Head and Neck Squamous Cell CarcinomaPhase 1/2NCT05668949
Phase I/II Open Label Study Evaluating the Safety and Efficacy of Combining STAT3 Inhibition (TTI-101) With Anti-PD-1 Therapy (Pembrolizumab) in Patients With Recurrent or Metastatic (RM) Head and Neck Squamous Cell Carcinoma (HNSCC)
A Phase 1/2 study testing TTI-101 and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by M.D. Anderson Cancer Center.
Trial summary
To review safety and efficacy of TTI-101 plus Pembrolizumab in patients the Recurrent and Metastatic head and Neck Squamous Cell Carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- TTI-101 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 23 Sep 2025to 23 Sep 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant Inclusion Criteria
- Participants are eligible to be included in the study only if all the following criteria apply:
- Histologically or cytologically confirmed diagnosis of HNSCC for which no standard curative therapy is available.
- 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.
- Appropriate for single agent pembrolizumab.
- Front line therapy for those whose tumors express PD L1 (CPS ≥1) OR
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- Front line therapy for those who cannot tolerate chemotherapy per the judgement of the treating physician OR
- As second line or greater line of therapy.
- Histologically or cytologically confirmed diagnosis of an invasive solid tumor malignancy, for which no standard curative or life prolonging therapy is available OR
- Meets all inclusion criteria above for the phase II study.
- Male/female participants who are at least 18 years of age on the day of signing informed consent.
- 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.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- 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.
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- 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.
- 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.
- 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.
- Able to swallow TT1-101 capsules whole.
Who cannot join
- Participant Exclusion Criteria:
- Participants are excluded from the study if any of the following criteria apply:
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to initiation of treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior systemic anti-cancer therapy including investigational agents within 3 weeks prior to initiation of treatment.
- Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline with the following exceptions: Participants with ≤ Grade 2 neuropathy are eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement are eligible.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
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- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed or mRNA vaccines is allowed.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks prior to the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in the 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, etc.) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Human Immunodeficiency Virus (HIV)-infected (HIV1/2 antibody-positive) patients may participate IF they meet all the following eligibility requirements:
- They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on this same regimen; the most recent undetectable viral load must be within the past 12 weeks.
- They must have a CD4 count ≥250 cells/mcL over the past 6 months on this same antiretroviral regimen and must not have had a CD4 count <200 cells/ mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy-induced bone marrow suppression.
- For patients who have received chemotherapy in the past 6 months, a CD4 count <250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy.
- They must have an undetectable viral load and a CD4 count ≥250 cells/mcL within 7 days of enrolment.
- They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.
- Has a known active Hepatitis B (defined as Hepatitis B RNA detected) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has had an allogenic tissue/solid organ or bone marrow transplant.
- Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association (NYHA) class III or IV, myocardial infarction within the last 12 months prior to trial entry; signs of pericardial effusion, serious arrhythmia (including QTc prolongation of >470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction <50% on screening echocardiogram.
- History of cerebral vascular accident or stroke within the previous 2 years.
- Uncontrolled hypertension (>160/100mm Hg).
- History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides).
- Previous treatment of the current malignancy with a STAT inhibitor.
About this study
To review safety and efficacy of TTI-101 plus Pembrolizumab in patients the Recurrent and Metastatic head and Neck Squamous Cell Carcinoma.
Read the 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.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- TTI-101, Pembrolizumab
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTI-101Drug
Given by PO
PembrolizumabDrug
Also called KEYTRUDA®
Given by IV (vein)
| Study group | Role | What they receive |
|---|---|---|
| Part 1 (Dose Escalation) | Experimental | Participants will be assigned to a study part based on when you join this study Receives: Drug: TTI-101; Drug: Pembrolizumab |
| Part 2 (Dose Expansion) | Experimental | Participants will be assigned to a study part based on when you join this study. Receives: Drug: TTI-101; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Measured: through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2022
- Study start23 Sep 2025
- Primary completion23 Sep 2025
- Study completion23 Sep 2025
Why it stopped: PI requested
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Tvardi Therapeutics, Inc
- Responsible party
- Sponsor
- Investigators
- Faye Johnson, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05668949
- Sponsor's protocol ID
- 2022-0625
- Other IDs
- NCI-2022-10803
- Status last verified
- Dec 2025
- First submitted
- 20 Dec 2022
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Open Label Study Evaluating the Safety and Efficacy of Combining STAT3 Inhibition (TTI-101) With Anti-PD-1 Therapy (Pembrolizumab) in Patients With Recurrent or Metastatic (RM) Head and Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT05668949
- Acronym / sponsor ID
- 2022-0625
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI requested
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Tvardi Therapeutics, Inc
- Study start
- 23 Sep 2025 (actual)
- Primary completion
- 23 Sep 2025 (actual)
- Study completion
- 23 Sep 2025 (actual)
- First posted
- 30 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 (Dose Escalation) | Experimental | Drug: TTI-101, Drug: PembrolizumabParticipants will be assigned to a study part based on when you join this study |
| Part 2 (Dose Expansion) | Experimental | Drug: TTI-101, Drug: PembrolizumabParticipants will be assigned to a study part based on when you join this study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Participant Inclusion Criteria
- Participants are eligible to be included in the study only if all the following criteria apply:
- Histologically or cytologically confirmed diagnosis of HNSCC for which no standard curative therapy is available.
- 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.
- Appropriate for single agent pembrolizumab.
Key exclusion criteria (31 listed)
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to initiation of treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior systemic anti-cancer therapy including investigational agents within 3 weeks prior to initiation of treatment.
- Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline with the following exceptions: Participants with ≤ Grade 2 neuropathy are eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement are eligible.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed or mRNA vaccines is allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TTI-101Given by PO | Drug | Part 1 (Dose Escalation), Part 2 (Dose Expansion) |
| PembrolizumabAlso: KEYTRUDA®Given by IV (vein) | Drug | Part 1 (Dose Escalation), Part 2 (Dose Expansion) |
Primary outcome
Overall Response Rate (ORR)
Time frame: through study completion; an average of 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Faye Johnson, MD principal investigator
M.D. Anderson Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TTI-101 and Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by M.D. Anderson Cancer Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.