Photoimmunotherapy for Head and Neck Cancer

Overseen By Rakuten Medical Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rakuten Medical, Inc.

Must not be taking: Photosensitizing medications

Disqualifiers: Metastatic disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called photoimmunotherapy for individuals with operable head, neck, or skin cancer. The treatment uses a special drug, ASP-1929 (also known as RM-1929), and a light system to target and destroy cancer cells. The goal is to determine the safety and effectiveness of this method before surgery. Candidates should have a tumor in the head, neck, or on the skin's surface that can be treated with this method. Participants must have a tumor that is accessible and measurable and should not have received certain recent cancer treatments. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications to join the trial?

The trial requires that you stop taking any photosensitizing medications 30 days before starting the treatment. Other than that, the protocol does not specify if you need to stop taking other medications, so it's best to discuss your current medications with the trial team.

What prior data suggests that ASP-1929 Photoimmunotherapy is safe for head and neck cancer patients?

Previous studies have shown that ASP-1929 photoimmunotherapy is generally well-tolerated. Researchers tested this treatment alongside pembrolizumab, and most patients with head and neck cancer handled it well. The trials demonstrated promising results for patient survival and response rates. Although specific side effects were not detailed, overall feedback suggests the treatment is manageable for most patients. This background may provide some confidence in its safety for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Researchers are excited about ASP-1929 Photoimmunotherapy because it offers a novel approach to treating head and neck cancer. Unlike standard treatments such as surgery, chemotherapy, and radiation, ASP-1929 combines a drug with a special type of light therapy, known as photoimmunotherapy, to specifically target cancer cells. This treatment uses an antibody linked to a dye that, once activated by near-infrared light, helps destroy cancer cells while sparing healthy tissue. This targeted method could potentially reduce side effects and improve precision, making treatment more effective and tolerable for patients.

What evidence suggests that ASP-1929 Photoimmunotherapy might be an effective treatment for head and neck cancer?

Research has shown that ASP-1929 photoimmunotherapy holds promise for treating head and neck cancer. Studies have found that patients generally tolerate it well, and it can improve survival rates and treatment responses. In this trial, participants will receive ASP-1929 photoimmunotherapy, which uses light to activate a drug that targets and destroys cancer cells. Current findings suggest it could be a strong option for those with recurring or hard-to-treat cancers. ^{2 3 4 5 6}

Who Is on the Research Team?

Vassiliki Saloura, MD

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults with resectable head and neck or cutaneous squamous cell carcinoma. Candidates must have a tumor that can be illuminated and imaged, no distant metastasis, not use photosensitizing drugs, and have good organ function. Women of childbearing age must test negative for pregnancy and agree to birth control; men must also agree to contraception.

Inclusion Criteria

I can provide a recent tumor sample for the study.

I am fully active or restricted in physically strenuous activity but can do light work.

I am not pregnant or breastfeeding and agree to use birth control or abstain from sex during the study and for 60 days after.

Exclusion Criteria

Unwilling or unable to follow protocol requirements

I haven't had treatment for another cancer with high risk of spreading in the last 3 years.

Known infection or detection of active Hepatitis B (eg, HBsAg positive), Hepatitis C (eg, RNA [qualitative]), or SARS-CoV-2 (qualitative)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ASP-1929 640 mg/m^2 treatment by IV infusion followed by photoimmunotherapy (PIT) using the PIT690 Laser System

3 weeks

1 visit (in-person) for treatment, 1 visit (in-person) for surgery

Follow-up

Participants are monitored for recurrence-free survival and other outcomes after surgery

12 months

Long-term Follow-up

Participants are monitored for overall survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• ASP-1929 Photoimmunotherapy

Trial Overview The study tests ASP-1929 Photoimmunotherapy (PIT) in patients with operable primary or recurrent head/neck or skin cancer. It's an open-label, single-arm Phase 2 trial focusing on the effects of PIT when used before standard surgery.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

ASP-1929 640 mg/m\^2 treatment by intravenous (IV) infusion followed approximately 24 hours later by illumination (also termed as photoimmunotherapy \[PIT\]) of tumor(s) using the PIT690 Laser System with a 690 nm light dose of 50 J/cm\^2 for superficial illumination and 100 J/cm of diffuser length for interstitial illumination. During the illumination procedure, fluorescence of the IR700 component of ASP-1929 will be imaged with a Shimadzu Fluorescence Imaging System camera. Patients will undergo standard of care surgery with or without chemotherapy or radiation approximately 21 days after ASP-1929 PIT treatment.

ASP-1929 Photoimmunotherapy is already approved in Japan for the following indications:

Approved in Japan as ASP-1929 for:

• Unresectable locally advanced or recurrent head and neck cancer

Who Is Running the Clinical Trial?

Rakuten Medical, Inc.

Lead Sponsor

Trials

7

Recruited

630+

Shimadzu Corporation

Collaborator

Trials

1

Recruited

9+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Acute dermatitis is a common side effect of radiation therapy in head and neck cancer, and a review of 17 studies involving 950 patients found no strong evidence favoring any specific treatment for skin toxicity.

The review highlights the need for well-designed randomized controlled trials that include quality of life assessments to better evaluate the effectiveness of interventions for managing radiation-induced dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and treatment of radiation-induced acute dermatitis in head and neck cancer patients: a systematic review. Iacovelli, NA., Galaverni, M., Cavallo, A., et al.[2019]

This study aims to determine if a reminder app can reduce the rates of severe radiation dermatitis and oral mucositis in patients undergoing radiotherapy for head-and-neck cancer, with 168 patients expected to be randomized into two groups: one receiving standard care and the other receiving standard care plus the app.

The primary goal is to achieve a clinically relevant reduction of at least 20% in grade ≥2 radiation dermatitis, which could significantly improve patient outcomes and quality of life during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy-related skin toxicity (RAREST-02): A randomized trial testing the effect of a mobile application reminding head-and-neck cancer patients to perform skin care (reminder app) on radiation dermatitis. Rades, D., Narvaez, CA., Doemer, C., et al.[2021]

Photodynamic therapy (PDT) is an effective treatment for superficial head and neck tumors, utilizing a phototoxic drug activated by laser light to destroy cancer cells.

While there is substantial case series data supporting the use of PDT, particularly for dysplastic changes and superficial carcinomatosis, there is a lack of randomized clinical trials to fully validate its efficacy across different tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Photodynamic Therapy for Neoplasms of the Head and Neck. Civantos, FJ., Karakullukcu, B., Biel, M., et al.[2019]

RM-1929 near-infrared photoimmunotherapy (NIR-PIT) shows promising efficacy in treating unresectable and/or recurrent head and neck squamous cell carcinoma (HNSCC), with disease control rates between 66.7% and 100% and overall response rates from 43.3% to 100% based on case reports and clinical trial data.

The treatment is well-tolerated, with low-grade side effects such as localized pain and edema, and it does not significantly impact patients' quality of life, making it a viable option for managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of RM-1929 Near-Infrared Photoimmunotherapy Clinical Efficacy for Unresectable and/or Recurrent Head and Neck Squamous Cell Carcinoma. Miyazaki, NL., Furusawa, A., Choyke, PL., et al.[2023]

Novel immune checkpoint inhibitors, particularly PD-1 antibodies like nivolumab, have shown significant efficacy in improving survival for patients with head and neck squamous cell carcinoma (HNSCC) after platinum-based therapy, leading to a breakthrough therapy designation by the FDA.

Ongoing clinical trials are exploring the use of these immunotherapies in first-line palliative treatment and neoadjuvant settings, but there is a need for reliable testing systems and predictive markers to ensure patient safety and cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapeutic studies of head and neck tumors : Highlights of the 2016 ASCO Annual Meeting]. Busch, CJ., Laban, S., Knecht, R., et al.[2019]

In a study involving 39 patients with recurrent head and neck squamous cell carcinoma (rHNSCC), RM-1929 photoimmunotherapy demonstrated a confirmed objective response rate of 26.7% and a median overall survival of 9.30 months, indicating meaningful efficacy in a heavily pretreated population.

The treatment was generally well tolerated, with no dose-limiting toxicities observed in the initial dose-finding phase, although 63.3% of patients experienced adverse events of Grade 3 or higher, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2a, open-label, multicenter study of RM-1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma. Cognetti, DM., Johnson, JM., Curry, JM., et al.[2022]

Recent advancements in cancer immunotherapy, particularly targeted immune checkpoint therapies, have significantly improved survival rates for patients with advanced tumors, including head and neck cancers.

Combining immune checkpoint inhibitors with standard treatments like surgery, radiation, and chemotherapy offers expanded therapeutic options, addressing the unique challenges posed by head and neck tumors that evade immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibitors in Cancer Therapy: Clinical Benefits for Head and Neck Cancers. Ettl, T., Grube, M., Schulz, D., et al.[2022]

Red light phototherapy (RLPT) significantly reduced the severity of radioactive dermatitis (RD) in patients with head and neck cancer, with most patients in the experimental group experiencing milder grades of dermatitis (0-2) compared to the control group (2-3).

