Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TTI-101 · 4 trials · 11 indications
Incidence of AEs, including serious AEs assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) V.5.0. Clinically significant changes between baseline and postbaseline laboratory assessments, electrocardiograms, vital signs, and physical examinations will be recorded as AEs.
* The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the dose-limiting toxicity (DLT) evaluation period. * The final determination of the RP2D will be based on an overall evaluation of the totality of the available data observed in phase IB.
An AE is any untoward medical occurrence in a participant or clinical study participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Any clinically significant changes between baseline and postbaseline laboratory assessments, electrocardiograms (ECGs), vital signs and physical examinations will be recorded as AEs.
ORR (calculated as Partial Response \[PR\] + Complete Response \[CR\]) using RECIST Version 1.1.
To determine the maximum tolerated dose (MTD), dose-limiting toxicities, and tolerability of TTI-101 administered orally to patients with advanced breast cancer and other solid tumors. Dose-limiting toxicity is defined as a Grade 3 or above adverse event (using CTCAE v5.0) within the first treatment cycle (28-days).
Cmax(obs) will be determined by direct inspection of the plasma drug concentration versus time data point values.
Tmax(obs) will also be determined by direct inspection of the plasma drug concentration versus time data point values.
AUC(0-t) (where t = the time point for the last sample on the pharmacokinetic profile in which quantifiable drug was detected) will be estimated using linear or linear/log trapezoidal calculation.
| Arm | Type | Description |
|---|---|---|
| TTI-101 400 mg/day | EXPERIMENTAL | Participants will receive 400 mg/day of TTI-101 twice daily (BID) for 12 weeks. |
| TTI-101 800 mg/day | EXPERIMENTAL | Participants will receive 800 mg/day of TTI-101 BID for 12 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive a matching placebo BID for 12 weeks. |
| TTI-101 + SBRT Dose Level 0 (original starting dose) | EXPERIMENTAL | * Treatment consists of TTI-101 by mouth twice daily at 400 mg and SBRT (5 fractions of 6.6 Gy each) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy). |
| TTI-101 + SBRT Dose Level -1 (WUSM starting dose) | EXPERIMENTAL | * Treatment consists of TTI-101 by mouth twice daily at 200 mg and SBRT (3 fractions of 6 Gy each) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy). |
| TTI-101 + SBRT Dose Level -2 | EXPERIMENTAL | * Treatment consists of TTI-101 by mouth twice daily at 200 mg and SBRT (1 fraction of 12 Gy each) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy). |
| TTI-101 + SBRT Expansion Phase | EXPERIMENTAL | * Treatment consists of TTI-101 by mouth twice daily at the RP2D dose and SBRT (at the RP2D dose and timing) over the course of 3 weeks. * After combination therapy is concluded, patients who entered the study as locally advanced will receive up to 10 additional weeks of TTI-101 monotherapy (until a tumor biopsy that will occur between Weeks 9 and 13). After discontinuation of TTI-101, patients will receive SOC chemotherapy as part of their routine care (not dictated by study participation). * Patients who entered the study as borderline resectable will be assessed following the initial 3 weeks of treatment. If they have reverted to resectable, they will undergo surgery, followed by optional adjuvant chemotherapy at the discretion of their treating team. If they are unresectable, they will follow the path of the locally advanced patients (up to 10 weeks of TTI-101 monotherapy, followed by disease assessment, followed by SOC chemotherapy). |
| Cohort A: TTI-101 as a Single Agent | EXPERIMENTAL | Cohort A Phase 1b: Participants will receive various dose levels of TTI-101 as a single agent to determine the RP2D. Cohort A Phase 2: Enrollment in Phase 2 may commence with approval from the safety review committee. Participants will be enrolled and treated at the RP2D of TTI-101 as a single agent. |
| Cohort B: TTI-101 in Combination with Pembrolizumab | EXPERIMENTAL | Cohort B Phase 1b: Participants will receive various dose levels of TTI-101 in combination with pembrolizumab to determine the RP2D. Cohort B Phase 2: Enrollment in Phase 2 may commence with approval from the safety review committee. Participants will be enrolled and treated at the RP2D of TTI-101 in combination with pembrolizumab. |
