Digestive System Disease, Digestive System Neoplasm, Gastrointestinal Diseases, Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumors (GIST), Neoplasms, Neoplasms by Histologic Type, Neoplasms, Connective and Soft Tissue, Neoplasms, Connective Tissue
Conditions
Keywords
Gastrointestinal Stromal Tumor, GIST, KIT inhibitor, THE-630, THE630, THE 630, GIST TKI, GIST tyrosine kinase inhibitor, GIST treatments, GIST Imatinib relapse, GIST Sunitinib relapse, GIST Regorafenib relapse, GIST Ripretinib relapse, PDGFRA, KIT-mutant GIST, Advanced GIST
Brief summary
This study will assess the safety, efficacy, and pharmacokinetics of THE-630 in participants with advanced gastrointestinal stromal tumors (GIST).
Detailed description
The drug being tested in this study is called THE-630, an orally administered KIT tyrosine kinase inhibitor. The study will be conducted in two parts: a dose escalation phase, followed by an expansion phase. The patient population of the initial dose escalation phase (Phase 1) of the trial will include patients with unresectable or metastatic GIST. Patients must have disease progression on or be intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib. The primary objective of the dose escalation phase is to determine the safety profile of oral THE-630, including the dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D). Once a recommended dose has been determined in the escalation phase, the expansion phase (Phase 2) will enroll 3 cohorts of patients with unresectable or metastatic GIST defined by prior therapy: * Cohort 1: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib (≥5th Line). * Cohort 2: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting (3rd-4th Line). * Cohort 3: Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST (2nd Line). The safety and tolerability of orally administered THE-630 will continue to be assessed in the expansion cohorts. However, the primary objective of the expansion component of the trial is to evaluate the anti-tumor activity of THE-630 in these GIST patient populations.
Interventions
DRUGTHE-630
Oral THE-630 administered once daily in a continuous regimen
Sponsors
Theseus Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patient ≥18 years of age. 2. For Dose Escalation Phase Cohorts (Phase 1): 1. Have histologically- or cytologically-confirmed unresectable or metastatic GIST. 2. Have progressed on or are intolerant to imatinib therapy and have also received at least 1 of the following: sunitinib, regorafenib, ripretinib, or avapritinib. 3. For Expansion Phase Cohorts (Phase 2): 1. Cohort 1: * Have histologically- or cytologically confirmed unresectable or metastatic GIST. * Have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib. 2. Cohort 2: * Have histologically- or cytologically confirmed unresectable or metastatic GIST. * Have progressed on or are intolerant to imatinib and sunitinib. Patients in this cohort are allowed to have received up to 1 additional line of therapy in the advanced/metastatic setting. 3. Cohort 3: * Have histologically- or cytologically confirmed unresectable or metastatic GIST. * Have progressed on or are intolerant to imatinib (including in the adjuvant setting). * Have not received additional systemic therapy for advanced GIST. 4. Have at least 1 measurable lesion as defined by modified RECIST 1.1. 5. Have archival or new tumor biopsy tissue available to submit for mutational testing. Patients without appropriate archival tissue available may be discussed with the study Medical Monitor and approved for enrollment on a case-by-case basis. 6. Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. 7. Adequate renal and hepatic function as defined by the protocol. 8. Adequate bone marrow function as defined by the protocol. 9. For female patients of childbearing potential, have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test within 7 days prior to the first dose of study drug. o Note: female patients of nonchildbearing potential (postmenopausal; hysterectomy; bilateral salpingectomy; or bilateral oophorectomy) do not require a pregnancy test. 10. Female patients of childbearing potential must agree to abstain from heterosexual intercourse or use a highly effective form of contraception with their sexual partners as defined in the study protocol. Male patients with partners of childbearing potential must agree that they will abstain from heterosexual intercourse or use condoms and their partners will use highly effective contraceptive methods as defined in the study protocol. 11. All toxicities from prior therapy have resolved to Grade ≤1 according to NCI CTCAE v5.0, or have resolved to baseline, at the time of first dose of study drug. Note: treatment-related Grade \>1 alopecia, treatment related Grade 2 peripheral neuropathy, and treatment-related Grade 2 hypothyroidism on a stable dose of thyroid hormone replacement therapy are allowed if deemed irreversible. 12. Patient or legal guardian, if permitted by local regulatory authorities, signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study. 13. Willingness and ability to comply with scheduled visits and study procedures.
