Clinical Trials /

A Phase 1, Multi-Center, Safety, Dose Escalation, Pharmacokinetics of INV-1120 in Adult Patients Advanced Solid Tumors

NCT04443088

Description:

Phase 1, first-in-human, open-label dose-escalation study to determine the MTD and RP2D, and to assess the DLT of INV-1120 (also referred to as investigational product or IP). The safety, tolerability, and PK of INV-1120 will be assessed in adult patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1, Multi-Center, Safety, Dose Escalation, Pharmacokinetics of INV-1120 in Adult Patients Advanced Solid Tumors
  • Official Title: A Phase 1, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Evidence of Antitumor Activity of INV-1120 as a Single Agent in Adult Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: INV-1120-101
  • NCT ID: NCT04443088

Conditions

  • Cancer
  • Solid Tumor, Adult
  • Cancer Metastatic
  • Solid Carcinoma
  • Solid Tumor, Unspecified, Adult
  • Tumor, Solid

Interventions

DrugSynonymsArms
INV-1120Dose Escalation

Purpose

Phase 1, first-in-human, open-label dose-escalation study to determine the MTD and RP2D, and to assess the DLT of INV-1120 (also referred to as investigational product or IP). The safety, tolerability, and PK of INV-1120 will be assessed in adult patients with advanced solid tumors. The total number of patients enrolled in the study will depend upon the number of dose-escalation cohorts. It is estimated that approximately 36 evaluable patients will be enrolled in the dose-escalation part of this study. This multicenter study will be conducted in the United States.

Detailed Description

      Phase 1, open-label dose-escalation study to determine the MTD and RP2D, and to assess the
      DLT of INV-1120 (also referred to as investigational product or IP). The safety,
      tolerability, and PK of INV-1120 will be assessed in adult patients with advanced solid
      tumors. The total number of patients enrolled in the study will depend upon the number of
      dose-escalation cohorts.

      Three to six new patients will be enrolled per cohort to evaluate the safety and
      pharmacokinetics for each dose level. Dose will be escalated according to the 3+3 scheme. If
      none of the first 3 treated patients experiences any DLT, dose escalation may proceed with a
      new cohort at the next higher dose level. If 1 out of the first 3 patients experiences any
      DLT, up to 3 additional patients will be enrolled and treated at that dose level for safety
      evaluation. Under these circumstances, all 6 patients must complete the first cycle of
      treatment and if there is no occurrence of DLT in a second patient, ie, <33% of patients have
      experienced DLT, then further dose escalation may proceed. If 2 or more DLTs occur at any
      time, or if the DLT rate equals or exceeds 33% at a given dose level during Cycle 1, then it
      is considered that the MTD has been exceeded. Once the MTD level has been exceeded, dose
      escalation will be stopped, and no further patients will be enrolled at that dose level. In
      the instance that MTD is exceeded, then 3 more patients should be enrolled, if not already
      done so, at the next lower dose level, resulting in a total of at least 6 patients treated
      for the safety evaluation. The MTD is defined as the highest dose level at which at least 6
      patients have been treated and less than 33% of patients experienced the DLT.

      For every dose level, after all patients in each cohort complete Cycle 1 (DLT observation
      period), a safety team will evaluate the data for DLT determination and decide whether to
      escalate the next higher dose level.

      The MTD will generally be considered as the RP2D. However, the RP2D may also be determined
      based on the data of pharmacokinetics, pharmacodynamic biomarkers in blood and the
      preliminary clinical activity of INV-1120, as well as the incidence rate and nature of the
      toxicities observed in subsequent cycles beyond Cycle 1.

