Akalux (cetuximab sarotalocan) / Rakuten Medical, Orient Europharma - LARVOL DELTA

Long-Term Results of ASP-1929 Photoimmunotherapy (PIT) With Pembrolizumab (PEM) in Patients with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (ESMO 2026) - No abstract available

Clinical • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Photoimmunotherapy With ASP-1929 and Cemiplimab for the Treatment of Refractory, Inoperable, and Metastatic Stage IIIB-IV Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Roswell Park Cancer Institute | N=27 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • ROS1

Safety and Efficacy Findings From a Phase Ib/II Study of ASP-1929 Photoimmunotherapy With Pembrolizumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. (PubMed, Head Neck) - "ASP-1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC."

Journal • P1/2 data • Gastrointestinal Disorder • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Epidermal growth factor receptor-targeted near-infrared photoimmunotherapy for epidermal growth factor receptor-expressing advanced solid tumors: a scoping review of barriers and enablers to clinical translation. (PubMed, Antib Ther) - "This review focuses specifically on the IR700 (IRDye700DX)-based conjugate cetuximab sarotalocan (RM-1929/ASP-1929), which is the only NIR-PIT construct to have advanced into clinical use, while acknowledging the broader and rapidly expanding photoimmunotherapy landscape. Broader adoption is constrained by biological, technical, regulatory and system-level barriers, as well as gaps in comparative effectiveness, long-term outcomes, and health-economic evidence. Addressing these challenges through targeted clinical trials, improved patient selection, and implementation-focused research will be essential to advance NIR-PIT toward wider clinical integration."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

Adverse events of cetuximab sarotalocan in photoimmunotherapy: insights from the Japanese adverse drug event report database. (PubMed, Cancer Chemother Pharmacol) - "The described safety profile of cetuximab sarotalocan in photoimmunotherapy offers insights for its proper use as well as baseline data for the development and improvement of cancer photoimmunotherapy."

Adverse events • Journal • Retrospective data • Gastrointestinal Disorder • Head and Neck Cancer • Oncology • Solid Tumor

EGFR Targeted Photoimmunotherapy With ASP-1929 for Locally Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: Brown University

New P1/2 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Development of Intra arterial Photoimmunotherapy for Recurrent or Metastatic Head and Neck Cancer (AHNS 2026) - "A catheter was inserted via the superficial temporal artery into the tumor-feeding artery, and IA Nivolumab (20 mg × 2 doses) was administered...Development of Intra-arterial Photoimmunotherapy (PIT) The current approved protocol for Cetuximab Sarotalocan Sodium (Akalux®) requires an IV infusion of 640 mg/m² over 24 hours, followed by laser irradiation under general anesthesia the next day. Refined protocol involves IA administration of Akalux® at 1/100 to 1/10 of the standard dose, followed immediately laser irradiation under local anesthesia, with subsequent outpatient IV Pembrolizumab seven days later...Through the analysis of "Immune Signatures" in tumor tissues before and after IA administration in the same patient, we expect to identify true predictive factors for therapeutic efficacy. Furthermore, this project is expected to contribute to academia-industry collaboration, new pharmaceuticals tailored for IA therapy and the advancement..."

First-in-human • Metastases • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • CD8

Investigation of treatment procedure to optimize photoimmunotherapy for head and neck cancer (AHNS 2026) - "Introduction: Photoimmunotherapy (PIT), using cetuximab sarotalocan sodium and 690 nm laser light, is a treatment for unresectable locally advanced or recurrent head and neck cancer. It is important to illuminate the entire lesion to maximize the efficacy of PIT. Close monitoring and appropriate procedures are required because TRAESI may occur despite adequate pre-treatment risk assessment."

Head and Neck Cancer • Oncology • Solid Tumor

Efficacy and potential of frontal diffuser illumination in head and neck photoimmunotherapy (AHNS 2026) - "Background: Photoimmunotherapy (PIT) using cetuximab sarotalocan sodium (Akalux®) has rapidly expanded in Japan, with more than 1100 cases performed nationwide since its clinical introduction. Our data suggest that frontal illumination in photoimmunotherapy can achieve CR even in moderately thick lesions, potentially expanding its indications. Accumulation of further clinical experience and prospective validation are warranted to establish evidence-based criteria for selecting optimal illumination approaches according to tumor site, depth, and morphology."

Clinical • Head and Neck Cancer • Hypopharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Utility of a Simplified Irradiator for Photosensitivity Testing in Head and Neck Photoimmunotherapy. (PubMed, In Vivo) - "The simplified irradiator allows standardized, weather-independent photosensitivity testing after HN-PIT, although further studies are needed to confirm sensitivity and long-term reliability."

