Clinical Trials /

A Study of IMMH-010 in Patients With Advanced Malignant Solid Tumors

NCT04343859

Description:

Phase I study of IMMH-010 in patients with advanced malignant solid tumors

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of IMMH-010 in Patients With Advanced Malignant Solid Tumors
  • Official Title: A Phase I Clinical Trial of IMMH-010 in Patients With Advanced Malignant Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: HR-IMMH001
  • NCT ID: NCT04343859

Conditions

  • Malignant Neoplasms

Interventions

DrugSynonymsArms
IMMH-010IMMH-010-120mg

Purpose

Phase I study of IMMH-010 in patients with advanced malignant solid tumors

Detailed Description

      To evaluate the safety and tolerance of single and multiple doses of IMMH-010 in patients
      with advanced solid tumors; To determine the maximum-tolerated dose (MTD) and recommended
      Phase II dose (RP2D) of IMMH-010; To evaluate the effects of food on the pharmacokinetic
      profiles after single dose of IMMH-010 in patients with advanced solid tumors.
    

Trial Arms

NameTypeDescriptionInterventions
IMMH-010-60mgExperimentalPart A Dose escalation study: 60mg, QD, Cycle0Day1, Cycle1Day1-CycleN
  • IMMH-010
IMMH-010-120mgExperimentalPart A Dose escalation study:120mg, QD, Cycle0Day1, Cycle1Day1- CycleN
  • IMMH-010
IMMH-010-240mgExperimentalPart A Dose escalation study: 240mg, QD, Cycle0Day1, Cycle1Day1- CycleN
  • IMMH-010
IMMH-010-360mgExperimentalPart A Dose escalation study:360mg, QD, Cycle0Day1, Cycle1Day1- CycleN
  • IMMH-010

Eligibility Criteria

        Inclusion Criteria:

        Subjects are eligible only if they meet all the following criteria:

          1. Age ≥ 18 years when they sign the informed consent form;

          2. Subjects are eligible only if they meet the following criteria:

               1. Part A and B: patients with advanced or metastatic solid tumors that are
                  confirmed by cytological or histological examination, who did not respond to
                  standard treatment regimens, or did not tolerate these regimens, or had no
                  effective standard treatment regimens, or refused standard treatment regimens;

               2. Part C:Patients who have experienced disease progression after platinum-based
                  chemotherapy and one other systemic therapy and have cytologically or
                  histologically confirmed stage IV disease or have stage IIIB or IIIC (AJCC
                  Edition 8) non-small cell lung cancer (NSCLC) ineligible for local therapy, with
                  EGFR wild type and without ALK gene rearrangement. According to the expression of
                  PD-L1 in the tumor, the subjects are divided into the following 3 groups:

             Group C1: Subjects with disease progression after previous platinum-based chemotherapy
             and one other systemic therapy for NSCLC, with high PD-L1 expression (TPS ≥ 50%);
             Group C2: Subjects with disease progression after previous platinum-based chemotherapy
             and one other systemic therapy for NSCLC, with low PD-L1 expression (TPS: 1-49%,
             inclusive); Group C3: Subjects with disease progression after previous platinum-based
             chemotherapy and one other systemic therapy for NSCLC, with no PD-L1 expression (TPS <
             1%); Remarks: Subjects participating in the expansion study should provide archival
             tumor specimens (<6 months) or fresh biopsy specimens within 28 days prior to the
             initial dosing (excluding bone biopsy) to determine the expression level of PD-L1
             before entering the group. Subjects should provide fresh biopsy specimens before
             entering the group if they have received systemic treatment or local treatment (i.e.,
             radiotherapy [RT] or chemoradiotherapy [CRT]) after collection of archival biopsy
             specimens. The archival specimen is a formalin-fixed tumor tissue specimen from a
             tumor lesion that is biopsied at or after the diagnosis of metastatic disease, and
             from a site that has not been previously irradiated. It is not allowed to analyze the
             specimens biopsied prior to dosing in patients who have received any systemic therapy
             for the tumor (including neoadjuvant / adjuvant therapy).

