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.
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
Interventions
Drug | Synonyms | Arms |
---|
IN10018 | BI 853520 | Part 1, Monotherapy Arm |
Cobimetinib | Cotellic | Part 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
Name | Type | Description | Interventions |
---|
Part 1, Monotherapy Arm | Experimental | The safety and tolerability of IN10018 monotherapy will be assessed. Other dose levels may be explored if necessary. | |
Part 2, Combination Arm | Experimental | 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. | |
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
Last Updated
August 17, 2021