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782-F Pseudoprogression and subsequent shrinkage of refractory/relapsed pediatric solid tumors induced by GAIA-102: an interim report of the single-agent cohort in Phase I clinical trial
  1. Naonori Kawakubo1,
  2. Yui Harada1,
  3. Akihiko Tamaki2,
  4. Junnosuke Maniwa2,
  5. Yosuke Morodomi3,
  6. Yoshikazu Yonemitsu1,4 and
  7. Tatsuro Tajiri2
  1. 1Kyushu University, Fukuoka, Japan
  2. 2Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  3. 3Kyushu University Graduate School of Pharmaceutical Sciences, Fukuoka, Japan
  4. 4GAIA BioMedicine Inc., Fukuoka, Japan
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Pseudoprogression and subsequent shrinkage of solid tumor foci are typical clinical processes and are seen in approximately 2–8% of cases during immune checkpoint inhibitor (ICI) treatment. Refractory/relapsed pediatric solid tumors including neuroblastoma (NB), however, are well-known to be highly resistant to ICI. In addition, in the case of NB, specific patterns of killer cell immunoglobulin-like receptor (KIR) mismatch between recipient and donor at hematopoietic stem cell transplantation showed a significant impact on their survival. We recently developed a cell therapeutic agent showing a unique natural killer (NK) cell-like phenotype, GAIA-102. GAIA-102 is generated from mixed allogeneic peripheral blood mononuclear cells, which are derived from three or more healthy donors with specific combinations of HLA-C allele and KIRs, and demonstrates highly active accumulation and adhesion to tumor foci in vitro and in vivo. In addition, GAIA-102 could lead animals to complete cures in an established peritoneal dissemination mouse model in preclinical studies, suggesting that GAIA-102 could induce tumor-specific acquired immunity.

The aims of this Phase I clinical study are to assess the safety and proof of concept (POC) for the potential efficacy of GAIA-102, suggesting a treatment-mediated acquired immune response.

Methods GAIA-102 has been prepared as ‘off-the-shelf’ agents and stocked in vials under liquid nitrogen in a gas phase. The single-agent cohort of basket trial in this Phase I study is a typical 3+3 design with increased frequencies of intravenous infusion (5x106 cells/kg/dose), one to 3 times a week (LEVEL 1–3), and 3 patients would be added at the recommended frequencies. The primary endpoint is the safety of repeated intravenous injection of GAIA-102. Ten patients (6 for NB, 2 for osteosarcoma, 1 for each, hepatoblastoma and rhabdomyosarcoma) have been completed to evaluate dose-limiting toxicity (DLT) at the time of this abstract submission. The antitumor response as a secondary endpoint is evaluated by RECIST version 1.1.

Results The first-patient-in was on October 24, 2022. No DLT has been observed, and all four patients in LEVEL 3 exhibited mild to moderate fever. Typical pseudoprogression followed by subsequent shrinkage has been observed in some tumor foci of two NB patients (LEVEL 1 and 3). The target lesion of rhabdomyosarcoma also showed central necrosis (LEVEL 3).

Conclusions Pseudoprogression and subsequent tumor shrinkage were observed in NB (2 of 6 patients, 33.3%) by sole treatment of GAIA-102, suggesting the potential POC indicating that GAIA-102 may induce antitumor acquired immunity in a clinical setting.

Trial Registration ID: NCT05608148

Ethics Approval Approval No.2022306 (Institutional Review Board of Kyushu University Hospital)

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