Exclusion criteria
1. Received systemic anticancer therapy (including cytotoxic chemotherapy, investigational agent, antineoplastic monoclonal antibodies, or immunotherapy) less than 5 half-lives or 14 days (whichever is shorter) prior to the first dose of study drug. 2. Patients known to be both KIT and PDGFRA wild-type. 3. Received radiotherapy within 14 days prior to the first dose of study drug. 4. Major surgical procedure within 28 days of the first dose of study drug. Minor surgical procedures such as central venous catheter placement or minimally invasive biopsy are allowed. 5. Have known untreated or active central nervous system metastases. 6. 12-lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's formula (QTcF) \>470 msec at screening, or history of long QTc syndrome. 7. Have significant, uncontrolled, or active cardiovascular disease, including, but not restricted to: * Myocardial infarction (MI) within 6 months prior to the first dose of study drug * Unstable angina within 6 months prior to first dose of study drug * Symptomatic congestive heart failure (New York Heart Association classes II-IV) within 6 months prior to first dose of study drug * Clinically significant, uncontrolled atrial arrhythmia (as determined by the Investigator) * Any history of ventricular arrhythmia * Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug * Uncontrolled hypertension at study entry. Patients with hypertension should be under treatment on study entry to control blood pressure. 8. Have an active uncontrolled infection, including, but not limited to, the requirement for intravenous antibiotics. 9. Patients with a known allergy or hypersensitivity to any component of the study drug. Patients with a history of Stevens-Johnson syndrome on a prior tyrosine kinase inhibitor (TKI) are excluded. 10. Any active bleeding excluding hemorrhoidal or gum bleeding. 11. For patients with a known human immunodeficiency virus (HIV) infection, have CD4+ T-cell counts \<350 cells/uL or history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months. Patients with HIV infection should be on established antiretroviral therapy (ART) for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrollment. 12. Has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as evidenced by detectable viral load (HBV-DNA or HCV-RNA, respectively). Risk of HBV reactivation should be considered in all patients and the need for anti-HBV prophylaxis should be carefully assessed. Patients with chronic HBV infection with history of active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy to be eligible for enrollment. Patients who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible. Patients on concurrent HCV treatment at the time of enrollment are allowed if HCV RNA negative. 13. Pregnant or breastfeeding. 14. Malabsorption syndrome or other illness that could affect oral absorption. 15. Patients with prior or concurrent malignancies other than GIST are allowed, except in the case where, in the opinion of the Investigator, the natural history or treatment of the other malignancy has the potential to interfere with the safety or efficacy assessment of the study drug. 16. Have any condition or illness that, in the opinion of the Investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 28 days | — |
| Dose Escalation (Phase 1): Safety Analysis - Maximum Tolerated Dose (MTD) of Orally Administered THE-630 | 28 days | The MTD is defined as the highest dose at which ≤1 of 6 DLT-assessment eligible patients experience a DLT within the first 28 days of treatment (end of Cycle 1). |
| Dose Escalation (Phase 1): Recommended Phase 2 Dose (RP2D) of Orally Administered THE-630 | 28 days | The RP2D was expected to be equal to the MTD or less than the MTD, if aspects of tolerability or efficacy not encompassed by the MTD determination suggested utilizing a lower dose. |
| Expansion (Phase 2): Efficacy Assessment - For Each Expansion Phase Cohort (Cohorts 1, 2, and 3), Confirmed Objective Response Rate (ORR), According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Up to 24 months after first dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Duration of Response (DOR), According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Progression Free Survival (PFS), According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Overall Survival (OS) | Up to 24 months after first dose | — |
| Expansion (Phase 2): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Expansion (Phase 2): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 16 weeks | — |
| Expansion (Phase 2): Efficacy Assessment - DOR, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Expansion (Phase 2): Efficacy Assessment - DCR, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Expansion (Phase 2): Efficacy Assessment - CBR at 16 Weeks, According to Modified RECIST 1.1 | 16 weeks | — |
| Expansion (Phase 2): Efficacy Assessment - PFS, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Expansion (Phase 2): Efficacy Assessment - OS | Up to 24 months after first dose | — |
| Expansion (Phase 2): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events as Assessed by NCI CTCAE v5.0 | Up to 24 months after first dose | — |
| Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | Cmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
| Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | Tmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
| Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | AUC 0-24 of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
| Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | AUC 0-t of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
| Expansion (Phase 2): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1 | Up to 24 months after first dose | — |
| Dose Escalation (Phase 1): Plasma Pharmacokinetic (PK) Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | Cmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
| Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | Tmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
| Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | AUC 0-24 of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
| Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t) | Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days) | AUC 0-t of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation (3 mg Once Daily) Patients with unresectable or metastatic GIST who received orally administered THE-630 (3 mg) once daily in a continuous regimen (28-day cycles). | 3 |
| Dose Escalation (4 mg Once Daily) Patients with unresectable or metastatic GIST who received orally administered THE-630 (4 mg) once daily in a continuous regimen (28-day cycles). | 7 |
| Dose Escalation (6 mg Once Daily) Patients with unresectable or metastatic GIST who received orally administered THE-630 (6 mg) once daily in a continuous regimen (28-day cycles). | 3 |
| Dose Escalation (9 mg Once Daily) Patients with unresectable or metastatic GIST who received orally administered THE-630 (9 mg) once daily in a continuous regimen (28-day cycles). | 3 |
| Dose Escalation (12 mg Once Daily) Patients with unresectable or metastatic GIST who received orally administered THE-630 (12 mg) once daily in a continuous regimen (28-day cycles). | 3 |
| Dose Escalation (18 mg Once Daily) Patients with unresectable or metastatic GIST who received orally administered THE-630 (18 mg) once daily in a continuous regimen (28-day cycles). | 7 |
| Dose Escalation (27 mg Once Daily) Patients with unresectable or metastatic GIST who received orally administered THE-630 (27 mg) once daily in a continuous regimen (28-day cycles). | 6 |
| Expansion Cohort 1 Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib, regorafenib and ripretinib who will receive orally administered THE-630 (once daily in a continuous regimen) at the recommended Phase 2 dose based on the dose escalation phase. | 0 |
| Expansion Cohort 2 Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib, sunitinib and 0-1 additional lines of therapy in the advanced/metastatic setting, who will receive orally administered THE-630 (once daily in a continuous regimen) at the recommended Phase 2 dose based on the dose escalation phase. | 0 |
| Expansion Cohort 3 Patients with unresectable or metastatic GIST who have progressed on or are intolerant to imatinib (including in the adjuvant setting) and who have not received additional systemic therapy for advanced GIST, who will receive orally administered THE-630 (once daily in a continuous regimen) at the recommended Phase 2 dose based on the dose escalation phase. | 0 |
| Total | 32 |
Baseline characteristics
| Characteristic | Dose Escalation (4 mg Once Daily) | Dose Escalation (6 mg Once Daily) | Dose Escalation (9 mg Once Daily) | Dose Escalation (12 mg Once Daily) | Dose Escalation (18 mg Once Daily) | Dose Escalation (27 mg Once Daily) | Dose Escalation (3 mg Once Daily) | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 2 Participants | 20 Participants |
| Age, Continuous | 57.7 years STANDARD_DEVIATION 10.66 | 57.7 years STANDARD_DEVIATION 15.04 | 49.0 years STANDARD_DEVIATION 6 | 62.7 years STANDARD_DEVIATION 9.29 | 64.6 years STANDARD_DEVIATION 9.07 | 60.8 years STANDARD_DEVIATION 18.32 | 56.3 years STANDARD_DEVIATION 13.01 | 59.3 years STANDARD_DEVIATION 12.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 2 Participants | 3 Participants | 3 Participants | 7 Participants | 5 Participants | 3 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 3 Participants | 2 Participants | 6 Participants | 6 Participants | 3 Participants | 29 Participants |
| Region of Enrollment United States | 7 participants | 3 participants | 3 participants | 3 participants | 7 participants | 6 participants | 3 participants | 32 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 4 Participants | 1 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 6 / 7 | 2 / 3 | 0 / 3 | 1 / 3 | 2 / 7 | 1 / 6 |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 3 / 3 | 3 / 3 | 3 / 3 | 7 / 7 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 5 / 7 | 1 / 3 | 0 / 3 | 1 / 3 | 5 / 7 | 1 / 6 |
Outcome results
Primary
Dose Escalation (Phase 1): Recommended Phase 2 Dose (RP2D) of Orally Administered THE-630
The RP2D was expected to be equal to the MTD or less than the MTD, if aspects of tolerability or efficacy not encompassed by the MTD determination suggested utilizing a lower dose.
