AN0025 is a small molecule EP4 antagonist designed to modulate the tumor microenvironment. In-licensed from Eisai in January 2018, we have exclusive rights and license to develop and commercialize AN0025 globally, excluding Japan, Korea, Taiwan and some Southeast Asian Countries. AN0025 and radiotherapy (RT) combination treatment demonstrated improved antitumor activity and antitumor memory T-cell response in mice compared with RT monotherapy. In June 2024, the strategic prioritization of clinical programs for AN0025 has been established, with a focus on its combination with CRT across various indications via investigator-initiated trials (“IIT”):
ARTEMIS (Augmenting RadioTherapy in REctal Cancer to Minimise Invasive Surgery) Phase II study of Preoperative AN0025 and Radiotherapy/Chemoradiotherapy Combination in Rectum Cancer
ARTEMIS is a randomized phase II trial for patients with moderate to high-risk rectal cancer where pre-operative chemo-RT is a standard treatment option and suitable for organ preservation. Patients are randomized 1:1 between 1) standard of care long-course chemo-RT (LCCRT) or short-course chemo-RT (SCCRT) based on clinician choice, and 2) standard of care LCCRT or SCCRT based on clinician choice, with the addition of immunotherapy agent AN0025. Both arms will also receive total neoadjuvant treatment (TNT) in the form of FOLFOX or CAPOX, based on clinician choice. The primary endpoint is Clinical Complete Response rate at 6 months post start of radiotherapy. A total of 140 patients will be randomized. In May 2024, the first patient was dosed. Preliminary safety and efficacy data, including a futility analysis, are expected by the end of 2025.
Phase Ib study of Preoperative AN0025 and Radiotherapy/Chemoradiotherapy Combination in Rectum Cancer (NCT03152370)
We completed a Phase Ib study to evaluate AN0025 in combination with RT/Chemoradiotherapy (CRT) for neoadjuvant treatment of rectal cancer where primary resection without RT/CRT is unlikely to achieve clear margins. We presented encouraging interim results2 of this trial at the European Society for Medical Oncology (“ESMO”) in October 2019. In particular, the combination therapy with AN0025 and RT/CRT reported an exceptionally high clinical complete response (“cCR”) of 20%, indicating surgery is no longer required for these patients. Additionally, a high pathologic complete response (“pCR”) of 16% was observed, indicating that no residual tumors were found in these patients after surgery. The promising results from the Phase Ib study warrants further development, leading to the initiation of the ARTEMIS study mentioned above.
Phase Ib study of AN0025 and Definitive Chemoradiotherapy (dCRT) Combination in Unresectable Locally Advanced or Locally Recurrent Esophageal Cancer (NCT03152370)
This Phase Ib study includes a dose escalation phase followed by an expansion phase to evaluate the safety, tolerability, and feasibility of AN0025 plus dCRT for unresectable locally advanced or locally recurrent EC or esophagogastric junction cancer. We presented encouraging interim results3,4 of this trial at ASCO 2024 and ESMO 2024. No dose-limiting toxicity occurred at either dose level, and the maximum tolerated dose was not reached. In particular, the 15-month progression-free survival rate was 73% and the overall response rate was 82%. Building upon the promising results, we are continuing to enroll additional patients.
Reference
1. J Immunother Cancer, 2020 8(1): e000222 (pdf).
2. A Phase 1b Study of E7046 (AN0025) in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Rectal Cancer, ESMO 2019 (pdf).
3. AN0025 in Combination with Definitive Chemoradiotherapy (dCRT) in Unresectable Locally Advanced or Locally Recurrent Esophageal Cancer (EC): A Single-Arm, Open-Label, Multicenter, Phase Ib Study, ASCO 2024 (pdf).
4. A Phase Ib Study of AN0025 in Combination With Definitive Chemoradiotherapy (dCRT) in Unresectable Locally Advanced or Locally Recurrent Esophageal Cancer (EC), ESMO 2024 (pdf).
