Four of five complete responders in Rakuten Medical’s Phase 1b/2 combination study are still alive, some more than five years after treatment, in a disease where pembrolizumab monotherapy historically produced median overall survival around eight months. That gap frames why the long-term follow-up data from the ASP-1929-181 study, presented as an e-poster at ESMO 2026 in Madrid, drew attention despite the trial’s small size.

The updated analysis extended median follow-up from 31.7 months to 53.1 months across 17 efficacy-evaluable patients with recurrent or metastatic head and neck squamous cell carcinoma. Median overall survival reached 28.2 months, with roughly one in three patients (35.3%) still alive at four years. Among the five patients who achieved a complete response, four remained alive with follow-up ranging past 42 months and, in some cases, past 60 months. Median duration of response hit 44.3 months at the data cutoff, and four responders had not needed subsequent anticancer therapy after stopping study treatment. Exploratory subgroup cuts by HPV status, PD-L1 CPS expression, and tumor size showed broadly consistent results, and no new safety signals emerged.

The caveats matter. Nineteen patients enrolled; 17 were evaluable. Subgroup numbers are thin enough that consistency across them is suggestive, not definitive. Rakuten Medical acknowledges the limitations directly, framing the results as support for continued investigation rather than proof of benefit. The ongoing global Phase 3 ASP-1929-381 study (NCT06699212) is testing the combination as a first-line therapy for locoregionally recurrent HNSCC, a narrower population than the r/m setting studied here. That distinction in patient selection will shape whether the Phase 3 readout can reproduce anything close to what the Phase 1b/2 data showed.

The clinical question the Phase 3 must answer is whether photoimmunotherapy adds durable tumor control on top of what pembrolizumab and platinum-based regimens already deliver in the current first-line standard. Rakuten Medical is targeting a U.S. BLA submission in 2028 if the Phase 3 succeeds, making the trial’s enrollment pace and interim analysis timing the next concrete marker to watch.

Source link: https://www.prnewswire.com/news-releases/rakuten-medical-presents-long-term-follow-up-results-of-asp-1929-photoimmunotherapy-in-combination-with-pembrolizumab-for-rm-hnscc-at-esmo-2026-302917714.html

ASP-1929: the facts in one place

  • Also written: RM-1929, cetuximab sarotalocan
  • Sponsor: Rakuten Medical, Inc.
  • Mechanism: Antibody-dye conjugate targeting EGFR on cancer cells, activated by non-thermal red light (690 nm) to induce selective cell necrosis and immune activation
  • Indication studied: Locoregional recurrent head and neck squamous cell carcinoma (HNSCC); unresectable locally advanced or recurrent head and neck cancer
  • Phase: Global Phase 3
  • Enrollment: ASP-1929-381 (NCT06699212): ~400-412 patients; ASP-1929-301 (NCT03769506): 135 randomized patients
  • Primary endpoint: ASP-1929-381: Overall Survival; ASP-1929-301: PFS and OS
  • Headline result: Phase 1b/2 combination study (NCT04305795): median overall survival 25.6 months; 22.2% confirmed complete response rate; four of five complete responders still alive more than five years after treatment
  • Registry identifier: NCT06699212, NCT03769506, NCT04305795
  • Current status: Conditionally approved in Japan since September 2020; investigational outside Japan; BLA submission to U.S. FDA targeted as early as 2028
  • Conditional marketing approval in Japan: September 2020
  • NCT03769506 registered: December 2, 2018
  • Phase I Japanese study published in International Journal of Clinical Oncology: June 24, 2021
  • NCT06699212 initiated (Global Phase 3 + pembrolizumab announced): January 23, 2025
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Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.