palupiprant (AN0025) / Eisai, Adlai Nortye - LARVOL DELTA

A Trial of AN0025 With Chemoradiation Therapy in Stage III NSCLC Participants (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Rutgers, The State University of New Jersey | N=24 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

AN0025 and Chemoradiotherapy Combination in Esophageal Cancer (clinicaltrials.gov) - P1 | N=32 | Suspended | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology

Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Trial primary completion date: Sep 2024 ➔ Dec 2024

Trial primary completion date • Oncology • Solid Tumor

A phase Ib study of AN0025 in combination with definitive chemoradiotherapy (dCRT) in unresectable locally advanced or locally recurrent esophageal cancer (EC) (ESMO 2024) - P1, P1b | "AN0025 was orally dosed for 15 weeks concurrently with dCRT (paclitaxel and carboplatin, with 50-60 Gy of radiation). 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."

Combination therapy • Metastases • P1 data • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Squamous Cell Carcinoma

Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Solid Tumor

Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=63 | Recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Trial completion date: Jun 2024 ➔ Jan 2025 | Trial primary completion date: Mar 2024 ➔ Sep 2024

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

AN0025 and Chemoradiotherapy Combination in Esophageal Cancer (clinicaltrials.gov) - P1 | N=32 | Suspended | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Recruiting ➔ Suspended

Combination therapy • Metastases • Trial suspension • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology

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) - P1, P1b | "0 Gy/fraction, totally 50-60 Gy) with concurrent weekly paclitaxel and carboplatin for 4 weeks, followed by two doses of consolidation chemotherapy on Week 8 and Week 12. This Phase Ib study suggests that AN0025 plus dCRT exhibits favorable safety and encouraging preliminary efficacy in unresectable locally advanced or locally recurrent EC, warranting further investigation. Clinical trial information: NCT05191667."

Clinical • Combination therapy • Metastases • P1 data • Anemia • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Oncology • Rectal Cancer • Squamous Cell Carcinoma

Adlai Nortye Ltd. to Present Encouraging Data of the Combination of AN0025 and Definitive Chemoradiotherapy (dCRT) at ASCO 2024 (GlobeNewswire) - "Adlai Nortye...today announced that it will present encouraging preliminary data of AN0025 in combination with definitive chemoradiotherapy (dCRT) in unresectable locally advanced or locally recurrent esophageal cancer (EC) at the upcoming American Society of Cancer Oncology (ASCO) Annual Meeting to be held in Chicago from May 31 to June 4, 2024....The AN0025S0104 study is a single-arm, open-label, multicenter, Phase Ib study comprising a dose escalation phase followed by an expansion phase, aimed at evaluating the safety, tolerability, and feasibility of AN0025 plus dCRT for unresectable locally advanced or locally recurrent EC or esophagogastric junction cancer....'We look forward to joining the oncology community in Chicago and sharing updates on our cutting-edge pipeline of programs.'"

P1 data • Esophageal Cancer

Role of COX-2/PGE2/EP4 Axis-induced Macrophage Functional Activation in NSCLC Development (PubMed, Zhongguo Fei Ai Za Zhi) - "During NSCLC development, the COX-2/PGE2/EP4 axis may promote tumor progression by inducing macrophage functional activation, and EP4 may be a potential new target for tumor immunotherapy. This study provides new perspectives and ideas for in-depth exploration of the mechanisms of NSCLC development, as well as a theoretical basis for the development of new therapeutic strategies for NSCLC."

IO biomarker • Journal • Hepatology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Transplantation • CD163 • CD31 • CD86 • CDH1 • CDH2 • PECAM1

Adlai Nortye Announces First Patient Dosed in Randomized Phase II Clinical Trial of Palupiprant (AN0025) for the Treatment of Locally Advanced Rectal Cancer with Radiation Therapy (GlobeNewswire) - "Adlai Nortye Ltd...recently announced that the first patient was dosed in the Phase II clinical trial known as ARTEMIS (Augmenting RadioTherapy in REctal Cancer to Minimise Invasive Surgery). This clinical study evaluates palupiprant (AN0025), a small molecule prostaglandin E receptor 4 ('EP4') antagonist, with chemoradiotherapy and radiotherapy (total neoadjuvant therapy: ‘TNT’) ('CRT') for the treatment of rectal cancer."

Trial status • Gastrointestinal Cancer • Rectal Cancer

KEYNOTE 879: AN0025 and Pembrolizumab Combination in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Trial completion date: Nov 2025 ➔ Jan 2025 | Trial primary completion date: Apr 2025 ➔ May 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=63 | Recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Phase classification: P1a ➔ P1 | Trial completion date: Dec 2023 ➔ Jun 2024

Phase classification • Trial completion date • Oncology • Solid Tumor

Prostaglandin E2 promotes Th17 differentiation induces corneal epithelial cell apoptosis and participates in the progression of dry eye. (PubMed, Arch Biochem Biophys) - "Scopolamine and dry environment were used to induce mice DE model. Celecoxib was used to inhibit PGE2...AH6809 and E7046 were used to pre-culture to inhibit EP2/4 in T cells to verify the effect of exogenous PGE2 on Th17 cell differentiation and corneal epithelial cell apoptosis...Blocking EP2/4 not only inhibited the proportion of Th17, but also alleviated the apoptosis of corneal epithelial cells caused by PGE2. PGE2 induces aggravation of inflammation by promoting the level of Th17 in the ocular surface, and causes corneal epithelial cell apoptosis, thereby participating in the progression of DE."