Journal • Dermatology • Head and Neck Cancer • Oncology • Solid Tumor

Clinical fluorescent contrast agents for image-guided surgery. (PubMed, Fundam Res) - "This review provides a comprehensive overview of seven FDA-approved intraoperative fluorescence contrast agents-Indocyanine Green (ICG), Fluorescein Sodium, 5-Aminolevulinic Acid (5-ALA), Methylene Blue (MB), Cysview (Hexaminolevulinate), Cytalux (OTL38), and Akalux-highlighting their molecular characteristics, approved indications, and clinical performance. Finally, we discuss key considerations for selecting appropriate agents in clinical practice, including tissue specificity, administration route, imaging depth, and regulatory status. Looking forward, the continued integration of molecular diagnostics and imaging is expected to enable more accurate, individualized surgical interventions and support the future development of theranostic strategies."

Journal • Review • Oncology

Rakuten Medical is accelerating its global Phase 3 clinical trial (ASP-1929-381, NCT06699212) to support its top priority of submitting a Biologics License Application (BLA) to the U.S. FDA in 2028 (PRNewswire) - "The ASP-1929-381 trial evaluates ASP-1929 photoimmunotherapy in combination with pembrolizumab as a first-line treatment for recurrent head and neck cancer. Patient enrollment is progressing ahead of plan, across the United States, Taiwan, Japan, and Ukraine."

FDA filing • Trial status • Squamous Cell Carcinoma of Head and Neck

A phase 3, randomized, double-arm, open-label, controlled study of ASP-1929 photoimmunotherapy (PIT) versus physician's choice standard of care (SOC) for patients with locoregional, recurrent head and neck squamous cell carcinoma (HNSCC). (ASCO 2026) - P3 | "In the control arm, patients received the physician's choice of standard of care (docetaxel, cetuximab, methotrexate, or paclitaxel) until disease progression, intolerable adverse effects, or discontinuation of study treatment. Considering the limitations of the study data, these results support ASP-1929 PIT as a tolerable and clinically active treatment option for locoregional, recurrent HNSCC and its ongoing evaluation in the current randomized global Phase 3 ASP-1929-381 study."

Clinical • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Feasibility study of photoimmunotherapy combination with ASP-1929 for vulvar, vaginal, and cervical cancer. (PubMed, J Gynecol Oncol) - "We demonstrated correlation between cetuximab-binding and IHC staining intensity, establishing IHC criteria (≥2+) for patient selection. EGFR positivity (71.4%-87.5%) indicates substantial eligibility for ASP-1929 PIT. Therapeutic efficacy will be evaluated in the HICARi study."

IO biomarker • Journal • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Squamous Cell Carcinoma

Hokkaido phase II study of photo-immunotherapy combination with ASP-1929 for recurrent or persistent EGFR-positive vulvar, vaginal, and cervical cancers not amenable to further radiotherapy (HICARi study). (PubMed, J Gynecol Oncol) - "Sixteen patients were enrolled, with the first 4 forming a safety cohort. Japan Registry of Clinical Trials Identifier: jRCT2011240034."

IO biomarker • Journal • P2 data • Cervical Cancer • Gynecologic Cancers • Head and Neck Cancer • Oncology • Solid Tumor • Vaginal Cancer • Vulvar Cancer • EGFR

Complete response of unresectable maxillary undifferentiated pleomorphic sarcoma with Alluminox photoimmunotherapy. (PubMed, BMJ Case Rep) - "After a partial response to definitive chemoradiotherapy, she underwent two sessions of Alluminox photoimmunotherapy with Akalux (cetuximab-sarotalocan sodium) activated by near-infrared illumination via transoral and transnasal optical diffusers under intraoperative navigation and cone-beam CT. This technique enables selective tumour ablation, induces immunogenic cell death and offers potential synergy with immune checkpoint inhibitors. She achieved complete radiological and pathological remission with minimal toxicity and remains disease-free with preserved oral function at 8 months."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • EGFR

EGFR-targeted photoimmunotherapy and its association with the immune microenvironment in locoregional recurrent head and neck squamous cell carcinoma. (PubMed, Front Immunol) - "Epidermal growth factor receptor (EGFR)-targeted photoimmunotherapy using cetuximab sarotalocan sodium (RM-1929) represents a novel therapeutic modality that induces selective tumor cell death and may influence the tumor immune microenvironment (TIME) in head and neck squamous cell carcinoma (HNSCC). Distinct TIME characteristics and potential immune remodeling, involving CD39+CD8+ T cell, were observed. These observations provide a rationale for further investigation of photoimmunotherapy as a strategy to integrate local tumor ablation with systemic immune modulation in recurrent HNSCC."

