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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04443088
Recruitment Status : Recruiting
First Posted : June 23, 2020
Last Update Posted : November 12, 2021
Sponsor:
Information provided by (Responsible Party):
Shenzhen Ionova Life Sciences Co., Ltd.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer Solid Tumor, Adult Cancer Metastatic Solid Carcinoma Solid Tumor, Unspecified, Adult Tumor, Solid Drug: INV-1120 Phase 1

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. Increasing doses of INV-1120 will be administered to cohorts of 3-6 participants, until the MTD or MAD is reached. 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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 26, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : March 30, 2023

Arm Intervention/treatment
Dose Escalation
Subjects will receive escalating doses of INV-1120 orally once a day until un-acceptable toxicity or disease progression. Three to six patients will be enrolled per cohort to evaluate the safety and pharmacokinetics for each dose level. After the last patient in each 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.
Drug: INV-1120
INV-1120 is an investigational selective and potent small molecule indicated for the treatment of solid malignancies including, but not limited to colorectal, breast, pancreatic, lung and liver cancers.




Primary Outcome Measures :
  1. Determine DLTs and RP2Ds in INV-1120 [ Time Frame: 12 months ]
    • 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 :
  1. Determine the PK using AUC of INV-1120 [ Time Frame: 12 months ]
    • To determine the pharmacokinetics (PK) using AUC of INV-1120 after a single dose and at steady state after multiple doses

  2. Determine the PK using Cmax of INV-1120 [ Time Frame: 12 months ]
    • To determine the pharmacokinetics (PK) using Cmax of INV-1120 after a single dose and at steady state after multiple doses

  3. Characterize investigator defined response overall response rate (ORR) using RECIST v1.1 [ Time Frame: 12 months ]
    • To characterize Investigator defined ORR using RECIST v1.1 response criteria


Other Outcome Measures:
  1. Characterize investigator defined response duration of rate (DOR) using RECIST v1.1 [ Time Frame: 12 months ]
    • To characterize investigator defined DOR as preliminary evidence of antitumor activity of INV-1120 in length of time (in days) from last study drug administration to time patient has progressive disease using RECIST v1.1.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04443088


Contacts
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Contact: Monica Mehta, PhD 1 984 710 8012 monica.mehta@syneoshealth.com

Locations
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United States, Texas
START Recruiting
San Antonio, Texas, United States, 78229
Contact: Angela Galindo       Angela.Galindo@startthecure.com   
Principal Investigator: Amita Patnaik, MD         
UT Health Recruiting
San Antonio, Texas, United States, 78229
Contact: Patricia Manea    210-450-1821    Maneap@uthscsa.edu   
Principal Investigator: John Sarantopoulos, MD         
Sponsors and Collaborators
Shenzhen Ionova Life Sciences Co., Ltd.
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Responsible Party: Shenzhen Ionova Life Sciences Co., Ltd.
ClinicalTrials.gov Identifier: NCT04443088    
Other Study ID Numbers: INV-1120-101
First Posted: June 23, 2020    Key Record Dates
Last Update Posted: November 12, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shenzhen Ionova Life Sciences Co., Ltd.:
Ionova
Ionova Bio
Cancer
Oncology
Additional relevant MeSH terms:
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Neoplasms