Time frame: 28 days
Population: DLT-Evaluable Analysis Set (Phase 1 only), which includes patients enrolled in the Dose Escalation (Phase 1) portion who completed at least 75% of the planned total dose during Cycle 1 (DLT evaluation period, i.e. 21 of 28 days) and patients who experienced a protocol-defined DLT, regardless of dosing adherence in Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Recommended Phase 2 Dose (RP2D) of Orally Administered THE-630 | NA mg |
Primary
Dose Escalation (Phase 1): Safety Analysis - Maximum Tolerated Dose (MTD) of Orally Administered THE-630
The MTD is defined as the highest dose at which ≤1 of 6 DLT-assessment eligible patients experience a DLT within the first 28 days of treatment (end of Cycle 1).
Time frame: 28 days
Population: DLT-Evaluable Analysis Set (Phase 1 only), which includes patients enrolled in the Dose Escalation (Phase 1) portion who completed at least 75% of the planned total dose during Cycle 1 (DLT evaluation period, i.e. 21 of 28 days) and patients who experienced a protocol-defined DLT, regardless of dosing adherence in Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Maximum Tolerated Dose (MTD) of Orally Administered THE-630 | NA mg |
Primary
Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630
Time frame: 28 days
Population: DLT-Evaluable Analysis Set (Phase 1 only), which includes patients enrolled in the Dose Escalation (Phase 1) portion who completed at least 75% of the planned total dose during Cycle 1 (DLT evaluation period, i.e. 21 of 28 days) and patients who experienced a protocol-defined DLT, regardless of dosing adherence in Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 0 Participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 1 Participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 0 Participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 0 Participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 0 Participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 0 Participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Dose-limiting Toxicities (DLTs) Following Oral Administration of THE-630 | 2 Participants |
Primary
Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: Up to 24 months after first dose
Population: Full Analysis Set, which includes all patients who were enrolled and received at least 1 dose of THE-630.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 3 Participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 7 Participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 3 Participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 3 Participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 3 Participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 7 Participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 | 6 Participants |
Primary
Expansion (Phase 2): Efficacy Assessment - For Each Expansion Phase Cohort (Cohorts 1, 2, and 3), Confirmed Objective Response Rate (ORR), According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: Up to 24 months after first dose
Population: The Sponsor terminated the study due to early dose-limiting toxicities and not initiate Expansion Cohort 1, Expansion Cohort 2 or Expansion Cohort 3 (Phase 2).