          3. The ECOG score is 0 or 1 point (see the scoring criteria in Appendix 1);

          4. Based on RECIST 1.1 (see the scoring criteria in Appendix 4), subjects of Part C
             should have at least one measurable lesion, and those of Part A or B could have no
             measurable lesion;

             Definition of measurable lesion:

               1. Tumor lesion: The size must be accurately measurable on two mutually
                  perpendicular diameters, and both diameters must be ≥10 mm or ≥2 times of the
                  slice thickness

               2. Lymph node lesion: The size must be accurately measurable on two mutually
                  perpendicular diameters, and both diameters must be ≥15 mm or ≥2 times of the
                  slice thickness

          5. In subjects who had received other treatments, the toxic and side effects should
             return to grade ≤ 1 or to the baseline (NCI-CTCAE 5.0, excluding alopecia);

          6. The expected survival time should be at least 3 months;

          7. The subjects of Part A and B should give their consent to providing blood samples for
             the exploratory analysis and are free to provide tumor tissue specimens; while the
             subjects of Part C should provide sufficient archived sections of tumor tissues or
             fresh tumor tissues for PD-L1 detection;

          8. Subjects should have appropriate organ and bone marrow functions, and have laboratory
             test results within the following ranges before entering the group:

             Bone marrow reserve (within 14 days, no transfusion of blood or blood products, or no
             correction by G-CSF or other hematopoietic stimulate factors): absolute neutrophils
             count (ANC) ≥1.5×109/L; hemoglobin (HB) ≥90 g/L; and platelet (PLT) ≥75×109/L; Liver
             function: ALT≤2.5×ULN; AST≤2.5×ULN; ALP≤2.5×ULN; TBIL≤1.5×ULN (patients with known
             Gilbert's disease are eligible if their serum bilirubin level ≤3×ULN; and patients
             with metastases to liver are eligible if their ALT≤5×ULN, AST≤5×ULN, and ALP≤5×ULN);
             and albumin ≥3 g/dL; Kidney function: creatinine ≤1.5×ULN or creatinine clearance ≥45
             mL/min as calculated according to Cockcroft-Gault formula (refer to Appendix 2); Blood
             coagulation function: INR, PT, and APTT≤1.5×ULN (in patients not on anticoagulants;
             and it is decided by investigators whether patients on anticoagulants are eligible);
             Cardiac enzymes CK and CKMB measures are within the normal range; Thyroid function
             measures are within the normal range or mildly abnormal but requiring no treatment.

          9. Fertile eligible patients (males and females) must give their consent to taking
             reliable contraceptive measures (hormone, barrier, or sexual abstinence) throughout
             the trial and at least 4 months after the last dosing; reproductive-age females must
             have negative blood or urine pregnancy test within 7 days prior to enrollment;

         10. The subjects must give their informed consent for the study and signed ICF voluntarily
             before the trial;

         11. The subjects or the statutory agents should be able to communicate well and complete
             the study complying with the protocol.

        Exclusion Criteria:

        Subjects are excluded if they meet one of the following exclusion criteria.

          1. Subjects with a past history of pulmonary fibrosis or interstitial pneumonia,
             including pneumoconiosis or radiation fibrosis of lung beyond the exposure field,
             which is clinically significant as judged by the investigators;

          2. Subjects who have received systemic glucocorticoid or any immunosuppressive agents for
             some condition within 14 days prior to the initial dosing, excluding local
             glucocorticoid via nose spray, aspiration, or other route, or systemic glucocorticoid
             at a physiological dose (namely not exceeding 10 mg/d of prednisone or an equivalent
             dose of other glucocorticoids); corticosteroids are allowed in subjects for
             pretreatment for venous contrast agent allergic reaction (scanning-relevant) in the
             study period, but it should be recorded.

          3. Subjects who are expected to receive other systemic antineoplastic treatments in the
             study period;

          4. Subjects with risks of intestinal obstruction or intestinal perforation, such as a
             history of diverticulitis, intra-abdominal abscess, active ulcer, GI tract
             obstruction, or abdominal cancer;

          5. Subjects who are diagnosed with other malignant tumors within 5 years prior to the
             initial dosing, excluding eradicated basal cell carcinoma of skin, squamous cell
             carcinoma of skin, and / or radically resected in situ cancer;

          6. Subjects who ever received any organ transplants, including allogeneic stem cell
             transplantation, but excluding those requiring no immunosuppression (such as corneal
             transplant and hair transplant);

          7. Subjects with active metastasis to CNS and / or carcinomatous meningitis (including
             leptomeningeal carcinomatosis) with clinical symptoms or requiring intervention, which
             is unsuitable for the subjects to enter the group as judged by the investigators;

