ASP-1929 + Pembrolizumab for Head and Neck Cancer

(ECLIPSE Trial)

Recruiting at 32 trial locations

Overseen By ASP-1929-381 Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Rakuten Medical, Inc.

Must be taking: Pembrolizumab

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, CNS metastases, 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

Compensation: Varies

Number of Visits: 3

Duration: Up to 24 months

412 Participants Needed

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 (PIT) combined with pembrolizumab to determine its effectiveness for people with recurrent squamous cell cancer in the head and neck. Researchers aim to assess whether this combination improves survival more effectively than standard treatments, such as pembrolizumab alone or with chemotherapy. Suitable participants have squamous cell cancer that has returned in the head or neck but has not spread elsewhere. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic chemotherapy, targeted therapy, or certain immunosuppressive treatments, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

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

A previous study found that the combination of ASP-1929 photoimmunotherapy and pembrolizumab was generally well-tolerated by patients. The research showed promising results, with patients responding well to the treatment. Another study confirmed that this combination was generally safe and effective for patients with head and neck cancer.

The FDA has already approved pembrolizumab alone for certain head and neck cancers, indicating a strong safety record. In a study involving 192 patients, pembrolizumab was found to be safe, with side effects like facial swelling occurring in 6% of patients.

Overall, these findings suggest that the combination of ASP-1929 with pembrolizumab is considered safe based on previous research, and pembrolizumab itself has a well-established safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ASP-1929 Photoimmunotherapy combined with pembrolizumab for head and neck cancer because it introduces a novel approach called photoimmunotherapy. Unlike standard treatments like chemotherapy or radiation, ASP-1929 uses a targeted antibody linked to a photosensitive dye that, when activated by a specific red light, directly attacks cancer cells while sparing healthy tissue. This targeted method could potentially lead to fewer side effects and improve precision in treatment. Additionally, combining this with pembrolizumab, an established immunotherapy, could enhance the immune system's ability to fight cancer more effectively. This combination could offer a more personalized and powerful treatment option for patients.

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

Research has shown that combining ASP-1929 photoimmunotherapy with pembrolizumab may effectively treat head and neck squamous cell carcinoma (HNSCC). In this trial, participants will receive either ASP-1929 photoimmunotherapy at varying dosages combined with pembrolizumab or a control treatment of pembrolizumab alone or with chemotherapy. A study found that the combination of ASP-1929 and pembrolizumab was generally well-tolerated and had positive effects in patients with recurring or spreading HNSCC. The KEYNOTE-048 study demonstrated that pembrolizumab alone improves survival rates in patients with this type of cancer. This suggests that adding ASP-1929 to pembrolizumab could enhance treatment effectiveness. ^{2 5 6 7 8}

Who Is on the Research Team?

Ethan Chen, MD

Principal Investigator

Rakuten Medical, Inc.

Rebecca Cheng, MD

Principal Investigator

Rakuten Medical, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with recurrent squamous cell carcinoma of the head and neck, which hasn't spread to distant parts of the body. Participants must not have had previous treatments that would interfere with this study.

Inclusion Criteria

Have results from testing of HPV status for oropharyngeal cancer

My cancer has not spread to distant parts of my body.

I am eligible for standard first-line treatment with pembrolizumab for my recurring head and neck cancer.

Exclusion Criteria

Life expectancy of less than 3 months

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

I have had a transplant of tissue or an organ from another person.

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 pembrolizumab or standard of care treatment

Up to 24 months

Every 3 to 6 weeks depending on treatment regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• ASP-1929 Photoimmunotherapy
• Pembrolizumab

Trial Overview The study tests ASP-1929 photoimmunotherapy combined with pembrolizumab against either pembrolizumab alone or along with chemotherapy (carboplatin or cisplatin and a choice of 5-fluorouracil, paclitaxel, or docetaxel). The goal is to see if combining therapies improves survival.

How Is the Trial Designed?

Group I: 640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab Experimental Treatment 2 Interventions

ASP-1929 640 mg/m\^2 IV infusion followed by illumination with 690 nm red light at accessible tumor sites using the investigational PIT690 Laser System (24 ± 4 hours after end of ASP-1929 infusion). Treatment with ASP-1929 PIT will be repeated every 4 to 6 weeks depending on clinical judgement of investigators. Pembrolizumab: 200 mg every 3 weeks (Q3W) IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab dosing regimen can be converted from 200 mg Q3W to 400 mg every 6 weeks (Q6W) at the investigator's discretion. Treatment in the experimental arm will start with the infusion of pembrolizumab on Cycle 1 Day 1 (C1D1) after which ASP-1929 Photoimmunotherapy will follow 7 days later, on Treatment 1 Day 1 (T1D1). Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 24 months.

Group II: 320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab Experimental Treatment 2 Interventions

ASP-1929 320 mg/m\^2 IV infusion followed by illumination with 690 nm red light at accessible tumor sites using the investigational PIT690 Laser System (24 ± 4 hours after end of ASP-1929 infusion). Treatment with ASP-1929 PIT will be repeated every 4 to 6 weeks depending on clinical judgement of investigators. Pembrolizumab: 200 mg every 3 weeks (Q3W) IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab dosing regimen can be converted from 200 mg Q3W to 400 mg every 6 weeks (Q6W) at the investigator's discretion. Treatment in the experimental arm will start with the infusion of pembrolizumab on Cycle 1 Day 1 (C1D1) after which ASP-1929 Photoimmunotherapy will follow 7 days later, on Treatment 1 Day 1 (T1D1). Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 24 months.

Group III: Pembrolizumab or pembrolizumab + chemotherapy (Control) Active Control 6 Interventions

Patients in the control arm will receive physician's choice SOC. Patients randomized to SOC may only be treated with one of the following SOC options: 1. Pembrolizumab alone 2. Pembrolizumab + platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) or taxane (paclitaxel or docetaxel) Pembrolizumab: 200 mg Q3W IV infusion over 30 minutes for the first 6 cycles. After the first 6 cycles, pembrolizumab administration can be switched from 200 mg Q3W to 400 mg Q6W at the investigator's discretion. Cisplatin or carboplatin: AUC 5 mg/mL/min or 100 mg/m\^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles 5-FU: 1000 mg/m\^2 IV infusion per day from Days 1-4 of each cycle, Q3W for up to 6 cycles Paclitaxel: At investigator's choice, 100 mg/m\^2 IV infusion on Day 1 and Day 8 of each 21-day cycle or paclitaxel 175 mg/m\^2 IV infusion on Day 1 of each 21-day cycle for up to 6 cycles Docetaxel: 75 mg/m\^2 IV infusion on Day 1 of each cycle, Q3W for up to 6 cycles

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

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 phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

The Keynote-048 study demonstrated that pembrolizumab significantly improves overall survival in patients with head and neck squamous cell carcinoma (HNSCC) who have measurable PD-L1 expression, leading to its approval as a first-line treatment in the USA.

In contrast, the EAGLE study found that durvalumab, with or without tremelimumab, did not improve response rates or overall survival compared to standard therapies, highlighting the need for more effective options for patients who do not respond to PD-1/PD-L1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for head and neck cancer : Highlights of the 2019 ASCO Annual Meeting]. Doescher, J., Busch, CJ., Wollenberg, B., et al.[2020]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

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 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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. 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.

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/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 ...

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. 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.

7. 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.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03769506

NCT03769506 | ASP-1929 Photoimmunotherapy (PIT) ... EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multiple-item scales that assess the ...