Recruiting
Phase 3

ASP-1929 & Pembrolizumab

Sponsor:

Rakuten Medical, Inc.

Code:

NCT06699212

Conditions

Recurrent Head and Neck Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ASP-1929 Photoimmunotherapy

Pembrolizumab

Carboplatin

Cisplatin

5-fluorouracil

Study Details

Brief summary:

The goal of this clinical trial is to learn if ASP-1929 photoimmunotherapy (PIT) in combination with pembrolizumab works to treat recurrent squamous cell cancer of the head and neck (HNSCC) with no distant metastases. It will also learn about the safety of ASP-1929 PIT in combination with pembrolizumab.

Researchers will compare ASP-1929 PIT in combination with pembrolizumab to pembrolizumab alone or pembrolizumab plus chemotherapy (carboplatin or cisplatin, plus 5-fluorouracil or paclitaxel or docetaxel) according to physician's choice (control arm).

The overall primary study hypothesis being tested is whether ASP-1929 PIT plus pembrolizumab combination treatment improves the overall survival (OS) of the population defined by the inclusion/exclusion criteria over the control arm.

Conditions

Recurrent Head and Neck Squamous Cell Carcinoma

Study ID

NCT06699212

Start date

Dec 24, 2024

Status verified date

Oct, 2025

Completion date

Sep, 2028

Anticipated

Primary completion date

Sep, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Histological or cytological evidence of squamous cell carcinoma of a head and neck primary site (per American Joint Committee on Cancer \[AJCC\], other than nasopharynx or cuSCC).
  • Appropriate for SOC first-line treatment of their recurrent head and neck cancer with pembrolizumab ± chemotherapy.
  • No known history of any distant metastatic disease (M1 by AJCC eighth edition).
  • Tumors with at least one PIT-accessible and RECIST 1.1 measurable lesion as assessed by investigator.
  • Anti-PD-1 and anti-PD-L1-treatment naïve.
  • Combined positive score (CPS) ≥ 1 as determined locally by an FDA-approved test
  • Have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of screening
  • Adequate hematologic, renal, and hepatic organ function
  • Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and must be willing to use a highly effective birth control while on study or be surgically sterile or abstain from heterosexual sexual activity for the course of the study through 180 days after the last dose of study treatment. Male patients must agree to use a highly effective method of contraception starting with the first dose of study medication through 120 days after the last dose of study treatment.

Exclusion Criteria:

  • Diagnosed and/or treated for additional malignancy within 2 years before randomization except for those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal cell skin cancer, localized prostate cancer, or ductal carcinoma in situ). Patients with a history of other prior cancer treated with complete surgical resection and with no evidence of disease may be eligible based on discussion with the Medical Monitor.
  • History of significant (Grade ≥ 3) cetuximab infusion reactions
  • Prior allogeneic tissue/solid organ transplant
  • Known or active central nervous system metastases and/or carcinomatous meningitis
  • Life expectancy of less than 3 months
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Evidence of interstitial lung disease or current active, noninfectious pneumonitis
  • Active infection requiring systemic therapies such as antibiotic, antifungal, or antiviral intervention
  • Known or active bacterial, viral, or fungal infection including tuberculosis, Hepatitis B (e.g., HBV DNA is detected), or Hepatitis C (e.g., RNA \[qualitative\] is detected)
  • Known history of testing positive for human immunodeficiency virus or acquired immunodeficiency syndrome (AIDS)-related illness
  • Prior or ongoing Grade ≥ 3 tumor hemorrhage within 12 weeks of randomization
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Prior systemic chemotherapy or targeted small molecule therapy or radiation therapy within 2 weeks of C1D1 or has not recovered (i.e., Grade ≤ 1 or at baseline) from adverse events (AEs) due to previously administered agent
  • Prior anticancer monoclonal antibody therapy or investigational agent or intervention within 4 weeks of C1D1 or has not recovered (i.e., Grade ≤ 1 or at baseline) from AEs due to previously administered agent
  • Prior receipt of ASP-1929 at any time
  • Receiving chronic systemic steroid therapy (in doses exceeding 10 mg per day of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to randomization
  • Received a live vaccine within 4 weeks of randomization; seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
  • Requiring future examinations or treatments within 4 weeks after an ASP-1929 PIT treatment exposing the patient to significant light (e.g., eye examinations, surgical procedures, endoscopy) that is unrelated to the ASP-1929 PIT treatment
  • Major surgery or significant traumatic injury within 4 weeks before randomization, or anticipation of the need for major surgery during the course of study treatment

