1322P - A phase II trial of autologous cytokine-induced killer (CIK) therapy plus toripalimab with or without chemotherapy as first-line treatment in advance NSCLC

Background

PD-1 inhibitors plus chemotherapy is currently the mainstream first-line treatment options for advanced driver-negative NSCLC and still remained challenging to treat effectively. Cytokine-induced killer (CIK) therapy has shown promising synergistic antitumor efficacy in many studies, especially in combination with PD-1 inhibitors. Here we conducted a prospective phase Ⅱ study to investigate the clinical effects and safety of CIK therapy plus PD-1 with or without chemotherapy in NSCLC.

Methods

Pts with treatment-naive, PD-L1≥1%, advanced NSCLC without EGFR/ALK mutations were randomly assigned 1:1 into two arms. Arm A received toripalimab + CIK + chemotherapy. Arm B received toripalimab + CIK only. Treatment continued until disease progression or unacceptable toxicity. The primary endpoints were safety and progression free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and overall survival(OS). Exploratory analyses were performed to identify potential biomarkers.

Results

A total of 40 pts (median age of 64yr, 60% with PD-L1≥50%) were randomized. 19 pts in Arm A(1pts withdraw consensus and did not receive at least one full cycle treatment) and 20 pts in Arm B were analyzed. After a median follow-up of 18.1m, median PFS in Arm A was significantly longer than Arm B (20.0m vs. 6.0m, HR = 0.335 [95% CI: 0.155-0.725], P= 0.0038). The mPFS in Arm A was also remarkably better than historical data of 8.9m which is the standard of care (toripalimab + chemotherapy) for first-line NSCLC. ORR was 47.37%(95% CI: 24.45%-71.14%) for Arm A and 60%(95% CI: 36.05%-80.88%) for Arm B, and DCR was 100%(95% CI: 82.35%-100.00%) for Arm A and 90%(95% CI: 68.30%-98.77%) for Arm B, with a trend toward longer mDOR with arm A(16.7m vs 6.5m). The median OS was not reached in Arm A and 17.0m in Arm B (HR = 0.382 [95% CI: 0.142-1.027], P = 0.0479). Pts received ≥5 cycles CIK infusion had longer mPFS than those received <5 cycles (P <0.0001). No new safety signals arose.

Conclusions

These promising results of CIK + toripalimab + chemotherapy may contribute to a paradigm shift in first-line treatment of advanced NSCLC. Follow up for survival is ongoing.

Clinical trial identification

ChiCTR2000035573.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Shanghai Junshi Biosciences, Shanghai, China.

Disclosure

S. Chen, M. Zhang: Financial Interests, Personal, Full or part-time Employment: Shanghai Junshi Biosciences. All other authors have declared no conflicts of interest.