Recurrent Head and Neck Squamous Cell Carcinoma
Conditions
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
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).
Interventions
COMBINATION_PRODUCTASP-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)
BIOLOGICALPembrolizumab
200 mg Q3W or 400 mg Q6W, IV infusion over 30 minutes (up to 24 months)
DRUGCarboplatin
Area under the curve (AUC) 5 mg/mL/min IV infusion, Q3W up to 6 cycles
DRUGCisplatin
100 mg/m\^2 IV infusion, Q3W up to 6 cycles
DRUG5-fluorouracil
1000 mg/m\^2 per day from Days 1-4 of each cycle, IV infusion, Q3W up to 6 cycles
DRUGPaclitaxel
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
DRUGDocetaxel
75 mg/m\^2 IV Infusion, Q3W up to 6 cycles
Sponsors
Rakuten Medical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to approximately 48 months | OS is defined as the time from randomization until death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 confirmed CR or confirmed 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 months | 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 confirmed response (CR or PR) |
| CRR from randomization to End of Treatment as assessed by the central reviewer | Up to approximately 25 months | CRR (confirmed response) 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 Progressive Disease \[PD\] will be counted). |
| 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 confirmed CR |
| 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, or Is a congenital anomaly/birth defect or Important medical event. |
| 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. Each scale or item score is standardized to a range of 0 to 100. Higher scores on the functional scales reflect better functioning, whereas higher scores on the symptom scales indicate more severe symptoms or greater levels of distress. Similarly, higher scores on the global health status scale denote better overall health and quality of life. Thus, an optimal quality of life profile is characterized by high scores on the functional and global health status scales, combined with low scores on the symptom scales. 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. Each scale or item score is standardized to a range of 0 to 100. Lower score on each scale represents fewer symptoms and less impact on the patient's daily life. The summed scores of the scales of EORTC-QLQ-H&N35 are compared between treatment arms. |
| Population pharmacokinetics (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. |
| 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 study treatment and any additional immune-related adverse events (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 assessed by the investigator as related to study treatment will be considered a TEAE. |
Countries
Japan, Taiwan, United States
Contacts
Primary ContactASP-1929-381 Study Team
Outcome results
None listed