This research study is being done to assess the safety and tolerability of toripalimab in combination with cisplatin and docetaxel (PDT) induction therapy for patients with CPS-positive locally advanced head and neck squamous cell carcinoma (HNSCC).
This is a single arm phase II study to assess treatment-related adverse events (TRAEs) and efficacy of PDT. The study employs a Simon two-stage design. After 12 evaluable participants start treatment with at least 2 participants experiencing no grade 3 or higher TRAEs during induction therapy, then enrollment will continue to the target number of participants of 26. Participants will receive treatment for three cycles or until disease progression, they experience unacceptable side effects, their condition changes rendering them unacceptable for further treatment, or they withdraw from the study. Participants will be followed for two years from registration. Coherus Biosciences, Inc. is supporting this research study by providing the study drug, toripalimab, and funding for research activities. The U.S. FDA has not approved toripalimab for CPS-positive locally advanced HNSCC but has approved it for other forms of head and neck cancer. Toripalimab is a lab-made antibody that works by allowed the immune system to attack cancer cells more effectively. Toripalimab is currently sold as LOQTORZI and is used with cisplatin and gemcitabine to treat nasopharyngeal carcinoma. The U.S. FDA has approved cisplatin and docetaxel as a treatment option for multiple types of cancers, including head and neck small cell carcinoma. Cisplatin is a chemotherapy agent that works by binding to cancer cells and initiating cell death. Docetaxel is a chemotherapy agent made from a compound found in the European yew tree. Docetaxel works by stabilizing tiny structures within cancer cells, prevent cell growth and, ultimately leading to cell death. The combination of toripalimab with cisplatin and docetaxel for induction therapy is investigational.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Toripalimab-tpzi is a humanized IgG4 monoclonal antibody specific against human PD-1.
Cisplatin is an injectable chemotherapy agent classified as a platinum-based alkylating agent.
Docetaxel is a taxane chemotherapy agent.
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Proportion Grade 3-5 TRAE-free during induction therapy
Assessed using NCI Common Terminology for Adverse Event (CTCAE) version 5.0. The rate of patients with grade 3+ TRAEs-free during induction therapy will be summarized as a proportion with a corresponding exact 95% confidence interval (CI) (if the trial closes to accrual after the first stage), or a proportion with a corresponding 95% two-stage confidence interval (CI) if the trial closes to accrual after the second stage.
Time frame: Day 1 of Cycle 1 (each cycle is 21 days) to Day 10 of Cycle 3 (end of induction therapy).
Proportion Grade 3-5 TRAE-free during curative-intent treatment
Assessed using NCI Common Terminology for Adverse Event (CTCAE) version 5.0. The rate of participants grade 3+ TRAEs-free during the entire period of curative-intent treatment will be summarized as a proportion with a corresponding exact 95% confidence interval (CI) (if the trial closes to accrual after the first stage), or a proportion with a corresponding 95% two-stage confidence interval (CI) if the trial closes to accrual after the second stage.
Time frame: Day 1 of Cycle 1 (each cycle is 21 days) through the completion of 7 weeks of definitive chemoRT or 30 days after surgery for patients who undergo surgery and are deemed by the treating team to not require additional post-operative therapy.
Overall Response Rate (ORR) after PDT induction therapy
The overall response rate (ORR) will be summarized as a proportion with a corresponding exact 95% two-stage confidence interval (CI).
Time frame: Day 1 of Cycle 1 (each cycle is 21 days) to day 1 of cycle 3.
Overall Response Rate (ORR) after curative-intent therapy
The overall response rate (ORR) will be summarized as a proportion with a corresponding exact 95% two-stage confidence interval (CI).
Time frame: Day 1 of Cycle 3 (each cycle is 21 days) to day of 3-month follow-up visit.
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Event-free Survival
The Kaplan-Meier method will be used to estimate time-to-event endpoints with corresponding 95% confidence intervals (CIs) for the median or time-specific event time.
Time frame: Day 1 of Cycle 1 (each cycle is 21 days) to date of death or for up to 2 years from study registration (whichever comes first).
Overall Survival
Overall survival is the time from start of treatment to death due to any cause. The Kaplan-Meier method will be used to estimate time-to-event endpoints with corresponding 95% confidence intervals (CIs) for the median or time-specific event time.
Time frame: Day 1 of Cycle 1 (each cycle is 21 days) to date of death or for up to 2 years from study registration (whichever comes first).
Participant's Quality of Life
Patient-Reported Outcomes Measurement Information System Global 10 (PROMIS-10) Physical Health T-score and Global Mental Health T-score will be summarized descriptively via PROMIS-10 scores. The minimum score is 16 and the maximum is 68. A higher score is associated with better outcomes.
Time frame: Baseline until to 2 years from study registration.