Phase Ib/II study of ASP-1929 photoimmunotherapy (PIT) for esophageal cancer ineligible for curative standard therapies.

TPS474 Background: Esophageal squamous cell carcinoma (ESCC) remains a challenging malignancy, particularly for patients who are ineligible for curative surgery, chemoradiotherapy (CRT), or endoscopic treatment. Photoimmunotherapy (PIT) with ASP-1929 (cetuximab conjugated to IRDye 700DX) and 690-nm red light offers tumor-selective cytotoxicity. ASP-1929 PIT has shown promising efficacy, with a manageable safety profile in phase I/II studies in recurrent head and neck squamous cell carcinoma. However, its application in ESCC is limited due to anatomical and technical considerations. This trial explores endoscopic ASP-1929 PIT potential in ESCC. Methods: This is an open-label, single-arm, investigator-initiated phase Ib/II trial evaluating the safety and efficacy of ASP-1929 PIT in patients with ESCC who are not eligible for standard curative therapies. Eligible patients are ≥20 years with histologically confirmed ESCC (T2 or shallower) and no lymph node or distant metastasis. Key inclusion criteria include residual/recurrent lesions after CRT or RT (including cases refractory to or ineligible for Photodynamic Therapy) or patients medically unfit for surgery/CRT. ASP-1929 is administered intravenously on Day 1, followed by endoscopic laser illumination with 690-nm red light 24 hours later on Day 2, with additional illumination on Day 3 if needed. Up to four treatments cycles are permitted, with an interval of at least 28 days. Phase Ib determines the recommended dose of laser energy using a 3+3 dose-escalation design with either cylindrical or side-firing diffuser devices. Phase II then evaluates efficacy and safety at the recommended dose. Primary endpoints of phase Ib and II are dose-limiting toxicity and centrally assessed L-CR (Local-Complete Response) rate, respectively. Secondary endpoints include investigator-assessed L-CR rate, progression-free survival, local PFS, overall survival, device malfunctions, pharmacokinetics, anti-drug antibody formation, and safety. Planned sample size of part phase II is 28 patients, providing power of 90% with threshold and expected centrally assessed L-CR rate of 5% and 30%, and one-sided alpha of 2.5%. Trial number of this study is jRCT2080224666 (https://jrct.mhlw.go.jp/latest-detail/jRCT2080224666). This study was approved by the IRB on December 2018 and enrollment began in August 2019. As of August 2025, phase Ib is ongoing at one site in Japan with a total number of 12 patients treated. Clinical trial information: jRCT2080224666 .