1040P - Phase I study of IL-8 inhibitor AMY109 plus atezolizumab (atezo) in patients (pts) with advanced solid tumours

Background

AMY109 is a humanised monoclonal antibody that binds to IL-8. IL-8 plays a role in immunosuppression, fibrosis and epithelial-to-mesenchymal transition in the tumour microenvironment (TME). Combining AMY109 with atezo (anti-PD-L1) may enhance its anti-tumour effects by making the TME more favourable to PD-L1 inhibition.

Methods

This multicentre, open-label, dose-escalation study evaluated the safety, tolerability and pharmacokinetics (PK) of AMY109 (2–45 mg/kg) plus atezo (1200 mg) IV q3w in Part 1, and AMY109 (15–45 mg/kg) plus atezo (1200 mg) IV q3w in Part 2 in pts with previously treated advanced solid tumours and ECOG PS 0–1. Primary endpoints were AMY109 and atezo PK, safety and dose-limiting toxicity (DLT) in Part 1, and safety and anti-tumour activity in Part 2.

Results

Thirty-eight pts (18 in Part 1, 20 in Part 2) were enrolled (Table). Part 1 showed no DLTs and a dose-proportional increase in AMY109 exposure over 2–45 mg/kg, with no apparent change in mean atezo serum concentrations (94–115 μg/mL at Cycle 2 pre-dose across AMY109 dose groups). In Part 2, a total of 4, 12 and 4 pts received 15, 30 and 45 mg/kg AMY109, respectively. Accumulation of plasma IL-8 concentration after starting AMY109 was seen in all dose cohorts. The table shows safety data and anti-tumour activity. No adverse events led to treatment withdrawal. Overall, the objective response rate was 5%; the disease control rate was 29%. The two pts with partial responses had uterocervical and pancreatic cancer, respectively, and had been treated for >500 days at the cut-off date (22 July 2022): one received 45 mg/kg AMY109 throughout, and the other received 30 mg/kg AMY109 until cycle 6, and 45 mg/kg thereafter. Exploratory biomarker results will be presented.

Table: 1040P

TRAE, treatment-related adverse event (related to any treatment). ^aPatients had oesophageal, colorectal, head and neck, pancreatic, breast, uterine, ovarian and other cancers.

Conclusions

AMY109 showed dose-proportional increases in exposure. With no DLTs, AMY109 plus atezo was well tolerated in pts with advanced solid tumours, with no new safety signals. The partial responses were durable.

Clinical trial identification

jRCT2080225101.

Editorial acknowledgement

Research support for third-party writing assistance for this abstract, furnished by Samantha Santangelo, PhD, of Health Interactions, was provided by Chugai Pharmaceuticals, Ltd.

Legal entity responsible for the study

Chugai Pharmaceuticals, Ltd.

Funding

Chugai Pharmaceuticals, Ltd.

Disclosure

Y. Kuboki: Financial Interests, Institutional, Other, Medical writing support: Chugai; Financial Interests, Institutional, Research Grant: Taiho, Astelas, Lilly, Takeda, Daiichi Sankyo, AstraZeneca, Boehringer Ingelheim, Chugai, Genmab, Incyte, Abbie, Amgen, Merck; Financial Interests, Personal, Other, Consulting Fees: Incyte, Takeda, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Speaker’s Bureau: Taiho, Lilly, Takeda; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.. S. Kitano: Financial Interests, Personal and Institutional, Other, Lecture fee: Chugai, AstraZeneca, Pfizer, Boehringer Ingelheim, MSD, Eisai, Ono Pharmaceutical Co., Ltd., GSK, Daiichi Sankyo, Takeda, Eli Lilly Japan K.K.; Financial Interests, Personal, Other, Lecture fee: Taiho, Novartis, Bristol Myers Squibb, Merck KGaA, Novartis, Janssen; Financial Interests, Personal, Advisory Board: Novartis, Sumitomo Pharma, Bristol Myers Squibb, Rakuten Medical; Financial Interests, Institutional, Research Grant: Astellas, Incyte, AbbVie, Loxo Oncology, JSPS(Japan Society for the Promotion of Science), AMED (Japan Agency for Medical Research and Development); Financial Interests, Personal and Institutional, Research Grant: Chugai, AstraZeneca, Pfizer, Boehringer Ingelheim, MSD, Eisai, Ono Pharmaceutical Co., Ltd., GSK, Daiichi Sankyo, Takeda, Eli Lilly Japan K.K.; Financial Interests, Personal and Institutional, Advisory Board: Chugai, AstraZeneca, Pfizer, Boehringer Ingelheim, MSD, Eisai, Ono Pharmaceutical Co., Ltd., GSK; Financial Interests, Research Grant: Takara Bio Inc.; Financial Interests, Personal, Advisory Role: ImmuniT Research Inc., United Immunity; Financial Interests, Personal, Other, Comment fee: PMDA(Pharmaceuticals and Medical Devices Agency); Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.. M. Ikeda: Financial Interests, Institutional, Other, Research: Chugai ; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.. T. Koyama: Financial Interests, Personal and Institutional, Research Grant: Chugai ; Financial Interests, Personal and Institutional, Principal Investigator: Chugai; Financial Interests, Personal and Institutional, Speaker’s Bureau: Chugai; Financial Interests, Personal, Speaker’s Bureau: Sysmex; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Novartis, Lilly, Takeda, Zymworks; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Novartis, Lilly, Takeda, Zymworks; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.. H. Mizugaki: Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co., Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.. T. Narikiyo, Y. Yamaguchi, T. Ishida, R. Takubo, C. Ogami: Financial Interests, Personal, Full or part-time Employment: Chugai Pharmaceutical Co., Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.. M. Sekiya, Y. Nakagawa: Financial Interests, Personal, Full or part-time Employment: Chugai Pharmaceutical Co., Ltd.; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.. N. Yamamoto: Financial Interests, Institutional, Principal Investigator, Research funding: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, Cmic, Rakuten Medical; Financial Interests, Personal, Advisory Board: Eisai, Takeda, Boehringer Ingelgeim, Cmic, Chugai, Merck, Healios; Financial Interests, Personal, Speaker’s Bureau: ONO, Chugai, Daiichi Sankyo, Eisai; Non-Financial Interests, Personal, Funding, Research funding: Support for third-party writing assistance: Chugai Pharmaceutical Co., Ltd.