A Phase Ib/II, Multicenter, Open-Label Study of TT-00420 Tablet, as Monotherapy or in Combination Regimens, in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- TT-00420
- Conditions
- Advanced Solid Tumor
- Sponsor
- TransThera Sciences (Nanjing), Inc.
- Enrollment
- 203
- Locations
- 6
- Primary Endpoint
- Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.).
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥ 18 years of age
- •Histopathological or cytologically documented locally advanced or metastatic solid tumors who have no available standard therapeutic treatment options
- •At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:
- •Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
- •Hemoglobin (Hgb) ≥ 8 g/dl
- •Platelets (plt) ≥ 75 x 10\^9/L
- •AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present
- •Total bilirubin ≤ 1.5 x ULN
Exclusion Criteria
- •Women who are pregnant or lactating
- •Women of child-bearing potential (WOCBP) who do not use adequate birth control
- •Patients with any hematologic malignancy, including leukemia (any form), lymphoma, and multiple myeloma
- •Patients with a history of primary central nervous system tumors or carcinomatous meningitis.
- •Patients with the following mood disorders as judged by the Investigator or a psychiatrist:
- •Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia; a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
- •≥ CTCAE grade 3 anxiety
- •Impaired cardiac function or significant diseases, including but not limited to any of the following:
- •left ventricular ejection fraction (LVEF) \< 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
- •Congenital long QT syndrome
Arms & Interventions
Monotherapy Cohorts
TT-00420 tablets will be administered once daily in 28-day cycles.
Intervention: TT-00420
Dose Escalation Cohorts (Combination Therapy)
TT-00420 tablets will be administered once daily in 28-day cycles. Nab-paclitaxel 100 mg/m\^2 will be administered intravenously on Day 1, 8, and 15 of each 28-day cycle. Dose escalation will be guided by a 3+3 design in Phase Ib to determine the recommended phase 2 dose (RP2D).
Intervention: TT-00420
Dose Escalation Cohorts (Combination Therapy)
TT-00420 tablets will be administered once daily in 28-day cycles. Nab-paclitaxel 100 mg/m\^2 will be administered intravenously on Day 1, 8, and 15 of each 28-day cycle. Dose escalation will be guided by a 3+3 design in Phase Ib to determine the recommended phase 2 dose (RP2D).
Intervention: Nab-Paclitaxel
PK Run-in Cohorts
TT-00420 tablets will be administered once or twice daily in 28-day cycles according to assigned cohort.
Intervention: TT-00420
Outcomes
Primary Outcomes
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time Frame: Up to 30 days from study discontinuation
As assessed per NCI Common Toxicity Criteria for Adverse Events, version 5.0
Dose limiting toxicity (DLT)
Time Frame: Up to 28 days from the first dose
Dose escalation cohorts are monitored and assessed using the NCI Common Toxicity Criteria for Adverse Events, version 5.0.
Secondary Outcomes
- Time to Maximum Concentration (Tmax)(From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days))
- Duration of Objective Response (DOR)(Through study completion, an average of 9 months.)
- Overall Survival (OS)(From first study drug administration until the date of death from any cause, assessed up to 24 months)
- Area under the curve (AUC0-t)(From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days))
- Maximum observed concentration (Cmax)(From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days))
- Half-life (T1/2)(From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days))
- Objective Response Rate (ORR)(Through study completion, an average of 9 months.)
- Area under the curve (AUC0-∞)(From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days))
- Disease Control Rate (DCR)(Through study completion, an average of 9 months.)
- Progression Free Survival (PFS)(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)
- Volume of Distribution (Vd)(From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle is 28 days))