Clinical trial NCT06699212: 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
Official title: A Phase 3 Multicenter, Randomized, Open-label Study of ASP-1929 Photoimmunotherapy in Combination With Pembrolizumab Versus Standard of Care in the First-line Treatment of Patients With Locoregional Recurrence of Squamous Cell Carcinoma of the Head and Neck (HNSCC) With No Distant Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
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
Lead sponsor: Rakuten Medical, Inc.
Sponsor class: INDUSTRY
First posted: 2024-11-21
Enrollment: 412
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Patients will be enrolled into the study starting with 3 treatment arms, ASP-1929 PIT at doses of 320 mg/m\^2 or 640 mg/m\^2 in combination with pembrolizumab treatment arms or a SOC treatment arm in which patients may receive pembrolizumab alone or pembrolizumab plus chemotherapy according to physician's choice.

Treatment assignment within the SOC treatment arm will be based on the decision of the site investigator. To ensure that the SOC treatment arm is appropriately balanced, a 50% enrollment cap will be imposed on pembrolizumab monotherapy and pembrolizumab plus chemotherapy, so that approximately the same number of patients will have been treated within each category.

At the start of the study all patients will be randomized 2:2:1 ratio to ASP-1929 PIT 320 mg/m\^2 plus pembrolizumab versus ASP-1929 PIT 640 mg/m\^2 plus pembrolizumab versus SOC (pembrolizumab alone or pembrolizumab plus chemotherapy according to physician's choice).

An interim analysis (IA) will be conducted for this study as part of the dose optimization process. Patient enrollment will continue during the period of preparation and conduct of this IA. Based on the findings from the first interim analysis (IA1), the Sponsor will have the option to close one of the two ASP-1929 PIT treatment arms for enrollment. The final decision on the optimized ASP-1929 PIT dose for this study will be made in agreement with the US Food and Drug Administration (FDA).

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Up to approximately 48 months
Secondary outcomes:
measure: Complete response rate (CRR) per modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) as assessed by central reviewer
timeFrame: Up to approximately 48 months
measure: Overall response rate (ORR) per modified RECIST 1.1 as assessed by central reviewer
timeFrame: Up to approximately 48 months
measure: Progression-free survival (PFS) per modified RECIST 1.1 as assessed by central reviewer
timeFrame: Up to approximately 48 months
measure: OS rates at 12, 18, and 24 months
timeFrame: 12, 18, and 24 months
measure: Duration of Response (DOR) per modified RECIST 1.1 as assessed by central reviewer
timeFrame: Up to approximately 48 months
measure: Duration of CR per modified RECIST 1.1 as assessed by central reviewer
timeFrame: Up to approximately 48 months
measure: Time to response (TTR)
timeFrame: Up to approximately 25 months
measure: CRR from randomization to End of Treatment as assessed by the central reviewer
timeFrame: Up to approximately 25 months
measure: Proportion of treatment-emergent adverse events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
timeFrame: Up to approximately 48 months
measure: Proportion of treatment-related adverse events (TRAEs) by CTCAE v5.0
timeFrame: Up to approximately 48 months
measure: Proportion of serious adverse events (SAEs) by CTCAE v5.0
timeFrame: Up to approximately 48 months
measure: Quality of Life assessment: EORTC Core Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30)
timeFrame: Up to approximately 28 months
measure: Quality of Life assessment: EORTC Quality of Life Questionnaire Head and Neck Module (QLQ-H&N35)
timeFrame: Up to approximately 28 months
measure: Population pharmacokinetics (PK) - Clearance (Experimental Arm Only)
timeFrame: 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
measure: Presence of anti-drug antibodies (ADAs) (Experimental Arm Only)
timeFrame: Before the start of 1st ASP-1929 infusion, 15 days after end of 1st infusion; same timepoints for 2nd ASP-1929 infusion
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: Hiroshima
country: Japan
facility: Hiroshima University
city: Kyoto
country: Japan
facility: Kyoto Prefectural University of Medicine
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Yonago
country: Japan
facility: Tottori University Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: MacKay Memorial Hospital
city: Taipei City
country: Taiwan
facility: Taipei Municipal Wanfang Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Rakuten Medical, Inc.
name: Ethan Chen, MD
role: STUDY_DIRECTOR
affiliation: Rakuten Medical, Inc.
name: Rebecca Cheng, MD
role: STUDY_DIRECTOR
References: