TTI-101 for Head and Neck Cancer

Overseen By Andrew Sikora, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antibiotics, Immunosuppressants

Disqualifiers: Pregnancy, Active infections, Cardiac issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TTI-101 (also known as C-188-9) to determine if it can slow the growth of certain head and neck cancers not linked to HPV, a common virus. The treatment is administered before surgery to assess its potential to enhance surgical effectiveness. Individuals with stage II-IV HPV-negative squamous cell carcinoma of the head and neck who plan to undergo surgery might be suitable candidates. Participants will be randomly assigned to receive either TTI-101 or join a control group for comparison. As an Early Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but certain medications like systemic immunosuppressive drugs and recent investigational agents are not allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TTI-101 has been tested in several studies, demonstrating promising safety results. Earlier research found that TTI-101 stopped the growth of various cancers, including head and neck cancers, in animals like mice, without causing harm, suggesting it is well-tolerated.

Further studies with humans have shown that TTI-101 did not cause any major harmful effects. For instance, a study with patients who had solid tumors found that TTI-101 was safe and did not lead to significant side effects. Additionally, the treatment showed meaningful antitumor activity, which is encouraging for its potential use in cancer treatment.

This trial is in its early stages, focusing mainly on assessing safety and determining the best dosage. While early results are promising, ongoing trials are essential to fully understand the safety of TTI-101 in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for head and neck cancer, such as surgery, radiation, and chemotherapy, TTI-101 targets a specific protein involved in cancer cell growth known as STAT3. This protein plays a crucial role in the survival and proliferation of cancer cells, and by inhibiting it, TTI-101 aims to stop the cancer from growing and spreading. Researchers are excited about TTI-101 because it offers a more targeted approach, potentially leading to fewer side effects and improved outcomes compared to broader, more aggressive treatments.

What evidence suggests that TTI-101 might be an effective treatment for head and neck cancer?

Research shows that TTI-101, a new pill, targets a protein called STAT3, which is often active in many cancers, including head and neck cancer. Studies have found that TTI-101 can stop these cancers from growing in mice. Tests on people with different types of tumors showed promising results, such as partial tumor shrinkage. Additionally, TTI-101 was well-tolerated, causing no severe side effects in early tests. In this trial, participants will be randomly assigned to receive either TTI-101 or be part of a control group receiving standard care. These findings suggest that TTI-101 might help reduce the growth of head and neck cancer, especially before surgery. ^{3 4 6 7 8}

Who Is on the Research Team?

Andrew Sikora, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Stage II-IV HPV-negative squamous cell carcinoma of the head and neck, who can swallow pills, have no distant metastases, and are planning surgery as primary therapy. Participants must not be pregnant or breastfeeding and agree to use contraception. They should have adequate organ function and no recent vaccines or major surgeries.

Inclusion Criteria

My cancer is a stage II-IV squamous cell carcinoma of the head or neck.

My oropharyngeal cancer is not linked to HPV.

I am scheduled for surgery to remove my cancer, possibly followed by radiation.

Exclusion Criteria

My high blood pressure is not under control.

I have not had signs of infection in the last 2 weeks.

I have not had severe infections in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgical Treatment

Participants receive TTI-101 to assess its effect on tumor growth before standard of care surgery

4-6 weeks

Surgery

Participants undergo standard of care surgery with or without radiation

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after treatment and surgery

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Control Group
• TTI-101

Trial Overview The study tests TTI-101's effectiveness in reducing tumor growth before standard surgery compared to a control group receiving no TTI-101. It's a randomized trial where patients are assigned by chance to either receive TTI-101 or be in the control group prior to their planned surgical treatment.

How Is the Trial Designed?

Group I: TTI-101 Experimental Treatment 1 Intervention

Participants you will be randomly assigned to either receive the study drug or be in a control group.

Group II: Control Group Experimental Treatment 1 Intervention

Participants you will be randomly assigned to either receive the study drug or be in a control group.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Tvardi Therapeutics, Inc

Collaborator

Trials

2

Recruited

80+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11911802/

Phase I Trial of TTI-101, a First-in-Class Oral Inhibitor of ... We conducted a phase I study of TTI-101, a first-in-class, selective small-molecule inhibitor of signal transducer and activator of transcription 3, in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03195699

NCT03195699 | Oral STAT3 Inhibitor, TTI-101, in Patients ... Administration of TTI-101 to mice demonstrated that it blocked growth of cancers of the breast, head and neck, lung, and liver and it was safe when administered ...

3. onclive.com onclive.com/view/novel-stat3-inhibitor-tt1-101-is-safe-and-shows-antitumor-activity-in-r-r-hcc-and-other-solid-tumors

Novel STAT3 Inhibitor TT1-101 Is Safe and Shows ... Treatment with TT1-101, was well tolerated and showed clinically meaningful antitumor activity, including confirmed partial responses (cPRs) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5041982/

Small-molecule inhibition of STAT3 in radioresistant head ... STAT3 activity is increased in ~50% of all cancers [10], due, in many instances, to activation of signaling molecules upstream of STAT3, including receptor ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006295221003014

TTI-101: A competitive inhibitor of STAT3 that spares ... In fact, TTI-101 administration unexpectedly reversed mechanical allodynia in models of chemotherapy-induced peripheral neuropathy (CIPN) and spared nerve ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10803

TTI-101 and Pembrolizumab in Treating Patients with ... This phase I/II trial tests the safety, side effects, and best dose of STAT3 Inhibitor C-188-9 (TTI-101) and pembrolizumab for treating patients with head and ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/31/6/965/753254/Phase-I-Trial-of-TTI-101-a-First-in-Class-Oral

Phase I Trial of TTI-101, a First-in-Class Oral Inhibitor of ... The antitumor activity of TTI-101 monotherapy in patients with advanced, metastatic solid tumors is promising. A phase II study of TTI-101 in hepatocellular ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8478865/

TTI-101: A competitive inhibitor of STAT3 that spares ... TTI-101 has shown target engagement, no toxicity, and evidence of clinical benefit in a Phase I study in patients with solid tumors. Here we report that TTI-101 ...