Abstract 50P
Background
Emerging data suggest that an immune checkpoint inhibitor in combination with chemotherapy is a reasonable strategy for advanced biliary tract cancer (aBTC). Apatinib, an oral TKI selectively targeting VEGFR2 has been shown to reshape the immune microenvironment and enhance the efficacy of camrelizumab (an anti-PD-1 antibody) in several cancers. We therefore designed this study to explore the efficacy and safety of apatinib plus Cam and GP in aBTC and especially the optimal dose of apatinib in this strategy.
Methods
This prospective, 2-part, dose escalation and expansion study enrolled patients (pts) with aBTC. Pts would receive Cam (200mg) and GP (gemcitabine 1000mg/m2 and cisplatin 25mg/m2, iv, d1 and d8; up to 6 cycles) plus apatinib in 21-day cycles. In the phase Ib, a 3+3 dose-escalation design is used to determine the recommended phase 2 dose (RP2D) of apatinib (250 mg, qd; A: d1-d7, B: d1-d10, C: d1-d14). Phase II-dose expansion part is to evaluate the primary endpoint of objective response rate (ORR).
Results
As of April 2024, 17 pts had been treated with a median age of 56 years (range 40-71) and 12 were females. Of 9 pts in phase Ib, 7 had stable disease (SD) and 2 had partial response (PR). No DLTs were reported, and PR was only observed in cohort C. Therefore, the RP2D of apatinib in combination with Cam + GP was defined as 250 mg, d1-d14 and 8 pts were enrolled in phase II. 3 pts (37.5%) achieved PR in this phase. With a median follow-up of 3 months (range, 1-5), 6 pts remained response. Best response and the most common TEAEs are summarized in the following table. Table: 50P
| Cohort | A | B | C | Total |
| Dose frequency of apatinib (q3w) | d1-d7 | d1-d10 | d1-d14 | |
| N | 3 | 3 | 3 + 8 | 17 |
| Responses | ||||
| Objective response rate (CR + PR), n/N (%) | 1/3(33) | 2/3(67) | 5/11(45) | 8/17(47) |
| Disease control (CR + PR + SD), n/N (%) | 3/3(100) | 3/3(100) | 11/11(100) | 17/17(100) |
| TEAEs, n (%) | ||||
| Alanine aminotransferase increased | 2(67) | 3(100) | 11(100) | 16(94) |
| Aspartate aminotransferase increased | 2(67) | 3(100) | 11(100) | 16(94) |
| Platelet count decreased | 3(100) | 3(100) | 10(91) | 16(94) |
| White blood cell decreased | 2(67) | 3(100) | 9(82) | 14(82) |
| Neutrophil count decreased | 1(33) | 3(100) | 9(82) | 14(82) |
| Nausea | 2(67) | 1(33) | 7(64) | 11(65) |
| Malaise | 2(67) | 2(67) | 7(64) | 11(65) |
| Alopecia | 2(67) | 2(67) | 7(64) | 11(65) |
| Grade ≥3 | 3(100) | 3(100) | 8(73) | 14(82) |
Conclusions
The efficacy signal support apatinib 250 mg, d1-d14 as an optimal dose when in combination with GP and Cam in aBTC. This combination strategy showed modest efficacy and tolerable adverse events in aBTC. The trial is still recruiting and more data would be further analyzed and reported.
Clinical trial identification
NCT05742750.
Editorial acknowledgement
Guiqin Su, Xiaoqiang Fang (Jiangsu Hengrui Pharmaceuticals Co., Ltd.) provided editorial assistance.
Legal entity responsible for the study
The authors.
Funding
Jiangsu Hengrui Pharmaceuticals Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.
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