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: Full Analysis Set, which includes all patients who were enrolled and received at least 1 dose of THE-630.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Stable Disease (SD) | 0 Participants |
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Complete Response (CR) | 0 Participants |
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Not Evaluable (NE) | 0 Participants |
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Parital Response (PR) | 0 Participants |
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Progressive Disease (PD) | 3 Participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Stable Disease (SD) | 1 Participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Parital Response (PR) | 0 Participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Progressive Disease (PD) | 3 Participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Complete Response (CR) | 0 Participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Not Evaluable (NE) | 3 Participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Not Evaluable (NE) | 0 Participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Parital Response (PR) | 0 Participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Complete Response (CR) | 0 Participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Stable Disease (SD) | 1 Participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Progressive Disease (PD) | 2 Participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Stable Disease (SD) | 3 Participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Complete Response (CR) | 0 Participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Parital Response (PR) | 0 Participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Progressive Disease (PD) | 0 Participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Not Evaluable (NE) | 0 Participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Complete Response (CR) | 0 Participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Not Evaluable (NE) | 0 Participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Stable Disease (SD) | 3 Participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Progressive Disease (PD) | 0 Participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Parital Response (PR) | 0 Participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Complete Response (CR) | 0 Participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Not Evaluable (NE) | 1 Participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Progressive Disease (PD) | 3 Participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Parital Response (PR) | 0 Participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Stable Disease (SD) | 3 Participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Progressive Disease (PD) | 2 Participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Parital Response (PR) | 0 Participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Stable Disease (SD) | 4 Participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Complete Response (CR) | 0 Participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1 | Not Evaluable (NE) | 0 Participants |
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1
Time frame: 16 weeks
Population: Full Analysis Set, which includes all patients who were enrolled and received at least 1 dose of THE-630.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 14.3 percentage of participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 66.7 percentage of participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 66.7 percentage of participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 14.3 percentage of participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Clinical Benefit Rate (CBR) at 16 Weeks, According to Modified RECIST 1.1 | 50.0 percentage of participants |
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: Full Analysis Set, which includes all patients who were enrolled and received at least 1 dose of THE-630.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Confirmed ORR, According to Modified RECIST 1.1 | 0 percentage of participants |
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: Full Analysis Set, which includes all patients who were enrolled and received at least 1 dose of THE-630.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation (3 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | 0 percentage of participants |
| Dose Escalation (4 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | 14.3 percentage of participants |
| Dose Escalation (6 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | 33.3 percentage of participants |
| Dose Escalation (9 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | 100 percentage of participants |
| Dose Escalation (12 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | 100 percentage of participants |
| Dose Escalation (18 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | 42.9 percentage of participants |
| Dose Escalation (27 mg Once Daily) | Dose Escalation (Phase 1): Efficacy Assessment - Disease Control Rate (DCR), According to Modified RECIST 1.1 | 66.7 percentage of participants |
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Duration of Response (DOR), According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Overall Survival (OS)
Time frame: Up to 24 months after first dose
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Progression Free Survival (PFS), According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Plasma Pharmacokinetic (PK) Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration)
Cmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: The scope of planned analyses and data reporting was reduced (per statistical analysis plan \[SAP\] v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours)
AUC 0-24 of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t)
AUC 0-t of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Dose Escalation (Phase 1): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax)
Tmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: The scope of planned analyses and data reporting was reduced (per SAP v3.0), given the Sponsor's decision to terminate the study early due to dose-limiting toxicities and to discontinue the THE-630 development program. As a result, data for this outcome measure are not available.
Secondary
Expansion (Phase 2): Efficacy Assessment - Best Overall Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Efficacy Assessment - Best Target Lesion Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Efficacy Assessment - CBR at 16 Weeks, According to Modified RECIST 1.1
Time frame: 16 weeks
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Efficacy Assessment - DCR, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Efficacy Assessment - DOR, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Efficacy Assessment - OS
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Efficacy Assessment - PFS, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Efficacy Assessment - Time to Response, According to Modified RECIST 1.1
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-24 (Area Under the Concentration-time Curve From Time Zero to 24 Hours)
AUC 0-24 of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - AUC 0-t (Area Under the Concentration-time Curve From Time Zero to Time t)
AUC 0-t of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Cmax (Maximum Observed Concentration)
Cmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Plasma PK Parameters of THE-630 and Its Active Metabolite - Tmax (Time of First Occurrence of Cmax)
Tmax of THE-630 and its active metabolite after single oral dose and at steady state after multiple oral doses
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 28 days)
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.
Secondary
Expansion (Phase 2): Safety Analysis - Number of Participants With Treatment-emergent Adverse Events as Assessed by NCI CTCAE v5.0
Time frame: Up to 24 months after first dose
Population: No patients were enrolled in the Expansion cohorts, as the study was terminated by the Sponsor due to dose-limiting toxicities prior to initiation of the Expansion phase (Phase 2) of the study.