Clinical Trials /

IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma

NCT04109456

Description:

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.

Related Conditions:
  • Melanoma
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: IN10018-004-01
  • NCT ID: NCT04109456

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
IN10018BI 853520Part 1, Monotherapy Arm
CobimetinibCotellicPart 2, Combination Arm

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1, Monotherapy ArmExperimentalThe safety and tolerability of IN10018 monotherapy will be assessed. Other dose levels may be explored if necessary.
  • IN10018
Part 2, Combination ArmExperimentalThe 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.
  • IN10018
  • Cobimetinib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of IN10018 monotherapy
Time Frame:The first 21-day cycle
Safety Issue:
Description:Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Secondary Outcome Measures

Measure:Pharmacokinetics (PK) : Cmax
Time Frame:Cycle 1 and Cycle 3
Safety Issue:
Description:Peak Plasma Concentration (Cmax)
Measure:Pharmacokinetics (PK) : AUC
Time Frame:Cycle 1 and Cycle 3
Safety Issue:
Description:Area under the plasma concentration versus time curve (AUC)
Measure:Pharmacokinetics (PK) : tmax
Time Frame:Cycle 1 and Cycle 3
Safety Issue:
Description:Time to Cmax (tmax)
Measure:Pharmacokinetics (PK) : t1/2
Time Frame:Cycle 1 and Cycle 3
Safety Issue:
Description:Elimination half-life (t1/2)
Measure:Pharmacokinetics (PK) : CL/F
Time Frame:Cycle 1 and Cycle 3
Safety Issue:
Description:apparent clearance (CL/F)
Measure:Pharmacokinetics (PK) : Vd
Time Frame:Cycle 1 and Cycle 3
Safety Issue:
Description:Apparent volume of distribution(Vd)
Measure:Overall Response Rates using RECiST1.1 criteria
Time Frame:1 year
Safety Issue:
Description:Proportion of participants with (complete response, partial response, stable disease, progressive disease)
Measure:Disease Control Rate using RECiST1.1 criteria
Time Frame:1 year
Safety Issue:
Description:Proportion of subjects who have disease control (CR, PR or stable disease (SD))
Measure:duration of response (DOR)
Time Frame:1 year
Safety Issue:
Description: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.
Measure:progression free survival (PFS)
Time Frame:1 year
Safety Issue:
Description: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.
Measure:overall survival (OS)
Time Frame:1 year
Safety Issue:
Description:OS is defined as the time from the first day of study treatment to death due to any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:InxMed (Shanghai) Co., Ltd.

Trial Keywords

  • uveal
  • NRAS

Last Updated

March 16, 2020