Akalux (cetuximab sarotalocan) / Rakuten Medical - LARVOL DELTA

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=27 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase 3 randomized study of ASP-1929 photoimmunotherapy in combination with pembrolizumab versus standard of care in locoregional recurrent head and neck squamous cell carcinoma (HNSCC). (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT06699212 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

Efficacy, safety, and immune biomarkers in RM-1929 photoimmunotherapy for locoregional, recurrent head and neck squamous cell carcinoma (COSM 2025) - "The treatment utilized cetuximab sarotalocan sodium, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody conjugated with the photoabsorber IR700...In 12 out of 18 cases, pembrolizumab monotherapy or nivolumab was administered an average of 58 days post-treatment... RM-1929 photoimmunotherapy demonstrated favorable local control with manageable adverse events. Ongoing research aims to identify predictive and immune biomarkers to further optimize this therapy."

Biomarker • Clinical • IO biomarker • CNS Disorders • Head and Neck Cancer • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Efficacy, safety, and immune biomarkers in RM-1929 photoimmunotherapy for locoregional, recurrent head and neck squamous cell carcinoma (AHNS-COSM 2025) - "The treatment utilized cetuximab sarotalocan sodium, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody conjugated with the photoabsorber IR700...In 12 out of 18 cases, pembrolizumab monotherapy or nivolumab was administered an average of 58 days post-treatment... RM-1929 photoimmunotherapy demonstrated favorable local control with manageable adverse events. Ongoing research aims to identify predictive and immune biomarkers to further optimize this therapy."

Biomarker • Clinical • IO biomarker • CNS Disorders • Head and Neck Cancer • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination with Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=23 | Active, not recruiting | Sponsor: Rakuten Medical, Inc. | N=74 ➔ 23 | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jun 2024 ➔ Jun 2026

Enrollment change • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Photoimmunotherapy for head and neck cancer: A systematic review. (PubMed, Auris Nasus Larynx) - "Photoimmunotherapy is a new cancer treatment that uses cetuximab sarotalocan sodium, a conjugate of cetuximab and the light activatable dye, IR700, and red light at a wavelength of 690 nm. Photoimmunotherapy is an important technology for the future of various cancer treatments, and it is essential to strive for the development and widespread use of photoimmunotherapy in clinical practice. In this review, we will explain the mechanism of photoimmunotherapy, treatment cases, clinical trial data, reports from real world data in Japan, and future issues and prospects as seen in actual clinical practice."

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

Rakuten Medical Announces Initiation of Global Phase 3 Trial of ASP-1929 Photoimmunotherapy in Combination with Pembrolizumab for First-Line Recurrent Head and Neck Cancer (PRNewswire) - "Rakuten Medical...announced the initiation of its global multi-regional Phase 3 clinical trial evaluating ASP-1929 photoimmunotherapy in combination with anti-PD-1 (pembrolizumab) as a first-line therapy for recurrent head and neck squamous cell carcinoma (HNSCC)....The first patient in this trial recently received a study treatment at the Avera Cancer Institute in Sioux Falls, South Dakota, USA. Alongside the U.S., patient enrollment is slated for sites in Japan and Taiwan, followed by additional countries and regions....Approximately 400 patients globally will be randomized to either an experimental arm receiving ASP-1929 photoimmunotherapy in combination with pembrolizumab, or a control arm receiving the current pembrolizumab-based standard of care (SOC)..."

Trial status • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

ASP-1929-301: ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy (clinicaltrials.gov) - P3 | N=135 | Active, not recruiting | Sponsor: Rakuten Medical, Inc. | N=275 ➔ 135 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • 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=408 | Recruiting | Sponsor: Rakuten Medical, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • 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=408 | Not yet recruiting | Sponsor: Rakuten Medical, Inc.

Combination therapy • New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/Neck Cancer for Patients Who Have Failed At Least Two Lines of Therapy (clinicaltrials.gov) - P3 | N=275 | Recruiting | Sponsor: Rakuten Medical, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Sep 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Rakuten Medical Announces New Management Team to Drive the Next Phase of Growth and Innovation (PRNewswire) - "The new management team is set to further advance Rakuten Medical's Alluminox platform and prioritize obtaining FDA approval for ASP-1929 as early as possible. The company's new global Phase 3 study of ASP-1929 photoimmunotherapy in combination with anti-PD-1 for first-line recurrent head and neck squamous cell carcinoma (HNSCC) is expected to commence first in the United States in 2H 2024."

