1453P - A phase Ib study of AN0025 in combination with definitive chemoradiotherapy (dCRT) in unresectable locally advanced or locally recurrent esophageal cancer (EC)

Background

AN0025, a selective EP4 inhibitor, exhibits antitumor effects by regulating the distribution and function of macrophages and immunosuppressive myeloid cells in the tumor microenvironment. A previous study (NCT03152370) has demonstrated AN0025 plus CRT as neoadjuvant therapy yields encouraging antitumor efficacy in locally advanced rectal cancer.

Methods

This is a single-arm, open-label, multicenter, Phase Ib study in patients (pts) with unresectable locally advanced/locally recurrent EC or esophagogastric junction cancer. AN0025 was orally dosed for 15 weeks concurrently with dCRT (paclitaxel and carboplatin, with 50-60 Gy of radiation). From Week 17 onwards, pts would start maintenance phase with AN0025 monotherapy. The dose escalation comprised 250 and 500 mg QD dose levels. Primary objective was safety and tolerability of AN0025 + dCRT. Antitumor efficacy was evaluated per RECIST 1.1.

Results

As of 25 Apr 2024, 12 pts with esophageal squamous cell carcinoma (11 locally advanced, 1 locally recurrent) were enrolled, 5 at the 250 mg cohort and 7 at the 500 mg cohort. No DLT was observed. Weight decreased (33%) and anemia (33%) were the most common AN0025-related adverse events (AEs). Two pts (17%) had gr3 AN0025-related AEs (weight decreased and esophageal fistula). Median follow-up was 18.5 months (mos), with a maximum time on treatment of 24 mos. Among the 8 pts with measurable lesions at baseline, 1 (13%) achieved confirmed complete response (CR), 6 achieved partial response (PR), including 5 confirmed PRs, giving a confirmed overall response rate (ORR) of 75%. Disease control rate (DCR) was 92% (11/12). Median progression-free survival (PFS) was not reached, with an 18-mo PFS rate of 73%. The 18-mo overall survival (OS) rate was 82%. AN0025 exhibited linear pharmacokinetics, with no interactions observed in combination with dCRT. Accumulation ratio based on C_max of 1.26-1.64 over 8 days suggests moderate accumulation with multiple doses.

Conclusions

AN0025 in combination with dCRT was well tolerated in unresectable locally advanced/locally recurrent EC and preliminary encouraging efficacy warrants further investigation of AN0025 as an immune modulator with CRT.

Clinical trial identification

NCT05191667.

Editorial acknowledgement

Legal entity responsible for the study

Adlai Nortye Biopharma Co., Ltd.

Funding

Adlai Nortye Biopharma Co., Ltd.

Disclosure

M. Gu, T. Zhao, Y. Wang, H. Liang: Financial Interests, Personal, Full or part-time Employment: Adlai Nortye Biopharma Co., Ltd. S. Lu, X. Song: Financial Interests, Personal, Full or part-time Employment: Adlai Nortye Biopharma Co., Ltd.; Financial Interests, Personal, Stocks/Shares: Adlai Nortye Biopharma Co., Ltd. All other authors have declared no conflicts of interest.