1526P - Anti-PD-L1/TGF-βRII fusion protein SHR-1701 combined with nab-paclitaxel and gemcitabine in previously untreated patients with locally advanced or metastatic pancreatic cancer: A multicenter, phase Ib/II study

Background

The nab-paclitaxel plus gemcitabine (AG) is the standard first-line chemotherapy of advanced pancreatic cancer with limited efficacy. Dual inhibition of PD-L1 and TGF-β is a promising therapeutic strategy, as the key pathways have independent and complementary immunosuppressive functions. SHR-1701 is a bi-functional agent which can simultaneously block both the PD-1/PD-L1 and TGF-β/TGF-βR signaling within the TME. Until now, it is obscure for the clinical value of SHR1701 in pancreatic cancer. This phase 1b/2 clinical trial was designed to evaluate the antitumor activity and safety of SHR-1701 combined with AG chemotherapy regimen in patients with previously untreated locally advanced and metastatic pancreatic cancer.

Methods

Patients received SHR-1701 (30 mg/kg) on day 1 plus gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on day 1 and 8 of each 3-week cycle by intravenous infusion. The primary endpoint of phase 1b part was recommended phase 2 dose (RP2D). In the phase 2 part, the primary endpoint was objective response rate (ORR) per investigator according to RECIST v1.1.

Results

No dose-limiting toxicities (DLTs) were observed among the first 6 patients; the RP2D of SHR-1701 was 30 mg/kg. As of Mar 31, 2023, 56 patients were enrolled. Median follow-up was 10.3 months (range, 0.2-24.7). ORR was 32.1% (95% CI, 20.3-46.0). Median progressive-free survival (PFS) was 5.6 months (95% CI, 4.3-6.6), and median overall survival (OS) was 10.3 months (95% CI, 8.8-12.3). Treatment-related adverse events of grade ≥3 were reported in 27 (48.2%) patients with the most common being decreased neutrophil count. Patients with PD-L1 TPS ≥1% showed a higher ORR (66.7% vs. 25.0%), as well as longer median PFS (6.3 vs. 5.3 months) and median OS (18.8 vs. 9.9 months). Fibrosis-associated signatures (such as ECM-myCAF and IL-iCAF) and pSMAD2/3 level were associated with anti-tumor activity.

Conclusions

SHR-1701 combined with AG showed positive antitumor activity and controllable safety in advanced pancreatic cancer.

Clinical trial identification

NCT04624217.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.