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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04109456




Registration number
NCT04109456
Ethics application status
Date submitted
26/09/2019
Date registered
30/09/2019

Titles & IDs
Public title
IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma
Scientific 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
Secondary ID [1] 0 0
IN10018-004-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IN10018
Treatment: Drugs - Cobimetinib
Treatment: Other - Atezolizumab

Experimental: Part 1, Monotherapy Arm - The safety and tolerability of IN10018 monotherapy will be assessed. Other dose levels may be explored if necessary.

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.

Experimental: Part 3, Combination Arm - The safety and tolerability of IN10018 in combination with Cobimetinib and Atezolizumab will be assessed.


Treatment: Drugs: IN10018
100 mg or 50mg, orally once daily continuously;

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

Treatment: Other: Atezolizumab
biweekly 840 mg dose will be used in this study starting from Cycle 2.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of IN10018 monotherapy
Timepoint [1] 0 0
The first 21-day cycle
Primary outcome [2] 0 0
Safety and tolerability of IN10018 in combination with cobimetinib
Timepoint [2] 0 0
The first 28-day cycle
Primary outcome [3] 0 0
Safety and tolerability of IN10018 in combination with cobimetinib and atezolizumab
Timepoint [3] 0 0
All treatment period
Secondary outcome [1] 0 0
Pharmacokinetics (PK) : Cmax
Timepoint [1] 0 0
Cycle 1 and Cycle 3
Secondary outcome [2] 0 0
Pharmacokinetics (PK) : AUC
Timepoint [2] 0 0
Cycle 1 and Cycle 3
Secondary outcome [3] 0 0
Pharmacokinetics (PK) : tmax
Timepoint [3] 0 0
Cycle 1 and Cycle 3
Secondary outcome [4] 0 0
Pharmacokinetics (PK) : t1/2
Timepoint [4] 0 0
Cycle 1 and Cycle 3
Secondary outcome [5] 0 0
Pharmacokinetics (PK) : CL/F
Timepoint [5] 0 0
Cycle 1 and Cycle 3
Secondary outcome [6] 0 0
Pharmacokinetics (PK) : Vd
Timepoint [6] 0 0
Cycle 1 and Cycle 3
Secondary outcome [7] 0 0
Overall Response Rates using RECiST1.1 criteria
Timepoint [7] 0 0
1 year
Secondary outcome [8] 0 0
Disease Control Rate using RECiST1.1 criteria
Timepoint [8] 0 0
1 year
Secondary outcome [9] 0 0
duration of response (DOR)
Timepoint [9] 0 0
1 year
Secondary outcome [10] 0 0
progression free survival (PFS)
Timepoint [10] 0 0
1 year
Secondary outcome [11] 0 0
overall survival (OS)
Timepoint [11] 0 0
1 year

Eligibility
Key inclusion criteria
Key

1. Ability to understand and willingness to sign informed consent(s).
2. Male or female subjects = 18 years at the time of signing informed consent.
3. Histologically or cytologically confirmed metastatic melanoma with subtypes limited to:

1. Metastatic uveal melanoma, or
2. Metastatic NRAS-mutant melanoma harboring an NRAS activating mutations of Q61, G12, or G13 mutation per local laboratory (including local reference laboratory) results.
4. Requirements for previous therapy:

1. Uveal melanoma: Either be treatment naïve or have failed the most recent therapy for metastatic disease, or
2. 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.
3. 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)
4. Received a minimum of two cycles of anti-PD-1/PD-L1 therapy. (Part 3)
5. Consent to undergo tumor biopsies of accessible lesions, before and during treatment and at radiographic progression, for biomarker analyses (site dependent).
6. At least one measurable lesion can be accurately measured per RECIST 1.1 by investigator.
7. ECOG performance status of 0 or 1.
8. Life expectancy of at least 3 months as assessed by investigator.
9. Availability of fresh tumor tissue and/or archival tumor tissue at Screening if agreed by subjects.
10. Must have recovered from all AEs due to previous therapies to = Grade 1 (CTCAE 5.0) or stable status as assessed by investigator.
11. Adequate bone marrow, liver, renal, and coagulation function within 5 days prior to first dose of study treatment.
12. A male subject must agree to use contraception as detailed in Appendix 4 of this 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.
13. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:

1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4. OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the treatment period and through 30 days after the last dose of study treatment.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.
2. 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.
3. Has received prior radiotherapy or radioactive chemotherapy within 14 days prior to first dose of study treatment.
4. 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).
5. 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.
6. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
7. 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.
8. Prior history of Alport syndrome.
9. 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.
10. Has contraindications to anti-PD-1 or anti-PD-L1 immunotherapy (Part 3).
11. 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).
12. Current treatment with anti-viral therapy for HBV (Part 3).
13. Prior allogeneic stem cell or solid organ transplantation.
14. Active tuberculosis
15. 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).
16. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. (Part 3).
17. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on previous chest computed tomography (CT) scan.
18. Has a history of major cardiovascular, cerebrovascular, or thromboembolic diseases (e.g., congestive heart failure, acute myocardial infarction, unstable angina, atrial fibrillation, ventricular tachyarrhythmia, uncontrolled hypertension, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism) within 6 months before first dose of study treatment, or has any of the following abnormality:

* QTc interval > 480 msec (Fridericia formula), (patients with right bundle branch block is not required to have QTc if the block is stable and assessed as not clinically significant by the PI),
* Left ventricular ejection fraction (LVEF) < 50%,
* Arrhythmia with clinical significance, or
* Other heart diseases with clinical significance.
19. History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/ central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), neovascular macular degeneration, or uncontrolled glaucoma with intra-ocular pressures >21 mmHg in the eye(s) unaffected by melanoma. (Parts 2 and 3)
20. Has known uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage prior to the first dose of study treatment.
21. Has malabsorption syndrome or inability to take oral drugs.
22. Has clinically significant gastrointestinal abnormalities including uncontrolled gastrointestinal inflammatory lesions (Crohn's disease, or ulcerative colitis in active or uncontrolled gastrointestinal bleeding).
23. Known allergy or hypersensitivity to IN10018 cobimetinib and/or atezolizumab, or their ingredients.
24. Has had an active infection requiring systemic therapy within 14 days prior to the first dose of study treatment.
25. Has known human immunodeficiency virus (HIV) infection.
26. Has known active Hepatitis B or Hepatitis C virus infection.
27. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
28. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
29. Has had used below CYP3A inhibitors/inducers and P-gp inhibitors within 14 days prior to first dose of study treatment, or anticipation of the need to use them during study treatment:

* Part 1: Strong CYP3A inhibitors/inducers and P-gp inhibitors are prohibited at least 14 days prior to initiation of and during study treatment.
* Parts 2 and 3: Moderate and Strong CYP3A inhibitors/inducers and P-gp inhibitors are prohibited at least 14 days prior to initiation of and during study treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
St Vincent Hospital Sydney - Sydney
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
InxMed (Shanghai) Co., Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eddie Xing, Dr.
Address 0 0
InxMed Shanghai
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Eddie Xing, Dr.
Address 0 0
Country 0 0
Phone 0 0
9495200786
Fax 0 0
Email 0 0
eddie.xing@inxmed.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04109456