IO biomarker • Journal • Retrospective data • Head and Neck Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • EGFR • ENTPD1 • PD-L1

ASP-1929-381: Study of the combination of the drug ASP-1929 and light illumination with the device PIT690 laser system in addition with pembrolizumab versus Standard of Care in the treatment of locoregional recurrent squamous cell carcinoma of the head and neck with no distant metastases (clinicaltrialsregister.eu) - P2/3 | N=30 | Not yet recruiting | Sponsor: Rakuten Medical Inc.

New P2/3 trial • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

ECLIPSE: A Study of ASP-1929 Photoimmunotherapy in Combination With Pembrolizumab in First-line Treatment of Locoregional Recurrent Squamous Cell Carcinoma of the Head and Neck With No Distant Metastases (clinicaltrials.gov) - P3 | N=412 | Recruiting | Sponsor: Rakuten Medical, Inc.

New P3 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

COX-2/PGE2 driven, photoimmunotherapy-induced edema is reduced by prophylactic NSAIDs in mouse tumor models (AACR 2026) - "In conclusion, this is the first report showing increased COX-2/PGE2 post-PIT, linking PGE2 secretion with edema generation, and suggests COX-2 inhibition to combat ASP-1929 PIT-induced edema for improved patient safety. The translation of this result to the clinical setting is under investigation at treatment centers throughout Japan (jRCTs031250140)."

IO biomarker • Preclinical • Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Solid Tumor • PTGS2

Reduction in photoimmunotherapy-induced edema with COX-2 inhibition: Combatting clinically relevant adverse events without compromising efficacy (AACR 2024) - "ASP-1929 photoimmunotherapy (PIT), an investigational drug-device combination, consists of an epithelial growth factor receptor (EGFR)-targeting drug, cetuximab, conjugated to a light-activatable dye, IRDye® 700DX, and a laser light. Importantly, we found the reduction in edema with meloxicam was not associated with a loss of therapeutic benefit based on measurement of tumor growth. In conclusion, the use of COX-2 inhibitors may be directly translated to the clinic for the benefit of patients receiving ASP-1929 PIT and should undergo further evaluation."

Adverse events • Clinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • EPHA2 • IL10 • IL6

Pathological features of residual head and neck cancer after near-infrared photoimmunotherapy: implications of an unfavorable tumor immune microenvironment. (PubMed, Photodiagnosis Photodyn Ther) - "Residual tumors after near-infrared photoimmunotherapy can occur despite adequate laser irradiation and epidermal growth factor receptor expression. Our observations imply that insufficient immune activation within the tumor microenvironment may contribute to treatment resistance. Further characterization of the post-photoimmunotherapy tumor microenvironment will be essential to better understand treatment mechanisms and to optimize therapeutic efficacy."

IO biomarker • Journal • Fibrosis • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • EGFR • FOXP3 • PD-1

Outcomes of Near-Infrared Photoimmunotherapy for Head and Neck Cancer: A Single-Center Retrospective Study. (PubMed, Cancers (Basel)) - "NIR-PIT was independently associated with improved OS in patients with unresectable recurrent or metastatic head and neck cancer without distant metastasis. Prospective multicenter studies are warranted to validate these findings."

Journal • Retrospective data • Head and Neck Cancer • Oncology • Solid Tumor

Phase Ib/II study of ASP-1929 photoimmunotherapy (PIT) for esophageal cancer ineligible for curative standard therapies. (ASCO-GI 2026) - P | "Photoimmunotherapy (PIT) with ASP-1929 (cetuximab conjugated to IRDye 700DX) and 690-nm red light offers tumor-selective cytotoxicity. 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."

P1/2 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology

Rakuten Medical Raises $100 Million in Oversubscribed Series F to Accelerate Development Toward U.S. Regulatory Approval (PRNewswire) - "Rakuten Medical will utilize the Series F proceeds to advance its top priority: securing U.S. regulatory approval for ASP-1929, Rakuten Medical's designation for its first investigational photoimmunotherapy drug. The company is currently enrolling patients into its global Phase 3 trial (ASP-1929-381, NCT06699212), evaluating ASP-1929 photoimmunotherapy in combination with pembrolizumab as a first-line therapy for recurrent head and neck cancer. The proceeds will allow Rakuten Medical to strengthen its operational capabilities to accelerate enrollment in the U.S., Taiwan, Japan, Ukraine and Poland. Based on trial results, Rakuten Medical aims to submit a Biologics License Application (BLA) to the U.S. FDA in 2028."

FDA filing • Financing • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck