Photoimmunotherapy for Head and Neck Cancer

Not currently recruiting at 65 trial locations

Overseen By Ethan Chen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Rakuten Medical, Inc.

Must not be taking: Anticancer monoclonal antibodies

Disqualifiers: Metastatic disease, Active cancer, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ASP-1929 Photoimmunotherapy, which combines a drug with light to target cancer cells, for head and neck cancer that has returned or persisted after treatment. Researchers aim to determine if this therapy is more effective than standard treatments, such as certain chemotherapy drugs. Individuals with squamous cell carcinoma in the head and neck area, who have tried at least two other treatments without success, and have tumors accessible to light, may be suitable for this trial. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had chemotherapy, targeted therapy, or radiation within 2 weeks before the trial starts, and you must have recovered from any side effects of previous treatments. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have had chemotherapy, targeted therapy, or radiation within 2 weeks before starting the trial. You also cannot have had monoclonal antibody therapy or investigational treatments within 4 weeks before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ASP-1929 photoimmunotherapy was generally well tolerated in earlier studies. Patients with head and neck cancer who received ASP-1929 alongside other treatments achieved promising results. Early data from these studies suggested the treatment was safe for humans, with most patients experiencing manageable side effects. Serious side effects were rare, making the treatment a potential option for those seeking new therapies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for head and neck cancer, such as docetaxel, cetuximab, methotrexate, and paclitaxel, ASP-1929 Photoimmunotherapy offers a novel approach by combining a drug with a special light-activated therapy. This treatment uses a targeted antibody that binds specifically to cancer cells and, when activated by near-infrared light, it can destroy those cells while sparing the surrounding healthy tissue. Researchers are excited about this because it potentially offers a more precise and less toxic treatment option, which could lead to fewer side effects and improved outcomes for patients.

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

Studies have shown that ASP-1929 photoimmunotherapy can effectively treat recurring head and neck cancer. In this trial, some participants will receive ASP-1929 photoimmunotherapy. Research indicates that patients receiving ASP-1929, especially when combined with pembrolizumab (a treatment that helps the immune system fight cancer), showed promising survival and response rates. Initial findings suggest patients generally tolerate it well. These results are particularly encouraging for those who have not succeeded with at least two other treatments. ^{1 2 3 5 6}

Who Is on the Research Team?

Ethan Chen, MD

Principal Investigator

Rakuten Medical

Are You a Good Fit for This Trial?

This trial is for adults with recurrent head and neck cancer who have tried at least two other treatments without success. They must be in relatively good health (ECOG score of 0 or 1), not pregnant, agree to use contraception, and have a life expectancy over six months. The cancer should be measurable by CT scan and accessible for treatment but not spread to distant areas or invading major blood vessels.

Inclusion Criteria

I have finished radiation therapy aimed at curing cancer in my head or neck.

Have a life expectancy of > 6 months, based on Investigator judgment

I agree to use contraception for 6 months after my last treatment.

Exclusion Criteria

You have experienced severe allergic reactions to cetuximab infusions in the past.

I haven't had chemotherapy, targeted therapy, or radiation in the last 2 weeks and have recovered from any side effects.

My tumor is affecting a major blood vessel but has been treated to prevent bleeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ASP-1929 Photoimmunotherapy or physician's choice standard of care. ASP-1929 treatment cycles are repeated up to 8 times within 12 months.

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of progression-free survival and overall survival.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• ASP-1929 Photoimmunotherapy

Trial Overview The study compares ASP-1929 Photoimmunotherapy (PIT) with the physician's choice of standard care. Participants will either receive this new therapy that combines a drug with light exposure on the tumor area or get the usual treatment options available for their condition.

How Is the Trial Designed?

Group I: ASP-1929 Photoimmunotherapy Experimental Treatment 1 Intervention

Use of ASP-1929 Photoimmunotherapy

Group II: Physician's Choice SOC Active Control 1 Intervention

docetaxel, cetuximab, methotrexate, paclitaxel

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS6122

A phase 3 randomized study of ASP-1929 ... The objective of this pivotal phase 3 study is to further evaluate the efficacy and safety of ASP-1929 PIT in combination with pembrolizumab in rHNSCC.

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.