IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma
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
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:
|
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:
Drug: Cobimetinib
60mg , orally once daily from day 1 to day 21 in a 28-day cycle
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- Pharmacokinetics (PK) : Cmax [Cycle 1 and Cycle 3]
Peak Plasma Concentration (Cmax)
- Pharmacokinetics (PK) : AUC [Cycle 1 and Cycle 3]
Area under the plasma concentration versus time curve (AUC)
- Pharmacokinetics (PK) : tmax [Cycle 1 and Cycle 3]
Time to Cmax (tmax)
- Pharmacokinetics (PK) : t1/2 [Cycle 1 and Cycle 3]
Elimination half-life (t1/2)
- Pharmacokinetics (PK) : CL/F [Cycle 1 and Cycle 3]
apparent clearance (CL/F)
- Pharmacokinetics (PK) : Vd [Cycle 1 and Cycle 3]
Apparent volume of distribution(Vd)
- Overall Response Rates using RECiST1.1 criteria [1 year]
Proportion of participants with (complete response, partial response, stable disease, progressive disease)
- Disease Control Rate using RECiST1.1 criteria [1 year]
Proportion of subjects who have disease control (CR, PR or stable disease (SD))
- 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.
- 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.
- 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
- To explore potential predictive biomarkers [through study completion, an average of 1 year]
the level of Phospho-FAK [Tyr 397]
Eligibility Criteria
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.
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.- IN10018-004-01