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)

NCT05668949 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0625NCI-2022-10803
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To review safety and efficacy of TTI-101 plus Pembrolizumab in patients the Recurrent and Metastatic head and Neck Squamous Cell Carcinoma.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  through study completion; an average of 1 year

Study Arms (2)

Part 1 (Dose Escalation)

EXPERIMENTAL

Participants will be assigned to a study part based on when you join this study

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.

Drug: TTI-101; Drug: Pembrolizumab

Interventions

TTI-101 DRUG

Given by PO

Part 1 (Dose Escalation); Part 2 (Dose Expansion)

Pembrolizumab DRUG

Given by IV (vein)

Also known as: KEYTRUDA®

Part 1 (Dose Escalation); Part 2 (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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.

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Tvardi Therapeutics, Inc: collaborator

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

C188-9 compound; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Faye Johnson, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: December 30, 2022
• Study Start: September 23, 2025
• Primary Completion: September 23, 2025
• Study Completion: September 23, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12