Journal • Dry Eye Disease • Inflammation • Ocular Inflammation • Ophthalmology • CD4 • IL17A

KEYNOTE 879: AN0025 and Pembrolizumab Combination in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=63 | Active, not recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • IO biomarker • Metastases • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

Discovery of Novel, Selective Prostaglandin EP4 Receptor Antagonists with Efficacy in Cancer Models. (PubMed, ACS Med Chem Lett) - "Due to favorable pharmacokinetics properties and good oral bioavailability (F = 76%), compound 36 was chosen for in vivo efficacy studies. Compound 36 inhibited tumor growth in a CT-26 colon cancer xenograft better than E7046 and a combination of 36 with capecitabine significantly suppressed tumor growth (TGI up to 94.26%) in mouse models."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Discovery of EP4 receptor antagonist KF-0210 for the treatment of cancers (AACR 2023) - "Oral administration of KF-0210 showed superior plasma exposure in rats and mice compared to E7046, another EP4 antagonist under clinical development. KF-0210 is a potent and selective EP4 antagonist with a good PK and safety profile. It shows the inhibitory effect on tumor growth in mouse models of colorectal and breast cancers. The combination treatment of KF-0210 and PD-1/PD-L1 antibodies shows a superior therapeutic effect compared to the monotherapy of each treatment."

Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TNFA

AN0025 and Pembrolizumab Combination in Advanced Solid Tumors (clinicaltrials.gov) - P1; N=84; Recruiting; Sponsor: Adlai Nortye Biopharma Co., Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • IO biomarker • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer • Urothelial Cancer

AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer. (PubMed, Radiother Oncol) - "Treatment with AN0025 administered for 10 weeks along with preoperative SCRT or LCRT did not appear to worsen the toxicity in subjects with locally advanced rectal cancer, was well-tolerated and showed promise in inducing both a pathological and complete clinical response. These findings suggest its activity deserves further investigation in larger clinical trials."

Combination therapy • Journal • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1a | N=63 | Recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Trial completion date: Nov 2022 ➔ Dec 2023 | Trial primary completion date: Sep 2022 ➔ Sep 2023

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • PIK3CA

KEYNOTE 879: AN0025 and Pembrolizumab Combination in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Trial completion date: Mar 2023 ➔ Nov 2025 | Trial primary completion date: Dec 2022 ➔ Apr 2025

Combination therapy • IO biomarker • Metastases • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

Phase 1 study of E7046, a PGE2 receptor EP-4 inhibitor that targets immunosuppressive myeloid cells in the tumor microenvironment (TME) (ESMO-IO 2017) - P1; "Conclusions Single-agent E7046 was tolerated with no MTD reached in heavily pretreated pts with myeloid-rich tumors. PD analysis of immune cell modulation to help determine the RP2D will be presented at the meeting."

Biomarker • Clinical • P1 data • Tumor microenvironment • Colorectal Cancer • Head and Neck Cancer • Pancreatic Cancer

Phase I study of E7046, a novel PGE2 receptor type 4 inhibitor, in patients with advanced solid tumors: Clinical results and effects on myeloid- and T-lymphoid cell-mediated immunosuppression. (ASCO-SITC 2018) - P1; "E7046 demonstrated favorable tolerability with preliminary evidence of anti-tumor activity and immune modulation in tumor and peripheral blood. MTD was not reached. Further studies of E7046 in combination with other agents are planned."

Clinical • P1 data • Solid Tumor

A Trial of AN0025 With Chemoradiation Therapy in Stage III NSCLC Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Rutgers, The State University of New Jersey | Initiation date: Jun 2022 ➔ Jan 2023

Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Reversing PD-1 Resistance in B16F10 Cells and Recovering Tumour Immunity Using a COX2 Inhibitor. (PubMed, Cancers (Basel)) - "Aspirin or celecoxib combined with pembrolizumab can effectively reverse tumour drug resistance. In addition, ptgs2 knockout or the use of the EP4 inhibitor E7046 abrogated drug resistance to anti-PD-1 treatment in B16F10-R tumour cells. Our study showed that inhibition of the COX2/PGE2/EP4 axis could increase the number of immune cells infiltrating the tumour microenvironment and recover drug-resistant tumour sensitivity to pembrolizumab. Thus, we highlight COX2 inhibition as a promising therapeutic target for drug-resistant tumours for future consideration."

IO biomarker • Journal • Oncology • Solid Tumor • PACERR • PD-1 • PTGS2