New P3 trial • Squamous Cell Carcinoma of Head and Neck

ASP-1929 Photoimmunotherapy (PIT) Study in Patients With Recurrent Head/Neck Cancer (clinicaltrials.gov) - P2 | N=9 | Active, not recruiting | Sponsor: Rakuten Medical, Inc. | Recruiting ➔ Active, not recruiting | N=22 ➔ 9 | Trial completion date: Mar 2027 ➔ Jun 2026 | Trial primary completion date: Mar 2025 ➔ Jul 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Recent strides in macromolecular targeted photodynamic therapy for cancer. (PubMed, Curr Opin Chem Biol) - "The recent approval of Akalux® for antibody-targeted photodynamic therapy (PDT) in Japan (also known as photoimmunotherapy), and the recent approval of Cytalux® for folate-specific image guided surgery by the FDA have motivated the continued development of macromolecular targeted PDT for cancer management. This review spotlights some of the most recent advances in macromolecular targeted PDT since 2021, exploring the latest advances in protein engineering, adaptive macromolecular constructs and nanotechnology, adoption of immune checkpoint inhibitors, and targeting using biomimetic membranes. These strategies summarized here attempt to expand the functionality, benefit, and success of macromolecular targeting for PDT to advance the technology beyond what has already entered into the clinical realm."

Journal • Review • Oncology

Recent safety and efficacy findings from a phase 1b/2 open-label combination study of ASP-1929 photoimmunotherapy with anti-PD-1 therapy in EGFR-expressing advanced head and neck squamous cell carcinoma (HNSCC). (ASCO 2024) - P1/2 | "ASP-1929 photoimmunotherapy (PIT) combines EGFR-targeting cetuximab, with a light-activatable dye, IRDye 700DX, and a laser light for localized drug activation... A phase 1b/2 open-label study of pts with recurrent locally advanced (rLA) and/or metastatic (m) HNSCC evaluating the safety and efficacy of ASP-1929 PIT in combination with anti-PD-1 (pembrolizumab) therapy (NCT04305795)... ASP-1929 PIT in combination with anti-PD-1 therapy was generally well tolerated. Initial data demonstrate promising overall survival and response rates with this combination therapy in pts with rLA and/or m HNSCC lacking LR treatment options."

Clinical • Metastases • P1/2 data • Gastrointestinal Disorder • Head and Neck Cancer • Hematological Disorders • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Photoimmunotherapy in nasopharyngeal carcinoma recurrence. (ASCO 2024) - "Photoimmunotherapy uses an antibody-drug conjugate, cetuximab sarotalocan sodium, comprising cetuximab, a chimeric monoclonal antibody (IgG1) that targets human EGFR, and a light-sensitive dye, IRDye 700DX (IR700). The outcomes of the photoimmunotherapy demonstrated successful local control of recurrent nasopharyngeal carcinoma. This innovative therapeutic approach holds significant potential for addressing nasopharyngeal cancer recurrence. However, it is crucial to carefully evaluate patients who can safely be treated using this method."

Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

Rakuten Medical to Host R&D Day Highlighting Recent Interim Data from Phase 1b/2 Clinical Trial of ASP-1929 Photoimmunotherapy in Combination with anti-PD-1 in r/m HNSCC (PRNewswire) - "Rakuten Medical, Inc...announced that it will host a virtual R&D Day on Thursday, June 20, 2024 at 1:00 pm ET / 10:00 am PT. The event will feature a key opinion leader, Dr. Ann M. Gillenwater, Professor, Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, who will discuss the updated safety and efficacy findings from an interim evaluation of Rakuten Medical's open-label Phase 1b/2 study (ASP-1929-181/ClinicalTrials.gov Identifier: NCT04305795) of photoimmunotherapy using ASP-1929 in combination with anti-PD-1 therapy in first line recurrent and/or metastatic head and neck squamous cell carcinoma, which will be presented in a poster at ASCO 2024."

