Photoimmunotherapy + Anti-PD1 for Head and Neck Cancer

Not currently recruiting at 6 trial locations

Overseen By Ashok Srivatasava

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Rakuten Medical, Inc.

Must be taking: Anti-PD1 therapy

Must not be taking: Chronic steroids, Immunosuppressives

Disqualifiers: Autoimmune disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for certain types of head and neck cancer and skin cancer. It uses photoimmunotherapy (a light-based cancer treatment) alongside anti-PD1 therapy, which helps the immune system combat cancer cells. The trial divides participants into three groups, each focusing on different stages of head and neck squamous cell carcinoma or cutaneous squamous cell carcinoma. It suits those with advanced or recurring cancer that cannot be treated with surgery or radiation and who have a disease site that can be exposed to light. Participants should have previously received anti-PD1 therapy without success. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any other form of immunosuppressive therapy, you may need to stop these at least 14 days before starting the trial. Also, if you are receiving anti-PD1 therapy, you must continue it if you are in Sub-study 3.

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

A previous study found that ASP-1929 photoimmunotherapy combined with pembrolizumab was generally well tolerated. Patients demonstrated promising survival and response rates. Similarly, cemiplimab has maintained a good safety record in treating advanced skin cell cancers. It was tested in many patients, with some experiencing common side effects, which were usually manageable. Pembrolizumab, already approved for certain head and neck cancers, also has a well-established safety record. Many patients tolerated it well, with side effects similar to those of other cancer treatments. Overall, past research has shown these treatments to be generally safe, but discussing any concerns with a healthcare provider is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine photoimmunotherapy with anti-PD1 therapies, offering a fresh approach to tackling head and neck cancer and cutaneous squamous cell carcinoma (cuSCC). Unlike traditional treatments like surgery, radiation, or chemotherapy, which can have significant side effects, ASP-1929 uses a unique mechanism where light activates a drug bound to cancer cells, sparing healthy tissue. By adding Cemiplimab and Pembrolizumab, which are immune checkpoint inhibitors, this combination aims to supercharge the body's immune response against cancer, possibly improving the effectiveness and speed of treatment. This innovative approach could lead to better outcomes and fewer side effects for patients.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that ASP-1929, one of the treatments in this trial, yields promising results for head and neck cancer when combined with anti-PD1 therapy. In this trial, some participants will receive ASP-1929 with pembrolizumab. Studies have found this combination leads to good survival rates and positive patient responses, with patients living a median of 25.6 months. Other participants will receive cemiplimab, which has effectively treated advanced cutaneous squamous cell carcinoma by significantly reducing the risk of recurrence. Pembrolizumab, another treatment option in this trial, has also improved survival rates in head and neck cancer patients, particularly when combined with chemotherapy. Overall, these treatments show promising potential in managing these cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Toshiaki Suzuki, MD

Principal Investigator

Rakuten Medical, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced squamous cell cancers in the head, neck, or skin. Participants must have at least one tumor accessible to light treatment and measurable disease. They should be relatively healthy (ECOG 0-1), not have had recent systemic cancer therapy (except if over 6 months ago as part of multimodal treatment), and agree to use effective contraception methods.

Inclusion Criteria

My skin cancer is advanced, cannot be removed by surgery or treated with radiation.

At least one site of disease accessible to light illumination

Measurable disease by modified RECIST 1.1

Exclusion Criteria

I haven't had radiation or similar treatments in the last 4 weeks, or I've recovered from their side effects.

I am currently on medication for an infection.

I have upcoming procedures that involve significant light exposure within 4 weeks after my ASP-1929 PIT treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ASP-1929 photoimmunotherapy in combination with anti-PD1 therapy for up to 24 months

24 months

Regular clinical assessments for safety, tolerability, and disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ASP-1929
• Cemiplimab
• Pembrolizumab

Trial Overview The study tests ASP-1929 photoimmunotherapy combined with anti-PD1 drugs Pembrolizumab or Cemiplimab in patients with recurrent/metastatic head & neck squamous cell carcinoma or cutaneous squamous cell carcinoma that can't be treated by surgery/radiation.

How Is the Trial Designed?

Group I: Sub-study 3- 2L cuSCC Experimental Treatment 2 Interventions

Locally advanced or metastatic cutaneous squamous cell carcinoma

Group II: Sub-study 2- 1L cuSCC Experimental Treatment 2 Interventions

Locally advanced or metastatic cutaneous squamous cell carcinoma

Group III: Sub-study 1- 1L HNSCC Experimental Treatment 2 Interventions

Recurrent locally advanced and/or metastatic head and neck squamous cell carcinoma

Who Is Running the Clinical Trial?

Rakuten Medical, Inc.

Lead Sponsor

Trials

7

Recruited

630+

Published Research Related to This Trial

In a phase Ia clinical trial involving 32 patients with advanced head and neck cancer, atezolizumab demonstrated a tolerable safety profile, with 66% of patients experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment showed promising efficacy, with 22% of patients achieving objective responses and a median overall survival of 6.0 months, indicating potential benefits regardless of HPV status or PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. Colevas, AD., Bahleda, R., Braiteh, F., et al.[2022]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

In a phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a phase III trial, pembrolizumab, a single-agent treatment, showed significant effectiveness in patients with head and neck tumors that had high PD-L1 expression, leading to deep and lasting responses.

This study highlights the potential of pembrolizumab as a first-line therapy for this specific group of cancer patients, suggesting a targeted approach based on PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

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. 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 ...

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

Press Releases Combination therapy showed promising initial efficacy with a median OS of 25.6 months and a preliminary manageable safety profile in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06699212

NCT06699212 | A Study of ASP-1929 ... The goal of this clinical trial is to learn if ASP-1929 photoimmunotherapy (PIT) in combination with pembrolizumab works to treat recurrent squamous cell ...

6. 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.