Consolidation immunotherapy (IO) after chemoradiation is the standard of care for stage III uNSCLC. Addition of IO-based induction therapy may further improve outcome, partly by enabling surgery. SHR-1701 is a novel anti-PD-L1/TGFβRII fusion protein. We assessed neoadjuvant SHR-1701 ± chemo, followed by surgery or RT in untreated stage III uNSCLC without EGFR/ALK alterations.
Pts were given 3 cycles of neoadjuvant SHR-1701 (30 mg/kg Q3W) ± chemo (paclitaxel 175 mg/m2 Q3W + carboplatin AUC=5 Q3W). Pts with PD-L1 TPS <50% received combo-therapy (arm A) and those with PD-L1 TPS ≥50% were randomized (1:1) to receive combo-therapy (arm B) or SHR-1701 alone (arm C). After assessment by MDT, pts received surgery or definitive RT (60 Gy/30 fractions) + concurrent cisplatin (30 mg/m2 QW), followed by SHR-1701 for 16 cycles. The primary endpoints were post-induction ORR and event-free survival (EFS).
107 pts were enrolled (arm A/B/C, n=88/9/10; median age, 59 y; squamous NSCLC, 76.6%; stage IIIA/B/C, 25.2%/43.9%/29.9%). In all pts, the post-induction and best overall ORR were 56.1% (95% CI 46.2-65.7) and 70.1% (60.5-78.6). mEFS was 18.2 mo (95% CI 11.8-not reached [NR]). Efficacy by study arm is shown in Table 1. 27 (25.2% of 107; baseline stage IIIA/B/C, 37.0%/44.4%/18.5%) pts underwent surgery (lobectomy/bilobectomy/pneumonectomy, 88.9%/7.4%/3.7%); all achieved R0 resection. Among them, 12 (44.4%) MPR and 7 (25.9%) pCR were recorded. Nodal downstaging was seen in 14 pts (51.9%; pN2 to pN0/1, 8/14 [57.1%]; pN3 to pN0-2, 6/9 [66.7%]). mEFS was NR in resected pts. Grade ≥3 TRAEs occurred in 77 (72.0%) pts; all with frequency ≥10% were hematotoxicities. No new safety signals were identified. Efficacy by study arm
Arm A (n=88) Arm B (n=9) Arm C (n=10) Arm A+B (n=97) All pts (n=107) Post-induction ORR (95% CI),% 55.7 (44.7-66.3) 77.8 (40.0-97.2) 40.0 (12.2-73.8) 57.7 (47.3-67.7) 56.1 (46.2-65.7) DCR (95% CI)*,% 93.2 (85.7-97.5) 88.9 (51.8-99.7) 90.0 (55.5-99.7) 92.8 (85.7-97.0) 92.5 (85.8-96.7) Best overall ORR (95% CI),% 70.5 (59.8-79.7) 77.8 (40.0-97.2) 60.0 (26.2-87.8) 71.1 (61.0-79.9) 70.1 (60.5-78.6) mEFS (95% CI)†, mo 18.2 (11.5-NR) 11.8 (3.3-NR) NR (2.0-NR) 14.9 (11.5-NR) 18.2 (11.8-NR) Surgery conversion, n (%) 21 (23.9) 3 (33.3) 3 (30.0) 24 (24.7) 27 (25.2) *Same results for best overall DCR. †Starting from the first study dose. Data cutoff was Jul. 31, 2022.
SHR-1701 ± chemo showed promising antitumor activity with a tolerable safety profile in stage III uNSCLC. Some pts could switch from unresectable to resectable and get much better efficacy. Phase 3 investigation is warranted.
NCT04580498.
Jiangsu Hengrui Pharmaceuticals, Co., Ltd.
Jiangsu Hengrui Pharmaceuticals, Co., Ltd.
Y. Wu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb, Hengrui; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Research Grant: Boehringer Ingelheim, Roche, Pfizer, Bristol Myers Squibb. J. Shuang, L. Song, W. Shi: Financial Interests, Personal, Full or part-time Employment: Hengrui. All other authors have declared no conflicts of interest.