Study Design

Enrollment

412 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab

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.

experimental: 640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab

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.

active comparator: Pembrolizumab or pembrolizumab + chemotherapy (Control)

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

Interventions

ASP-1929 Photoimmunotherapy

ASP-1929 IV infusion followed by illumination with light dose of 50 J/cm\^2 for superficial lesions and 100 J/cm for interstitial lesions within 24 +/- 4 hours after the end of ASP-1929 infusion (up to 24 months)

Pembrolizumab

200 mg Q3W or 400 mg Q6W, IV infusion over 30 minutes (up to 24 months)

Carboplatin

Area under the curve (AUC) 5 mg/mL/min IV infusion, Q3W up to 6 cycles

Cisplatin

100 mg/m\^2 IV infusion, Q3W up to 6 cycles

5-fluorouracil

1000 mg/m\^2 per day from Days 1-4 of each cycle, IV infusion, Q3W up to 6 cycles

Paclitaxel

100 mg/m\^2 IV infusion given on Days 1 and 8, Q3W up to 6 cycles or 175 mg/m\^2 IV infusion given on Day 1, Q3W up to 6 cycles

Docetaxel

75 mg/m\^2 IV Infusion, Q3W up to 6 cycles

Primary outcome measure

  • Overall survival (OS) [ Time Frame: Up to approximately 48 months ]

Central Contacts and Locations

Central contacts

ASP-1929-381 Study Team

858-207-3113clinicaltrialinfo@rakuten-med.com

Locations

City of Hope

Recruiting

Duarte, California, United States, 91010

Contacts

Elizabeth Kim

elikim@coh.org

Principal Investigator:

Krupal Patel, MD

University of Miami

Recruiting

Miami, Florida, United States, 33136

Contacts

Dhamini Gajjala

dxg2825@med.miami.edu

Principal Investigator:

Francisco Jose Civantos, MD

Tampa General Hospital

Recruiting

Tampa, Florida, United States, 33606

Contacts

Monica Rengifo Pardo

mrengifopardo@TGH.org

Principal Investigator:

Matthew Mifsud, MD

Thomas Jefferson University, Sidney Kimmel Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contacts

Jack Peters

john.peters2@jefferson.edu

Principal Investigator:

David Cognetti, MD

Rhode Island Hospital

Recruiting

Providence, Rhode Island, United States, 02903

Contacts

Sopha Dionson

sdionson@brownhealth.org

Principal Investigator:

Ariel Birnbaum, MD

Avera Cancer Institute

Recruiting

Sioux Falls, South Dakota, United States, 57105

Contacts

Brenna O'Bryan

medoncresearch@avera.org

Principal Investigator:

William Spanos, MD

University of Texas, MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Wendy Leak

wjleak@mdanderson.org

Principal Investigator:

Ann Gillenwater, MD

More Information

Sponsor

Rakuten Medical, Inc.

Last update posted

Oct 15, 2025

Last verified

Oct, 2025

Keywords

  • HNSCC
  • Squamous Cell Carcinoma of Head and Neck
  • Head and Neck Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of the Head and Neck
  • immunotherapy
  • medical device
  • laser phototherapy
  • Epidermal Growth Factor Receptor
  • PD-1 Inhibitor
  • Immune Checkpoint Inhibitor
  • Alluminox
  • Rakuten Medical
  • ASP-1929
  • photoimmunotherapy
  • head and neck

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Rakuten Medical, Inc. on 2025-10-15.