Abstract CT193: Phase 1 clinical trial evaluating the safety, tolerability, and immunogenicity of AST-021p, a novel cancer vaccine targeting HSP90-derived epitopes in advanced solid tumor patients (CornerStone-002)
Authors: Kang Eun Joo , Lee Kyoungmin , Kim In Ho , Kim Ju Won , Kim Jwa Hoon , Lee Soohyeon , Lee Jiwon , Shin Kabsoo , Park Sejun , Kim Joori , Shin Hyun Won , Park Kyong Hwa 
Published: April 2024

Abstract
Background: AST-021p is an "off-the-shelf" therapeutic cancer vaccine composed of two peptides, AST-021p4 and AST-021p5, derived from MHC class II-specific epitopes of Hunam HSP90 protein. Both peptides serve as antigenic determinants for HSP90 and act as a tumor-associated antigen (TAA) inducing activation of type 1 helper T cells (Th1). Th1 cell immunologically elicited by AST-021p secrete cytokines, including IFN-γ, and activate local antigen presenting cells (APC) enhancing cross priming at the tumor site. This immunological activity, through the mechanism of cross priming, sequentially leads to the activation of cytotoxic T cells and epitope spreading. In preclinical studies using the MMTV neu gene overexpressing mouse model, the administration of the HSP90 peptide vaccine, AST-021p, significantly inhibited tumor growth. Based on these scientific rationales, The first-in-human (FIH) study was conducted to evaluate the safety, tolerability, and immunogenicity of AST-021p in advanced solid tumor patients have no treatment option.
Methods: Phase 1 study (CornerStone-002, NCT No.: 04864418) was conducted on patients with recurrent or metastatic solid tumors for whom applicable standard treatment options were unavailable (patient enrollment period: June 9, 2021, to June 14, 2023). Four-dose cohorts of AST-021p (Cohort 1: 1.2mg, Cohort 2: 2.4mg, Cohort 3: 3.6mg, Cohort 4: 4.8mg) received three vaccinations at 2-week intervals (Priming immunization) followed by boosting immunization with 4-week interval based on PI's discretion. Enrolling one patient initially in the lowest dose cohort, Cohort 1 (1.2mg), dose escalation occurred sequentially after confirming safety and tolerability. Subsequently, each dose cohort (Cohort 2: 2.4mg, Cohort 3: 3.6mg, Cohort 4: 4.8mg) enrolled six patients each for vaccination. Antigen-specific immune response was assessed by IFNγ ELISPOT using PBMCs from the subjects at baseline, 4 weeks, and 8 weeks.
Results: During the study period, a total of 22 patients were enrolled (Cohort 1: 1, Cohort 2: 6, Cohort 3: 8, Cohort 4: 7). The median age of the patients was 66, with a gender distribution of 14 males and 8 females. Among the 22 patients, 20 completed the priming immunization with 3 vaccinations, and 7 of them proceeded with the boosting immunization. A total of 75 adverse events were reported in 21 patients (95.5%). Adverse drug reactions (ADRs) occurred in 15 patients (68.2%), accounting for 92 cases. The most common ADR was injection site reaction (ISR), observed in 15 patients (68.2%), with 35 cases and all reactions were graded as 1 or 2. Serious adverse events (SAEs), including gastrointestinal hemorrhage, vomiting, and aspiration, were observed in 3 patients (13.6%), totaling 3 cases. However, these events were unrelated to AST-021p.
Conclusions: This study, as the first-in-human (FIH) administration of the AST-021p, demonstrated safety and tolerability across all four dose groups. Plus, optimal immunogenic dose (OID) and recommended phase 2 dose (RP2D) were confirmed based on AST-021p-specific immunogenicity and safety.
Citation Format: Eun Joo Kang, Kyoungmin Lee, In Ho Kim, Ju Won Kim, Jwa Hoon Kim, Soohyeon Lee, Jiwon Lee, Kabsoo Shin, Sejun Park, Joori Kim, Hyun Won Shin, Kyong Hwa Park. Phase 1 clinical trial evaluating the safety, tolerability, and immunogenicity of AST-021p, a novel cancer vaccine targeting HSP90-derived epitopes in advanced solid tumor patients (CornerStone-002) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT193.