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

InxMed (Shanghai) Co., Ltd.8 sites in 2 countries51 target enrollmentMarch 16, 2020

ConditionsMetastatic Melanoma

InterventionsIN10018 Cobimetinib Atezolizumab

DrugsIN10018 Cobimetinib

Overview

Phase: Phase 1
Intervention: IN10018
Conditions: Metastatic Melanoma
Sponsor: InxMed (Shanghai) Co., Ltd.
Enrollment: 51
Locations: 8
Primary Endpoint: Safety and tolerability of IN10018 monotherapy
Status: Completed
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

Subjects with metastatic uveal melanoma (UM) or with NRAS-mutant metastatic melanoma will be enrolled. IN10018 will be assessed firstly as monotherapy（Part 1）, then in combination with cobimetinib (Part 2) and in combination with cobimetinib and Atezolizumab (Part 3).

Registry

clinicaltrials.gov

Start Date

March 16, 2020

End Date

December 20, 2024

Last Updated

3 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

InxMed (Shanghai) Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Ability to understand and willingness to sign informed consent(s).
•Male or female subjects ≥ 18 years at the time of signing informed consent.
•Histologically or cytologically confirmed metastatic melanoma with subtypes limited to:
•Metastatic uveal melanoma, or
•Metastatic NRAS-mutant melanoma harboring an NRAS activating mutations of Q61, G12, or G13 mutation per local laboratory (including local reference laboratory) results.
•Requirements for previous therapy:
•Uveal melanoma: Either be treatment naïve or have failed the most recent therapy for metastatic disease, or
•NRAS-mutant melanoma: Either be ineligible for standard of care due to the presence of various comorbidities or have failed the most recent therapy such as immunotherapy for metastatic disease.
•Have failed immunotherapy therapy (anti-PD-1 or anti-PD-L1) alone or in combination with other agents for metastatic disease either with no initial response or disease progression after an initial response. (Part 3)
•Received a minimum of two cycles of anti-PD-1/PD-L1 therapy. (Part 3)

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, intrahepatic, or sphere anticancer therapy including investigational agents 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 or radioactive chemotherapy within 14 days prior to first dose of study treatment.
•Has received prior treatment of any FAK inhibitor (Parts 1, 2 and 3), or prior treatment of any MEK inhibitor (Parts 2 and 3 only).
•Has a known previous or concurrent cancer that is distinct in primary site or histology from current melanoma within 3 years prior to first dose of study treatment, except for curatively treated cancers such as cervical carcinoma in situ and indolent cancers with very low likelihood of relapse or progress per investigator judgement.
•Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
•Diabetes mellitus, insulin dependent and non-insulin dependent with HBA1C \> 6.5%, microalbuminuria \> 150 mg (24-h collection), and CrCL of \< 45ml/min with an adequate 24-hour urine collection.
•Prior history of Alport syndrome.
•Recent medical history (with the last 1-year) of acute renal injury, Goodpasture's Syndrome, IgA nephropathy, focal segmental glomerulosclerosis, nephrotic syndrome, parenteral drug abuse, recurrent pyelonephritis, systemic lupus erythematosus, uncontrolled hypertension, vasculitis, and chronic illnesses with potential underlying glomerular renal disease.
•Has contraindications to anti-PD-1 or anti-PD-L1 immunotherapy (Part 3).

Arms & Interventions

Part 1, Monotherapy Arm

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

Intervention: IN10018

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.

Intervention: IN10018

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.

Intervention: Cobimetinib