This is a Phase Ib/II, multicenter, open-label study to evaluate the safety and preliminary efficacy of TT-00420 tablet, as monotherapy or in combination regimens, in patients with advanced solid tumors.
Study consists of three arms, Arm A is a Phase Ib/II study of TT-00420 tablet monotherapy, Arm B is a Phase Ib/II study of TT-00420 tablet in combination with nab-paclitaxel (Abraxane®) and Arm C is a PK run-in study of TT-00420 tablet. Arm A: TT-00420 Tablet Monotherapy Phase Ib will enroll patients with preferred indications including metastatic cholangiocarcinoma, HER2-negative breast cancer including TNBC, bladder cancer, small cell lung cancer, prostate cancer, thyroid cancer, sarcoma, gastric cancer, gallbladder cancer and other advanced solid tumors to receive TT-00420 monotherapy. Based on preliminary efficacy results, Phase II will enroll additional patients in select indications to evaluate the efficacy of TT-00420 monotherapy. Arm B: TT-00420 tablet in combination with nab-paclitaxel (Abraxane®) Arm B will enroll patients with metastatic HER2-negative breast cancers, including triple-negative breast cancer (TNBC). Phase Ib will be a dose escalation study of TT-00420 in combination with nab-paclitaxel, guided by 3+3 design, to determine a Recommended Phase 2 Dose (RP2D). Phase II will enroll additional patients with metastatic HER2-negative breast cancers to further evaluate the efficacy of the combination regimen. Arm C: PK Run-in Study of TT-00420 Tablet Arm C will enroll patients with preferred indications including cholangiocarcinoma, TNBC/HER2- negative breast cancer, prostate cancer, sarcoma, hepatocellular carcinoma (HCC), bladder cancer, small cell lung cancer, thyroid cancer, gastric cancer, gallbladder cancer and other advanced solid tumors to receive TT-00420 monotherapy administered as once daily (q.d.) or twice daily (b.i.d.).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
203
TT-00420 tablet will be administered orally once daily per protocol defined schedule.
Nab-Paclitaxel would be administered via infusion on Day 1,8, and 15 of 28-day cycle
City of Hope
Duarte, California, United States
The University of Chicago
Chicago, Illinois, United States
Rutgers Cancer Institute
New Brunswick, New Jersey, United States
Gabrail Cancer Center Research
Canton, Ohio, United States
UT Southwestern Medical Center
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
As assessed per NCI Common Toxicity Criteria for Adverse Events, version 5.0
Time frame: Up to 30 days from study discontinuation
Dose limiting toxicity (DLT)
Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.
Time frame: Up to 28 days from the first dose
Objective Response Rate (ORR)
The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.
Time frame: Through study completion, an average of 9 months.
Disease Control Rate (DCR)
Defined as CR + PR + stable disease (SD) based on RECIST version 1.1.
Time frame: Through study completion, an average of 9 months.
Duration of Objective Response (DOR)
Duration of response for CR or PR based on RECIST version 1.1.
Time frame: Through study completion, an average of 9 months.
Progression Free Survival (PFS)
Time frame: From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall Survival (OS)
Time frame: From first study drug administration until the date of death from any cause, assessed up to 24 months
Area under the curve (AUC0-∞)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Area under the curve (AUC0-t)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Maximum observed concentration (Cmax)
Blood samples will be collected at designated time points for pharmacokinetic analysis of TT-00420 and/or nab-paclitaxel.
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Half-life (T1/2)
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Time to Maximum Concentration (Tmax)
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
Volume of Distribution (Vd)
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days)
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