A Study of ASP-1929 Photoimmunotherapy in Combination With Pembrolizumab in First-line Treatment of Locoregional Recurrent Squamous Cell Carcinoma of the Head and Neck With No Distant Metastases

NCT06699212 | Recruiting Phase 3 DMC FDA Drug FDA Device

• 2 other identifiers: ASP-1929-381ECLIPSE
• Study Type: interventional
• Target: 412
• Locations: 3 countries
• Sites: 22

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

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

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  OS is defined as the time from randomization until death due to any cause.

  Up to approximately 48 months

Secondary Outcomes (15)

• Complete response rate (CRR) per modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) as assessed by central reviewer

  Up to approximately 48 months

• Overall response rate (ORR) per modified RECIST 1.1 as assessed by central reviewer

  Up to approximately 48 months

• Progression-free survival (PFS) per modified RECIST 1.1 as assessed by central reviewer

  Up to approximately 48 months

• OS rates at 12, 18, and 24 months

  12, 18, and 24 months

• Duration of Response (DOR) per modified RECIST 1.1 as assessed by central reviewer

  Up to approximately 48 months

Study Arms (3)

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

EXPERIMENTAL

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.

Combination Product: ASP-1929 Photoimmunotherapy; Biological: Pembrolizumab

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

EXPERIMENTAL

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.

Combination Product: ASP-1929 Photoimmunotherapy; Biological: Pembrolizumab

Pembrolizumab or pembrolizumab + chemotherapy (Control)

ACTIVE COMPARATOR

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

Biological: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: 5-fluorouracil; Drug: Paclitaxel; Drug: Docetaxel

Interventions

ASP-1929 Photoimmunotherapy COMBINATION_PRODUCT

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)

Also known as: cetuximab sarotalocan, PIT690 Laser System

320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab; 640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab

Pembrolizumab BIOLOGICAL

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

Also known as: Keytruda

320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab; 640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab; Pembrolizumab or pembrolizumab + chemotherapy (Control)

Carboplatin DRUG

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

Pembrolizumab or pembrolizumab + chemotherapy (Control)

Cisplatin DRUG

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

Pembrolizumab or pembrolizumab + chemotherapy (Control)

5-fluorouracil DRUG

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

Pembrolizumab or pembrolizumab + chemotherapy (Control)

Paclitaxel DRUG

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

Pembrolizumab or pembrolizumab + chemotherapy (Control)

Docetaxel DRUG

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

Pembrolizumab or pembrolizumab + chemotherapy (Control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Rakuten Medical, Inc.: lead

Study Sites (22)

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Tampa General Hospital

Tampa, Florida, 33606, United States

RECRUITING

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

WITHDRAWN

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

RECRUITING

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Aichi Cancer Center

Aichi, 464-8681, Japan

RECRUITING

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

RECRUITING

Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

RECRUITING

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

RECRUITING

Tottori University Hospital

Yonago, 683-8504, Japan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807377, Taiwan

RECRUITING

China Medical University

Taichung, 404327, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, 407219, Taiwan

RECRUITING

Chi Mei Hospital

Tainan, 736402, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

MacKay Memorial Hospital

Taipei, 104217, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

RECRUITING

Taipei Municipal Wanfang Hospital

Taipei, 116081, Taiwan

RECRUITING

Linkou Chang Gung Memorial Hospital

Taoyuan, 333423, Taiwan

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Carboplatin; Cisplatin; Fluorouracil; Paclitaxel; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Ethan Chen, MD

  Rakuten Medical, Inc.

  STUDY DIRECTOR

• Rebecca Cheng, MD

  Rakuten Medical, Inc.

  STUDY DIRECTOR

Central Study Contacts

ASP-1929-381 Study Team

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: November 21, 2024
• Study Start: December 24, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5); TW (9); US (8)