      INV-1120 will be administered once daily (QD) orally (PO). For the purposes of this study,
      treatment cycles will be 28 days or 4 weeks. INV-1120 will be administered orally to
      patients. Patients will undergo safety assessment every 7 days in Cycle 1 and Cycle 2; every
      14 days during Cycle 3 and Cycle 4, patients will undergo safety assessment every 14 days;
      from Cycle 5 and beyond, patient will undergo one safety assessment every cycle. Additional
      assessments may be done as clinically indicated.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationOtherDose escalation with a starting dose at 15 mg once daily (QD) will consist of dose levels of 15, 30, 60, 100, 150, 200, 250 and 300 mg QD (see Table 2). Three to six patients will be enrolled per cohort to evaluate the safety and pharmacokinetics for each dose level. After the last patient in the first cohort completes Cycle 1 (DLT observation period of 28 days), the Safety Evaluation Team (SET) will evaluate the safety data and pharmacokinetic collected from Cycle 1, and make the decision whether to escalate the dose before opening the second cohort.
  • INV-1120

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent, according to local guidelines, signed and dated by the
             patient prior to the performance of any study-specific procedures, sampling, or
             analyses;

          2. Patient must be ≥18 years-of-age at the time of signature of the informed consent form
             (ICF);

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1;

          4. Patients with histologically or cytologically confirmed advanced solid tumors which
             have progressed on or following standard therapy or for which no standard therapy
             exists;

          5. Patients with life expectancy ≥3 months;

          6. Patients with at least one measurable lesion by computed tomography (CT) or magnetic
             resonance imaging (MRI), according to RECIST v1.1. Tumor lesions that have been
             irradiated ≥4 weeks before the start of treatment, and have subsequently had
             documented progression, may be chosen as target lesions in the absence of measurable
             lesions that have not been irradiated;

          7. Patients whose laboratory data at screening meet the acceptable criteria for bone
             marrow, liver function and renal function.

          8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
             (urinary or serum beta human chorionic gonadotropin [β-hCG]) during screening. A woman
             is considered of childbearing potential (fertile) following menarche and until
             becoming postmenopausal unless permanently sterile. A postmenopausal state is defined
             as no menses for 12 months without an alternative medical cause. Postmenopausal women
             can be included;

          9. Male patients with female partners of childbearing potential and female patients of
             childbearing potential are required to use two forms of acceptable contraception,
             including one barrier method, during their participation in the study and for 3 months
             following last dose. Medically acceptable contraception includes:

               -  Hormonal methods (Needs to have been instituted at least 1 month prior to the
                  first dose of study drug):

               -  Barrier methods:

               -  Abstinence, defined as refraining from sexual intercourse

         10. Male patients must also refrain from donating sperm from the first dose of study drug
             until 3 months after the last dose of study drug;

         11. Patients must be able to swallow and retain orally administered medication.

        Exclusion Criteria:

          1. History (≤5 years) or current evidence of cancer that is histologically distinct from
             the cancer under study, except for cervical carcinoma in situ, superficial
             non-invasive bladder tumors, or curatively treated Stage I non-melanoma skin cancer;

          2. Known serious allergy to investigational drug or excipients (microcrystalline
             cellulose);

          3. History of severe autoimmune disease (including significant ongoing immune-related
             adverse events of prior immune-oncology therapy) or autoimmune disorder that requires
             chronic systemic corticosteroid treatment at immunosuppressive doses (prednisone >10
             mg/day or equivalent);

          4. Known malignant central nervous system disease other than neurologically stable,
             treated brain metastases - defined as metastases having been treated by surgery,
             surgery plus radiotherapy or radiotherapy alone, with no evidence of progression or
             hemorrhage and off any systemic corticosteroids for at least 4 weeks prior to signing
             the consent;

          5. History (within 4 weeks of starting treatment) or evidence of active infections (Grade
             ≥2);

          6. History of seropositive status for human immunodeficiency virus (HIV), hepatitis B
             virus (HBV), or hepatitis C virus (HCV) at any time before the start of treatment:
             Testing for seropositive status during screening will be at the discretion of the
             Investigator in patients without previously reported results;

          7. History or evidence of any severe and/or uncontrolled medical conditions or other
             conditions that, in the opinion of the Investigator and Sponsor, could affect the
             patient's participation in the study, such as any disorder or surgical procedure that
             could impact the absorption of study drug from the gastrointestinal tract.

