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Clinical Trial
. 2021 Jul 1;27(13):3649-3660.
doi: 10.1158/1078-0432.CCR-20-3742. Epub 2021 Apr 20.

Clinical and Immunologic Responses to a B-Cell Epitope Vaccine in Patients with HER2/neu-Overexpressing Advanced Gastric Cancer-Results from Phase Ib Trial IMU.ACS.001

Ursula Wiedermann  1 , Erika Garner-Spitzer  2 , Yee Chao  3 , Marina Maglakelidze  4 , Iurie Bulat  5 , Arunee Dechaphunkul  6 , Wichit Arpornwirat  7 , Chaiyut Charoentum  8 , Chia-Jui Yen  9 , Thomas Cheung Yau  10 , Suebpong Tanasanvimon  11 , Jedzada Maneechavakajorn  12 , Aumkhae Sookprasert  13 , Li-Yuan Bai  14 , Wen-Chi Chou  15 , Teerapat Ungtrakul  16 , Mirjana Drinic  2 , Joshua Tobias  2 , Christoph C Zielinski  17 , Leslie Chong  18 , Nicholas J Ede  18 , Mark T Marino  18 , Anthony J Good  18
Affiliations
Clinical Trial

Clinical and Immunologic Responses to a B-Cell Epitope Vaccine in Patients with HER2/neu-Overexpressing Advanced Gastric Cancer-Results from Phase Ib Trial IMU.ACS.001

Ursula Wiedermann et al. Clin Cancer Res. .

Abstract

Purpose: HER2/neu is overexpressed in up to 30% of gastroesophageal adenocarcinomas (GEA) and linked to poor prognosis. Recombinant mAbs to treat HER2/neu-overexpressing cancers are effective with limitations, including resistance and toxicity. Therefore, we developed a therapeutic B-cell epitope vaccine (IMU-131/HER-Vaxx) consisting of three fused B-cell epitopes from the HER2/neu extracellular domain coupled to CRM197 and adjuvanted with Montanide. This phase Ib study aimed to evaluate the optimal/safe dose leading to immunogenicity and clinical responses (https//clinicaltrials.gov/ct2/show/NCT02795988).

Patients and methods: A total of 14 patients with HER2/neu-overexpressing GEA were enrolled, and dose escalation (10, 30, 50 μg) was performed in three cohorts (C). Immunogenicity was evaluated by HER2-specific Abs and cellular responses, clinical responses by CT scans according to RECIST version 1.1.

Results: IMU-131 was safe without vaccine-related significant local/systemic reactions or serious adverse events. A total of 11 of 14 patients were evaluable for changes in tumor size and vaccine-specific immune responses. One patient showed complete, 5 partial responses, and 4 stable diseases as their best response. HER2-specific IgG levels were dose dependent. In contrast to patients in C1 and C2, all patients in C3 mounted substantial HER2-specific Ab levels. In addition, cellular vaccine responses, such as Th1-biased cytokine ratios and reduced regulatory T cell numbers, were generated. Progression-free survival was prolonged in C3, correlating with the vaccine-specific humoral and cellular responses.

Conclusions: IMU-131 was well tolerated and safe. The induced HER2-specific Abs and cellular responses were dose dependent and correlated with clinical responses. The highest dose (50 μg) was recommended for further evaluation in a phase II trial, with chemotherapy + IMU-131 or chemotherapy alone, which is currently ongoing.

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