IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma

Sponsor
InxMed (Shanghai) Co., Ltd. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04109456
Collaborator
(none)
52
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2
39.5
10.4
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Study Details

Study Description

Brief Summary

This is a phase Ib, open label clinical study to evaluate the safety, tolerability, PK and antitumor activities of IN10018 as monotherapy and in combination with cobimetinib in subjects with metastatic uveal melanoma and NRAS-mutant metastatic melanoma.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Subjects with metastatic uveal melanoma (UM) or with NRAS-mutant metastatic melanoma will be enrolled.

IN10018 will be assessed firstly as monotherapy, and then in combination with cobimetinib.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
52 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
The safety and tolerability of IN10018 monotherapy will be assessed firstly. Other dose levels may be explored if necessary. And then the safety and tolerability of IN10018 in combination with Cobimetinib will be evaluated.The safety and tolerability of IN10018 monotherapy will be assessed firstly. Other dose levels may be explored if necessary. And then the safety and tolerability of IN10018 in combination with Cobimetinib will be evaluated.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib, Open-label Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of IN10018 as Monotherapy and Combination Therapy in Subjects With Metastatic Melanoma
Actual Study Start Date :
Mar 16, 2020
Anticipated Primary Completion Date :
Dec 30, 2022
Anticipated Study Completion Date :
Jun 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1, Monotherapy Arm

The safety and tolerability of IN10018 monotherapy will be assessed. Other dose levels may be explored if necessary.

Drug: IN10018
100 mg, orally once daily continuously
Other Names:
  • BI 853520
  • Experimental: Part 2, Combination Arm

    The safety and tolerability of IN10018 in combination with Cobimetinib will be assessed. Other dose levels may be explored if necessary. A modified 3+3 design will be used.

    Drug: IN10018
    100 mg, orally once daily continuously
    Other Names:
  • BI 853520
  • Drug: Cobimetinib
    60mg , orally once daily from day 1 to day 21 in a 28-day cycle
    Other Names:
  • Cotellic
  • Outcome Measures

    Primary Outcome Measures

    1. Safety and tolerability of IN10018 monotherapy [The first 21-day cycle]

      Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

    2. Safety and tolerability of IN10018 in combination with cobimetinib [The first 28-day cycle]

      Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

    Secondary Outcome Measures

    1. Pharmacokinetics (PK) : Cmax [Cycle 1 and Cycle 3]

      Peak Plasma Concentration (Cmax)

    2. Pharmacokinetics (PK) : AUC [Cycle 1 and Cycle 3]

      Area under the plasma concentration versus time curve (AUC)

    3. Pharmacokinetics (PK) : tmax [Cycle 1 and Cycle 3]

      Time to Cmax (tmax)

    4. Pharmacokinetics (PK) : t1/2 [Cycle 1 and Cycle 3]

      Elimination half-life (t1/2)

    5. Pharmacokinetics (PK) : CL/F [Cycle 1 and Cycle 3]

      apparent clearance (CL/F)

    6. Pharmacokinetics (PK) : Vd [Cycle 1 and Cycle 3]

      Apparent volume of distribution(Vd)

    7. Overall Response Rates using RECiST1.1 criteria [1 year]

      Proportion of participants with (complete response, partial response, stable disease, progressive disease)

    8. Disease Control Rate using RECiST1.1 criteria [1 year]

      Proportion of subjects who have disease control (CR, PR or stable disease (SD))

    9. duration of response (DOR) [1 year]

      For subjects who demonstrate CR or PR, DOR is defined as the time from first evidence of CR or PR until PD or death due to any cause, whichever occurs first.

    10. progression free survival (PFS) [1 year]

      PFS is defined as the time from the first day of study treatment to the first disease progression or death due to any cause, whichever occurs first.

    11. overall survival (OS) [1 year]

      OS is defined as the time from the first day of study treatment to death due to any cause.

    Other Outcome Measures

    1. To explore potential predictive biomarkers [through study completion, an average of 1 year]

      the level of Phospho-FAK [Tyr 397]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Written informed consent provided.

    • Histologically or cytologically confirmed metastatic uveal melanoma or Metastatic NRAS-mutant melanoma .

    • At least one measurable lesion can be accurately measured per RECIST 1.1 by investigator.

    • ECOG performance status of 0 or 1.

    • Adequate organ system functions as defined in the protocol

    • A male subject must agree to use contraception as detailed in protocol during the treatment period and through 30 days after the last dose of study treatment and must refrain from donating sperm during this period.

    • A female subject is eligible to participate if she is not pregnant, not breastfeeding.

    Key Exclusion Criteria:
    • Has had major surgery or significant traumatic injury within 28 days prior to first dose of study treatment, or anticipation of the need for major surgery during study treatment.

    • Has received prior systemic anticancer therapy including investigational agents, such as within 14 days or less than 5 half-lives (whichever is shorter) of chemotherapy or targeted therapy, or within 28 days of immunotherapy, prior to first dose of study treatment.

    • Has received prior radiotherapy within 14 days prior to first dose of study treatment.

    • Has received prior treatment of any FAK inhibitor (Part 1&2), or prior treatment of any MEK inhibitor (Part 2 only).

    • Has a known previous or concurrent cancer that is distinct in primary site or histology from current uveal melanoma within 3 years prior to first dose of study treatment, except for curatively treated cancers such as cervical carcinoma in situ).

    • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

    • Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases within 6 months before first dose of study treatment, or has any of the abnormality defined in protocol:

    • Part 2 only: Has history or current evidence of retinal pigmented epithelial detachment, central serous retinopathy, or retinal vein occlusion in the unaffected eye; or intraocular pressure > 21 mmHg or uncontrolled glaucoma (irrespective of intraocular pressure) in the unaffected eye.

    • Has known uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage prior to the first dose of study treatment.

    • Has malabsorption syndrome or inability to take oral drugs or Has clinically significant gastrointestinal abnormalities.

    • Known allergy or hypersensitivity to IN10018 and/or cobimetinib, or their ingredients.

    • Has an active infection requiring systemic therapy within 14 days prior to the first dose of study treatment.

    • Has known HIV/ active HBV/ active HCV infection.

    • subject is not suitable for participating this study based on the investigator's judgement.

    • has used Strong CYP3A inhibitors/inducers or P-gp inhibitors within 14 days prior to first dose of study treatment and during study treatment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Sylvester Comprehensive Cancer Center. Miami Florida United States 33136
    2 Massachusetts General Hospital Boston Massachusetts United States 02114
    3 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    4 Columbia University Medical Center New York New York United States 10032
    5 MD Anderson Houston Texas United States 77030

    Sponsors and Collaborators

    • InxMed (Shanghai) Co., Ltd.

    Investigators

    • Study Director: Eddie Xing, Dr., InxMed Shanghai

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    InxMed (Shanghai) Co., Ltd.
    ClinicalTrials.gov Identifier:
    NCT04109456
    Other Study ID Numbers:
    • IN10018-004-01
    First Posted:
    Sep 30, 2019
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by InxMed (Shanghai) Co., Ltd.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 31, 2022