Patients receiving RLPT reported lower levels of skin pain during treatment, indicating that RLPT not only helps in healing but also improves the overall quality of life for patients undergoing radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of red light phototherapy in the treatment of radioactive dermatitis in patients with head and neck cancer. Zhang, X., Li, H., Li, Q., et al.[2023]

Photodynamic therapy (PDT) and photodiagnosis (PD) present promising alternatives for treating head and neck cancer, potentially improving outcomes for patients with various stages of the disease, from in situ to recurrent cases.

Current standard treatments like surgery and radiation are highly morbid, and PDT/PD could offer less invasive options, yet these therapies are still underutilized despite the availability of effective photosensitizers like Photofrin®, Photosan, and Foscan®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical photodynamic therapy of head and neck cancers-A review of applications and outcomes. Allison, RR., Cuenca, RE., Downie, GH., et al.[2014]

The combination of immunotherapy with radiotherapy and chemotherapy shows promising synergistic effects in treating recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC), enhancing the body's antitumor immune response.

There is a growing recognition of phenomena like pseudoprogression, where treatment may initially appear ineffective on scans, highlighting the need for reliable biomarkers to better understand and predict these effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy in head and neck squamous cell carcinoma : Abscopal effects in combination with radiotherapy, extraordinary responses in combination with chemotherapy, and pseudoprogression]. Brix, N., Dunn, L., Seiwert, T., et al.[2020]

In patients with high-risk locally advanced head and neck cancers, the addition of cisplatin to postoperative radiotherapy significantly improves locoregional control and disease-free survival, particularly for those with microscopically involved surgical margins or extracapsular extension of the tumor.

Patients with two or more involved lymph nodes without extracapsular extension did not benefit from the addition of chemotherapy, indicating that specific risk factors should guide treatment decisions for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Bernier, J., Cooper, JS., Pajak, TF., et al.[2022]

Recent trials presented at the ASCO 2015 focused on optimizing concomitant chemoradiotherapy (CRT) for locally advanced head and neck cancer, particularly examining dosage and sequencing of cisplatin, especially in HPV-positive patients.

Alternative treatments to cisplatin, such as carboplatin and targeted therapies, are being explored, along with comparisons between concomitant and sequential CRT approaches, indicating a shift towards personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The most important study results concerning nonsurgical primary treatment of locally advanced head and neck cancer: Highlights of the ASCO Meeting 2015]. Gliese, A., Busch, CJ., Knecht, R.[2018]

Significant progress has been made in identifying clinical and pathologic features that help stratify head and neck cancer patients by their risk of relapse and second cancers, allowing for more targeted adjuvant treatments.

Adjuvant therapy is now recognized as a crucial component of a comprehensive treatment strategy for head and neck cancer, aimed at maximizing tumor control while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy in head and neck cancer. Vikram, B.[2019]

Immunotherapy, particularly checkpoint inhibitors, has emerged as a promising treatment for various cancers, including those in the head and neck region, primarily used in palliative care.

Current clinical trials are exploring the use of checkpoint inhibitors both as standalone treatments and in combination with other therapies, indicating ongoing advancements in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immuno-, radio-, and chemotherapeutic studies in head and neck cancer : Highlights of the ASCO Annual Meeting 2017]. Schuler, PJ., von Witzleben, A., Doescher, J., et al.[2019]

Combined modality treatment using cisplatin and radiotherapy for head and neck cancer shows promising results in local control and survival rates, leading to the initiation of three Phase III trials for advanced stages of various cancers in this region.

While the combination treatment can increase mucosal toxicity and myelosuppression, it does not hinder the delivery of standard radiotherapy, suggesting that patient compliance can be managed effectively during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin and radiotherapy in the management of locally advanced head and neck cancer. Forastiere, AA.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6083

Recent safety and efficacy findings from a phase 1b/2 open ... ASP-1929 PIT in combination with anti-PD-1 therapy was generally well tolerated. Initial data demonstrate promising overall survival and response rates.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40852760/

Safety and Efficacy Findings From a Phase Ib/II Study of ... ASP-1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC.

3. rakuten-med.com rakuten-med.com/us/news/press-releases/2025/09/18/7922/

Press Releases ASP-1929 photoimmunotherapy in combination with pembrolizumab is currently under investigation in a global Phase 3 clinical trial as a first- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03769506

NCT03769506 | ASP-1929 Photoimmunotherapy (PIT) ... ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/​Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy. ClinicalTrials.gov ID ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hed.70014

Safety and Efficacy Findings From a Phase Ib/II Study of ... ASP-1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC. 1 ...

6. rakuten-med.com rakuten-med.com/us/news/press-releases/2025/01/23/7878/

Press Releases This trial will evaluate whether the combination of ASP-1929 photoimmunotherapy with pembrolizumab can harness synergistic antitumor effects.