression-free survival was significantly longer in Sintilimab group than in Placebo group ( 8.9 vs 5.0 months, HR, 0.482, 95% CI, 0.362 to 0.643, P less than 0.00001 ).
The median overall survival ( OS ) has not been reached, but showed a nominally significant improvement for Sintilimab group ( HR, 0.609, 95% CI, 0.400 to 0.926, P=0.01921 ).
The PFS benefit from Sintilimab and chemotherapy combination was observed in all subgroups of PD-L1 TPS.
The confirmed ORR was 51.9 % ( 95% CI, 45.7% to 58.0% ) in Sintilimab group and 29.8% ( 95% CI, 22.1% to 38.4% ) in Placebo group.
The incidence of greater than or equal to 3 grade adverse events was 61.7% in Sintilimab group and 58.8% in Placebo group.
The immunerelated adverse effects, by investigators before unblinding, was 43.2% in Sintilimab group and 36.6% in Placebo group.
No new safety signals were observed.
In conclusion, the addition of Sintilimab to chemotherapy significantly improved progression-free survival with acceptable safety profile among locally advanced or metastatic nsqNSCLC patients. ( Xagena )
Source: IASLC Virtual Presidential Symposium, 2020