P1/2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Rakuten Medical Announces Recent Interim Data from Phase 1b/2 Clinical Trial of ASP-1929 Photoimmunotherapy in Combination with anti-PD-1 for First Line Recurrent and/or Metastatic Head and Neck Cancer to be Presented at ASCO 2024 (PRNewswire) - P1b/2 | N=74 | NCT04305795 | Sponsor: Rakuten Medical, Inc. | "Rakuten Medical...today announced the updated safety and efficacy findings from an interim evaluation of an open-label Phase 1b/2 study (ASP-1929-181/ClinicalTrials.gov Identifier: NCT04305795) of photoimmunotherapy using ASP-1929 in combination with anti-PD-1 for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). The data will be presented in a poster at the 2024 American Society of Clinical Oncology Annual Meeting (ASCO 2024) on June 2, 2024....Median overall survival (OS) was not reached at data cut-off, with an estimated survival rate of 52.4% at 24 months, and an objective response rate (ORR) of 35.3%. Adverse events were generally manageable, and the combination therapy was generally tolerated with an absence of synergistic serious adverse events."

P1/2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Rakuten Medical Announces Recent Interim Data from Phase 1b/2 Clinical Trial of ASP-1929 Photoimmunotherapy in Combination with anti-PD-1 for First Line Recurrent and/or Metastatic Head and Neck Cancer to be Presented at ASCO 2024 (PRNewswire) - "The encouraging early efficacy and safety outcomes warrant additional clinical studies to substantiate and reinforce these interim findings. Rakuten Medical recently completed a Type B End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA) for the combination of ASP-1929 photoimmunotherapy and anti-PD-1 in the first-line recurrent HNSCC setting and discussed the key details for a multi-regional registrational study. Based on these results, Rakuten Medical plans to initiate this global phase 3 clinical trial with a primary endpoint of OS in the second half of 2024."

FDA event • New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

ASP-1929 Photoimmunotherapy Combined With Pembrolizumab in Patients With Recurrent Head and Neck Cancer, With or Without Metastases (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: Rakuten Medical, Inc. | Active, not recruiting ➔ Terminated; Business decision

Trial termination • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Rakuten Medical Announces Poster Presentation and Booth Exhibition at ASCO 2024 Annual Meeting (PRNewswire) - "Rakuten Medical...announced that it will present a poster at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (ASCO 2024), which will be held in Chicago, Illinois from May 31 through June 4, 2024. The poster presentation will showcase the updated safety and efficacy findings from an interim evaluation of Rakuten Medical's open-label Phase 1b/2 study (ASP-1929-181/ClinicalTrials.gov Identifier: NCT04305795) of photoimmunotherapy using ASP-1929 in combination with anti-PD-1 therapy in recurrent or metastatic head and neck squamous cell carcinoma....In addition, a research team of Japanese physicians will present a poster on the latest findings from a multi-institutional observation study evaluating the efficacy and safety of photoimmunotherapy for recurrent nasopharyngeal cancer in clinical practice in Japan."

Observational data • P1/2 data • Nasopharyngeal Carcinoma • Squamous Cell Carcinoma of Head and Neck

ASP-1929 Photoimmunotherapy (PIT) Study in Patients With Recurrent Head/Neck Cancer (clinicaltrials.gov) - P2 | N=22 | Recruiting | Sponsor: Rakuten Medical, Inc. | Trial completion date: Sep 2025 ➔ Mar 2027

Trial completion date • Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

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

Rakuten Medical's Poster Presentation at AACR 2024 Demonstrates Reduction in Photoimmunotherapy-induced Edema in Mice with COX-2 Inhibition (PRNewswire) - "Rakuten Medical...announced a poster presentation of its study to manage edema following photoimmunotherapy at the 115th Annual Meeting of the American Association for Cancer Research....Prophylactic administration of a selective COX-2 inhibitor reduces the volume of edema associated with photoimmunotherapy by 30-50%. Reduced edema volume by 25%, even when administered post photoimmunotherapy. Suggested the COX-2 inhibitor may manage edema without compromising anti-tumor efficacy."

Preclinical • Oncology

Rakuten Medical Closes $119 Million Series E Financing to Further Develop its Alluminox Platform (PRNewswire) - "Rakuten Medical...announced the completion of a $119 million Series E preferred stock financing, including $45 million in new capital and the conversion of $74 million of convertible promissory notes with accrued interest. Rakuten Medical intends to further develop its proprietary Alluminox platform and contribute to the future of patients and healthcare around the world by allocating the funds raised for the following business priorities: Continuing efforts to accelerate its global Phase 3 clinical trial...; Supporting ongoing clinical trials and initiating new studies for Alluminox treatment using its three key assets (ASP-1929, RM-1995, and RM-0256), including combination therapy with anti-PD-1, which has shown promising early data that Rakuten Medical believes warrant additional clinical studies..."

Financing • Head and Neck Cancer