Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
To review safety and efficacy of TTI-101 plus Pembrolizumab in patients the Recurrent and Metastatic head and Neck Squamous Cell Carcinoma.
Detailed description
Primary Objectives: * Objective (Phase I): Determine the phase II dose of TTI-101 when used in combination with pembrolizumab in solid tumor patients. * Objective (Phase II): Determine the overall response rate (ORR) and progression free survival (PFS) of the combination evaluated according to RECIST criteria. Secondary Objectives: * Objective: Determine the overall survival in HNSCC patients treated with the combination. * Objective: Determine the rate of immune-related severe adverse events (irSAEs) of the combination. * Objective: Evaluate the safety of the combination in solid tumor patients. Secondary Endpoint: Overall SAEs, SAEs resulting in death, discontinuation, dose reduction or dose interruption, frequency, and time to onset and severity of AEs. Exploratory Objectives: --Objective: Determine the relationship between pharmacokinetics, pharmacodynamics, baseline and post-treatment immune and tumor biomarkers and clinical responses in patients treated with the combination.
Interventions
DRUGTTI-101
Given by PO
DRUGPembrolizumab
Given by IV (vein)
Sponsors
Tvardi Therapeutics, Inc
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant Inclusion Criteria Participants are eligible to be included in the study only if all the following criteria apply: Inclusion Criteria - phase II only 1. Histologically or cytologically confirmed diagnosis of HNSCC for which no standard curative therapy is available. 2. No prior treatment with an anti-PD-1 antibody (e.g. nivolumab, pembrolizumab, cemiplimab), as well as anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. 3. Appropriate for single agent pembrolizumab. 1. Front line therapy for those whose tumors express PD L1 (CPS ≥1) OR 2. Front line therapy for those who cannot tolerate chemotherapy per the judgement of the treating physician OR 3. As second line or greater line of therapy. Inclusion Criteria - phase I only 1. Histologically or cytologically confirmed diagnosis of an invasive solid tumor malignancy, for which no standard curative or life prolonging therapy is available OR 2. Meets all inclusion criteria above for the phase II study. Inclusion Criteria - both safety and phase II 1. Male/female participants who are at least 18 years of age on the day of signing informed consent. 2. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. 3. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR 2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment. 4. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. 5. Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 21 days prior to the first dose of study intervention. 7. Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 14 days prior to the start of study intervention. 8. Able to swallow TT1-101 capsules whole.
Exclusion criteria
Participant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) | through study completion; an average of 1 year |
Outcome results
None listed