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

Phase 3

Not yet recruiting

• Conditions: Recurrent Head and Neck Squamous Cell Carcinoma
• Interventions: Combination Product: ASP-1929 Photoimmunotherapy; Biological: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: 5-fluorouracil; Drug: Paclitaxel; Drug: Docetaxel

• Registration Number: NCT06699212
• Lead Sponsor: Rakuten Medical, Inc.

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.
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Detailed Description

This is a phase 3 multicenter, randomized study designed to evaluate the efficacy and safety of ASP-1929 photoimmunotherapy (PIT) in combination with pembrolizumab versus pembrolizumab-based standard of care (SOC) as first-line treatment of locoregional recurrent HNSCC in patients with no distant metastases.
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-08-07
• Status Verified: 2024-11
• Study Start: 2024-11
• Study First Submitted QC: 2024-11-18
• Last Update Submitted: 2024-11-18
• Study First Posted: 2024-11-21
• Last Update Posted: 2024-11-21
• Primary Completion: 2028-09
• Study Completion: 2028-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 408

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.
• CPS ≥ 1 as determined locally by an FDA-approved test
• Have results from testing of HPV status for oropharyngeal cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab	ASP-1929 Photoimmunotherapy	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.
Pembrolizumab or pembrolizumab + chemotherapy (Control)	Paclitaxel	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
320 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab	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.
640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab	ASP-1929 Photoimmunotherapy	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.
640 mg/m^2 ASP-1929 Photoimmunotherapy + pembrolizumab	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.
Pembrolizumab or pembrolizumab + chemotherapy (Control)	Pembrolizumab	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
Pembrolizumab or pembrolizumab + chemotherapy (Control)	Carboplatin	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
Pembrolizumab or pembrolizumab + chemotherapy (Control)	Cisplatin	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
Pembrolizumab or pembrolizumab + chemotherapy (Control)	5-fluorouracil	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
Pembrolizumab or pembrolizumab + chemotherapy (Control)	Docetaxel	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

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to approximately 48 months	OS is defined as the time from randomization until death due to any cause.

Secondary Outcome Measures

Name	Time	Method
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	CRR is defined as the proportion of patients with best overall response of CR
Overall response rate (ORR) per modified RECIST 1.1 as assessed by central reviewer	Up to approximately 48 months	ORR is defined as the proportion of patients with best overall response of CR or partial response (PR)
Progression-free survival (PFS) per modified RECIST 1.1 as assessed by central reviewer	Up to approximately 48 months	PFS is defined as the time from randomization to the first documented tumor progression or death due to any cause, whichever occurs first.
OS rates at 12, 18, and 24 months	12, 18, and 24 month	OS rates at 12, 18, and 24 months are defined as the proportions of patients who are alive at these time points
Duration of Response (DOR) per modified RECIST 1.1 as assessed by central reviewer	Up to approximately 48 months	DOR is defined as the time from first response (CR or PR) that is subsequently confirmed to the time of disease progression or death due to any cause, whichever occurs first
Duration of CR per modified RECIST 1.1 as assessed by central reviewer	Up to approximately 48 months	Duration of CR is defined as the time from first response (CR) that is subsequently confirmed to the time of disease progression or death due to any cause, whichever occurs first
Time to response (TTR)	Up to approximately 25 months	TTR is defined as the time from randomization to the first response (CR or PR)
CRR from randomization to End of Treatment per modified RECIST 1.1 as assessed by the central reviewer	Up to approximately 25 months	CRR from randomization to end of treatment is defined as the proportion of patients with the best overall response of CR, where the CR occurs anytime during the study treatment period (e.g., CR after PD will be counted).
Proportion of treatment-emergent adverse events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Up to approximately 48 months	TEAEs refer to any AEs that begin or worsen on or after the start of any study treatment through 30 days after the last dose of any study treatment and any additional irAEs that begin between 30 days and 90 days after the last dose of anti-PD1 treatment. In addition, any serious AE with an onset date more than 30 days after the last dose of study treatment a...
Proportion of treatment-related adverse events (TRAEs) by CTCAE v5.0	Up to approximately 48 months	Any TEAE (defined in Outcome 10) for which there is a reasonable possibility that the investigational treatment caused the adverse event.
Proportion of serious adverse events (SAEs) by CTCAE v5.0	Up to approximately 48 months	An AE or suspected adverse reaction is considered 'serious' if, in the view of either the Investigator or Sponsor, it meets one or more of the following criteria (21 CFR 312.32 (a)): Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity...
Quality of Life assessment: EORTC Core Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30)	Up to approximately 28 months	EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The summed scores of Functional scales, Symptom scales, and Global health status domains of EORTC-QLQ-C30 are compared between treatment arms.
Quality of Life assessment: EORTC Quality of Life Questionnaire Head and Neck Module (QLQ-H&N35)	Up to approximately 28 months	EORTC QLQ-H\&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. The summed scores of the scales of EORTC-QLQ-H\&N35 are compared between treatment arms.
Population PK - Clearance (Experimental Arm Only)	Before the start of 1st ASP-1929 infusion, 0.25 hours, 4 hours, 24 hours, 192 hours, 360 hours after end of 1st infusion; same timepoints for 2nd ASP-1929 infusion	A structural compartment model with population factors such as age, race, ECOG, and sex will be utilized to analyze concentration levels. The clearance estimates associated with different factors will be reported.
Presence of anti-drug antibodies (ADAs) (Experimental Arm Only)	Before the start of 1st ASP-1929 infusion, 15 days after end of 1st infusion; same timepoints for 2nd ASP-1929 infusion	Average concentration level of ADAs at baseline and 15 days after ASP-1929 infusion for the first 2 treatments.

Trial Locations

Locations (1)

Cancer Clinic; 🇺🇸 Lexington, Kentucky, United States