IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma

NCT04109456 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IN10018-004-01
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 8

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.

Conditions

Metastatic Melanoma

Keywords

uveal; NRAS

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability of IN10018 monotherapy

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

  The first 21-day cycle

• Safety and tolerability of IN10018 in combination with cobimetinib

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

  The first 28-day cycle

• Safety and tolerability of IN10018 in combination with cobimetinib and atezolizumab

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

  All treatment period

Secondary Outcomes (11)

• Pharmacokinetics (PK) : Cmax

  Cycle 1 and Cycle 3

• Pharmacokinetics (PK) : AUC

  Cycle 1 and Cycle 3

• Pharmacokinetics (PK) : tmax

  Cycle 1 and Cycle 3

• Pharmacokinetics (PK) : t1/2

  Cycle 1 and Cycle 3

• Pharmacokinetics (PK) : CL/F

  Cycle 1 and Cycle 3

Other Outcomes (1)

• To explore potential predictive biomarkers

  through study completion, an average of 5 year

Study Arms (3)

Part 1, Monotherapy Arm

EXPERIMENTAL

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

Drug: IN10018

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.

Drug: IN10018; Drug: Cobimetinib

Part 3, Combination Arm

EXPERIMENTAL

The safety and tolerability of IN10018 in combination with Cobimetinib and Atezolizumab will be assessed.

Drug: IN10018; Drug: Cobimetinib; Biological: Atezolizumab

Interventions

IN10018 DRUG

100 mg or 50mg, orally once daily continuously;

Also known as: BI 853520

Part 1, Monotherapy Arm; Part 2, Combination Arm; Part 3, Combination Arm

Cobimetinib DRUG

60mg , orally once daily from day 1 to day 21 in a 28-day cycle

Also known as: Cotellic

Part 2, Combination Arm; Part 3, Combination Arm

Atezolizumab BIOLOGICAL

biweekly 840 mg dose will be used in this study starting from Cycle 2.

Part 3, Combination Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Consent to undergo tumor biopsies of accessible lesions, before and during treatment and at radiographic progression, for biomarker analyses (site dependent).
• At least one measurable lesion can be accurately measured per RECIST 1.1 by investigator.
• ECOG performance status of 0 or 1.
• Life expectancy of at least 3 months as assessed by investigator.
• Availability of fresh tumor tissue and/or archival tumor tissue at Screening if agreed by subjects.

You may not qualify if:

• 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).
• Has received prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA4 immunotherapy and was discontinued for significant immunotherapy-related adverse events (Part 3).
• Current treatment with anti-viral therapy for HBV (Part 3).
• Prior allogeneic stem cell or solid organ transplantation.
• Active tuberculosis
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina (Part 3).

Sponsors & Collaborators

• InxMed (Shanghai) Co., Ltd.: lead

Study Sites (8)

Sylvester Comprehensive Cancer Center.

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

St Vincent Hospital Sydney

Sydney, New South Wales, Australia

Location

The Alfred Hospital

Melbourne, Victoria, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, Australia

Location

MeSH Terms

Conditions

Melanoma

Interventions

cobimetinib; atezolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Eddie Xing, Dr.

  InxMed Shanghai

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The safety and tolerability of IN10018 monotherapy (Part 1) will be assessed firstly. Other dose levels may be explored if necessary. and then the safety and tolerability of IN10018 in combination with Cobimetinib (Part 2) will be evaluated. the safety and tolerability of IN10018 in combination with Cobimetinib and Atezolizumab (Part 3) will be evaluated .

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: September 30, 2019
• Study Start: March 16, 2020
• Primary Completion: December 20, 2024
• Study Completion: December 20, 2024
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); AU (3)