          8. History (≤6 months before the start of treatment) or evidence of any of the following:
             acute myocardial infarction, unstable angina pectoris, coronary artery bypass graft,
             cerebrovascular accident, or transient ischemic attack;

          9. Patients who have impaired cardiac function or clinically significant cardiac
             diseases, including any of the following:

               -  Congenital long QT syndrome;

               -  Significant ventricular or supraventricular arrhythmias (patients with sinus
                  arrhythmia or chronic rate-controlled atrial fibrillation in the absence of other
                  cardiac abnormalities are eligible);

               -  LVEF < 50% by ECHO or MUGA;

               -  Other clinically significant heart disease such as known congestive heart failure
                  New York Heart Association (NYHA) Class III-IV;

         10. Patients with QT interval ≥470 msec in females and ≥450 msec in males at screening
             using Fridericia's formula (determined as the mean of 3 QTcF values from the screening
             triplicate ECG obtained with adequate quality);

         11. Women who are pregnant or breastfeeding.

         12. WOCBP and sexually active fertile men with WOCBP partners who are unwilling or unable
             to use acceptable contraception method to avoid pregnancy for at least 1 month before
             the first dose of the study drug, during the study, and for 3 months after the last
             dose of study drug;

         13. Male patient who plans to father a child while enrolled in this study or within 3
             months after the last dose of study drug;

         14. Not recovered from toxicity from prior anticancer therapy to baseline or Grade 1
             (except toxicities which are not clinically significant such as alopecia, skin
             discoloration).

         15. History of an allogeneic bone marrow or solid organ transplant;

         16. Use of systemic anti-cancer agent (except luteinizing hormone-releasing hormone (LHRH)
             agonists, bisphosphonates and denosumab) or investigational drug ≤28 days or five
             half-lives whichever is longer prior to the first dose of INV-1120;

         17. Radiation therapy ≤28 days prior to the first dose of INV-1120, or likely to require
             radiation therapy at any time until the 30 days after the last dose of INV-1120,
             except for palliative radiation therapy limited to non-target bone lesions;

         18. Major surgery within 4 weeks before enrollment or surgery with ongoing post-operative
             complications);

         19. History of transfusion of platelets ≤2 weeks before the start of treatment;

         20. Patients who start erythropoietin or granulocyte-colony stimulating factor (G-CSF),
             pegfilgrastim, or filgrastim ≤2 weeks before start of treatment;

         21. Patients taking medications known to have a significant risk of causing Torsades de
             Pointes. Patients who have discontinued any of these medications must have a wash-out
             period of at least 7 days or at least 5 half-lives of the drug (whichever is longer)
             prior to the first dose of study drug.

         22. History of use of H2 blockers (<24 hours before the first dose of INV-1120 and during
             the study) and proton pump inhibitors (<5 days before the first dose of INV-1120 and
             during the study).

         23. Patients with recent (< 6 months) history, or are currently being treated for
             gastroesophageal ulcer
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine DLTs and RP2Ds in INV-1120
Time Frame:12 months
Safety Issue:
Description:• To evaluate dose limiting toxicities (DLTs) of INV-1120 in patients with advanced cancer and to establish a recommended Phase 2 dose (RP2D)

Secondary Outcome Measures

Measure:Determine the PK using AUC of INV-1120
Time Frame:12 months
Safety Issue:
Description:• To determine the pharmacokinetics (PK) using AUC of INV-1120 after a single dose and at steady state after multiple doses
Measure:Determine the PK using Cmax of INV-1120
Time Frame:12 months
Safety Issue:
Description:• To determine the pharmacokinetics (PK) using Cmax of INV-1120 after a single dose and at steady state after multiple doses
Measure:Characterize investigator defined response overall response rate (ORR) using RECIST v1.1
Time Frame:12 months
Safety Issue:
Description:• To characterize Investigator defined ORR using RECIST v1.1 response criteria

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shenzhen Ionova Life Sciences Co., Ltd.

Trial Keywords

  • Ionova
  • Ionova Bio
  • Cancer
  • Oncology

Last Updated

June 19, 2020