          8. Subjects with active autoimmune diseases in the past 1 year and consequently requiring
             systemic treatments (namely systemic steroids or immunosuppressive agents);

          9. Subjects with dysphagia;

         10. Subjects with refractory third lacunar effusion, such as massive pleural effusion and
             ascites;

         11. Subjects with gastrointestinal disorders that might affect drug absorption (such as
             Crohn's disease, ulcerative colitis, and subtotal gastrectomy);

         12. Subjects who received any immune checkpoint blockade therapy within 3 months prior to
             the initial dosing, or those who experienced grade ≥3 immune-related adverse events
             (ir AE) in the past immunotherapy period;

         13. Subjects who received major surgery within 4 weeks prior to the initial dosing or
             those whose wound did not completely heal yet; or subjects who received >30 Gy of
             chest radiotherapy within 6 months prior to the initial dosing;

         14. Subjects with a history of myocarditis, myocardial infarction, cerebrovascular
             accident, or NHYA≥2 congestive cardiac failure within 6 months prior to the initial
             dosing; or subjects with uncontrollable angina, unstable angina, or uncontrollable
             arrhythmia;

         15. Subjects who received other investigational drugs within 14 days or 5 half-lives (the
             longer duration shall prevail) prior to the initial dosing;

         16. Subjects who were vaccinated with live vaccines within 30 days prior to the initial
             dosing, and live-virus-free influenza vaccines are allowed;

         17. Subjects with active infections requiring systemic treatments (antibiotics); or
             subjects who meet any one of the following criteria:

               1. Subjects positive for human immunodeficiency virus (HIV) or with a known history
                  of acquired immune deficiency syndrome

               2. Subjects with infection of hepatitis B virus (HBV) or hepatitis C virus (HCV)
                  (definition: HBsAg-positive and HBV DNA copy number exceeding ULN, or
                  HCV-Ab-positive);

               3. Subjects with active tuberculosis (with an exposure history or positive
                  tuberculosis test, and with clinical and / or imaging manifestations).

               4. Subjects positive for treponema pallidum antibody.

         18. Subjects with a history of serious hypersensitivity reaction of drug;

         19. Pregnant or breast-feeding women;

         20. Subjects who were ineligible to participate in clinical trials as judged by the
             investigators.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity (DLT)
Time Frame:Part A Dose escalation study:At the end of Cycle 1 (Cycle0 is 7 days,Cycle1 is 21 days)
Safety Issue:
Description:To identify the dose-limiting toxicity (DLT) in dose escalation study.

Secondary Outcome Measures

Measure:Cmax
Time Frame:Part A Dose escalation study:At the end of Cycle1(Cycle0 is 7 days, Cycle1 is 21 days), Part B Food effect study: At the end of Cycle0(Cycle0 is 15 days), Part C Dose expansion study: At the end of Cycle1(Cycle1 is 21 days)
Safety Issue:
Description:Peak plasma concentration.
Measure:Tmax
Time Frame:Part A Dose escalation study:At the end of Cycle1(Cycle0 is 7 days, Cycle1 is 21 days), Part B Food effect study: At the end of Cycle0 (Cycle0 is 15 days), Part C Dose expansion study: At the end of Cycle1(Cycle1 is 21 days)
Safety Issue:
Description:Time to peak plasma concentration.
Measure:AUC
Time Frame:Part A Dose escalation study:At the end of Cycle1(Cycle0 is 7 days, Cycle1 is 21 days), Part B Food effect study: At the end of Cycle0 (Cycle0 is 15 days), Part C Dose expansion study: At the end of Cycle1(Cycle1 is 21 days)
Safety Issue:
Description:Area under the plasma concentration versus time curve.
Measure:Objective response rate (ORR)
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to approximately 2 years).
Safety Issue:
Description:ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1.
Measure:Duration of response (DOR)
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to approximately 2 years).
Safety Issue:
Description:DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1.
Measure:Disease control rate (DCR)
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to approximately 2 years).
Safety Issue:
Description:DCR is defined as the percentage of participants who have BOR of CR or PR or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1.
Measure:Progression-free survival (PFS)
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to approximately 2 years).
Safety Issue:
Description:PFS is defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Tianjin Chasesun Pharmaceutical Co., LTD

Last Updated

April 7, 2020