LBA5 - A phase 2 study of neoadjuvant SHR-1701 with or without chemotherapy (chemo) followed by surgery or radiotherapy (RT) in stage III unresectable NSCLC (uNSCLC)

Background

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.

Methods

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).

Results

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. Table: LBA5

Efficacy by study arm

Conclusions

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.

Clinical trial identification

NCT04580498.

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals, Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals, Co., Ltd.

Disclosure

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.