| Cohort C: TTI-101 in Combination with Atezolizumab and Bevacizumab | EXPERIMENTAL | Cohort C Phase 1b: Participants will receive various dose levels of TTI-101 in combination with atezolizumab and bevacizumab to determine the RP2D. Cohort C Phase 2: Enrollment in Phase 2 may commence with approval from the safety review committee. Participants will be enrolled and treated at the RP2D of TTI-101 in combination with atezolizumab and bevacizumab. |
| Dose escalation study | EXPERIMENTAL | Participants will receive up to 4 dose levels of TTI-101 to determine RP2D |
| Dose expansion study | EXPERIMENTAL | Enrollment in the dose expansion may commence with approval from the safety review committee. Participants will be enrolled and treated at the RP2D of TTI-101 |
| Food effect study | EXPERIMENTAL | Participants will be treated with TTI-101 at the RP2D under fed and fasted conditions to assess the bioavailability of TTI-101 and to determine the best conditions for taking the study drug |
| Dose expansion, cross-over study | EXPERIMENTAL | Participants will be administered different formulations of TTI-101 to compare bioavailability. |
| Name | Type | Description |
|---|---|---|
| TTI-101 | DRUG | Orally via a tablet. |
| Placebo | DRUG | Orally via a tablet. |
| Stereotactic body radiation therapy | RADIATION | Given at the assigned dose and fractions assigned in the protocol. |
| Pembrolizumab | DRUG | Intravenous (IV) infusion |
| Atezolizumab | DRUG | Intravenous (IV) infusion |
| Bevacizumab | DRUG | Intravenous (IV) infusion |
Inclusion Criteria: 1. Diagnosed with IPF based on either the 2018 American Thoracic Society (ATS)/ European Respiratory Society (ERS)/ Japanese Respiratory Society (JRS)/ Latin American Thoracic Association (ALAT) International Diagnostic Guidelines or on the 2022 updated guidelines within 7 years...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Bristol-Myers Squibb Company | BMY | 2 | PHASE3 | BMS-986278 |
| United Therapeutics Corporation | UTHR | 2 | PHASE3 | Treprostinil |
| AbbVie, Inc. | ABBV | 2 | PHASE2 | ABBV-142 |
| PureTech Health PLC Sponsored ADR | PRTC | 2 | PHASE3 | Deupirfenidone, Pirfenidone |
| Syndax Pharmaceuticals Inc | SNDX | 1 | PHASE2 | Axatilimab |
| Contineum Therapeutics, Inc. Class A | CTNM | 1 | PHASE2 | PIPE-791 Dose A, PIPE-791 Dose B |
| Rein Therapeutics, Inc | RNTX | 1 | PHASE2 | LTI-03 |
| Sunshine Biopharma Incorporated | SBFM | 2 | PHASE3 | HEC585, Pirfenidone |
| Cumberland Pharmaceuticals Inc. | CPIX | 1 | PHASE2 | Ifetroban |
| Avalyn Pharma Inc | AVLN | 3 | PHASE2 | AP01 |
TTI-101 is an investigational small molecule being studied for idiopathic pulmonary fibrosis, pancreatic cancer, hepatocellular carcinoma, and breast cancer. It is also being evaluated in other advanced cancers including head and neck squamous cell carcinoma, non-small cell lung cancer, colorectal cancer, gastric adenocarcinoma, and melanoma.
TTI-101 targets STAT3, a protein involved in cell signaling. By inhibiting STAT3, the drug aims to interfere with pathways that can drive tumor growth and fibrosis. It is being studied as a potential treatment across multiple oncology indications and idiopathic pulmonary fibrosis.
TTI-101 is being developed by Tvardi Therapeutics, Inc., a biopharmaceutical company. The company is conducting clinical trials of TTI-101 in the United States across multiple indications including hepatocellular carcinoma, idiopathic pulmonary fibrosis, and pancreatic cancer.
TTI-101 is in Phase 1 and Phase 2 clinical trials. It is not FDA approved and remains investigational. Studies include a completed Phase 1 trial in advanced cancers, a recruiting Phase 1 trial in hepatocellular carcinoma, a completed Phase 2 trial in idiopathic pulmonary fibrosis, and a Phase 1 trial in pancreatic cancer.
TTI-101 has been studied in several clinical trials. NCT03195699 was a completed Phase 1 trial in advanced cancers. NCT05440708 is a recruiting Phase 1 trial in hepatocellular carcinoma. NCT05671835 was a completed Phase 2 trial in idiopathic pulmonary fibrosis. NCT06141031 is a Phase 1 trial in pancreatic cancer.
TTI-101 is the primary name used for this investigational drug in clinical trials. No alternative names have been reported in the trial records. It is consistently referred to as TTI-101 across all studies listed in clinical trial registries.