IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma
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| ClinicalTrials.gov Identifier: NCT04109456 |
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Recruitment Status :
Not yet recruiting
First Posted : September 30, 2019
Last Update Posted : October 1, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Melanoma | Drug: IN10018 Drug: Binimetinib | Phase 1 |
Initially only subjects with metastatic uveal melanoma (UM) will be enrolled. Additional tumor types and cohorts such as mucosal melanoma with GNAQ/GNA11 mutations and melanoma with NRAS mutations may be added to explore further anti-tumor activities based on emerging data.
This study has 2 parts to enroll up to approximately 52 subjects. IN10018 will be assessed firstly as monotherapy in Part 1, and then in combination with binimetinib in Part 2. The recommended phase II dose (RP2D) of monotherapy or combination therapy will be determined during first component of Part 1 (Stage A) and Part 2 (Stage C), and then to be extended to further evaluate the antitumor activities of IN10018 monotherapy or combination therapy during second component of Part 1 (Stage B) and Part 2 (Stage D).
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 52 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | The safety and tolerability of IN10018 100 mg monotherapy will be assessed first in Part 1. Safety Monitoring Committee (SMC) will determine whether 100 mg can be used as the RP2D of monotherapy for further development. Other dose levels may be explored if necessary. Another approximately 10 subjects will be enrolled in Part 1 to further evaluate the antitumor activities if SMC thought that there is sufficient efficacy signal observed. Part 2 will be initiated once the RP2D of IN10018 monotherapy is determined in Part 1. Approximately 20 to 32 subjects will be enrolled to receive combination therapy of IN10018 and binimetinib in Part 2. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Estimated Study Start Date : | November 30, 2019 |
| Estimated Primary Completion Date : | March 20, 2021 |
| Estimated Study Completion Date : | March 20, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 1, Monotherapy Arm
The safety and tolerability of IN10018 100 mg monotherapy will be assessed first in Part 1. Safety Monitoring Committee will determine whether 100 mg can be used as the RP2D of monotherapy for further development. Other dose levels may be explored if necessary. |
Drug: IN10018
100 mg or 75 mg, orally once daily continuously in 21-day cycles.
Other Name: BI 853520 |
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Experimental: Part 2, Combination Arm
Part 2 will be initiated once the RP2D of IN10018 monotherapy is determined in Part 1. A modified 3+3 design is used for Part 2 to determine the PR2D of IN10018 and binimetinib for combination.
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Drug: IN10018
100 mg or 75 mg, orally once daily continuously in 21-day cycles.
Other Name: BI 853520 Drug: Binimetinib 45 mg or 30 mg, orally twice daily (approximately 12 hours apart) continuously in 21-day cycles.
Other Name: MEKTOVI |
- Safety and tolerability of IN10018 monotherapy in subjects with metastatic uveal melanoma [ Time Frame: 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 binimetinib in subjects with metastatic uveal melanoma in Part 2. [ Time Frame: The first 21-day cycle ]Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
- Pharmacokinetics (PK) of IN10018 and binimetinib: Cmax [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1(each cycle is 21 days). ]Peak Plasma Concentration (Cmax)
- Pharmacokinetics (PK) of IN10018 and binimetinib: AUC [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1(each cycle is 21 days). ]Area under the plasma concentration versus time curve (AUC)
- Pharmacokinetics (PK) of IN10018 and binimetinib: tmax [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1(each cycle is 21 days). ]Time to Cmax (tmax)
- Pharmacokinetics (PK) of IN10018 and binimetinib: t1/2 [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1(each cycle is 21 days). ]Elimination half-life (t1/2)
- Pharmacokinetics (PK) of IN10018 and binimetinib: CL/F [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1(each cycle is 21 days). ]apparent clearance (CL/F)
- Pharmacokinetics (PK) of IN10018 and binimetinib: Vd [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 3 Day 1(each cycle is 21 days). ]Apparent volume of distribution(Vd)
- Overall Response Rates using RECiST1.1 criteria [ Time Frame: 1 year ]Proportion of participants with (complete response, partial response, stable disease, progressive disease)
- Disease Control Rate using RECiST1.1 criteria [ Time Frame: 1 year ]Proportion of subjects who have disease control (CR, PR or stable disease (SD))
- duration of response (DOR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 1 year ]OS is defined as the time from the first day of study treatment to death due to any cause.
- To explore potential predictive biomarkers [ Time Frame: through study completion, an average of 1 year ]Test the level of Phospho-FAK [Tyr 397] from the baseline to explore the potential predictive biomarker.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key Inclusion Criteria:
- Written informed consent provided.
- Male or female subjects ≥ 18 years.
- Histologically or cytologically confirmed metastatic uveal 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 following abnormality:
QTc interval > 480 msec (Fridericia formula); OR Left ventricular ejection fraction (LVEF) < 50%; OR Arrhythmia with clinical significance; OR Other heart diseases with clinical significance.
- 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.
- Has clinically significant gastrointestinal abnormalities including uncontrolled gastrointestinal inflammatory lesions (Crohn's disease, or ulcerative colitis in active or uncontrolled gastrointestinal bleeding).
- Known allergy or hypersensitivity to IN10018 and/or binimetinib, or their ingredients.
- Has an active infection requiring systemic therapy within 14 days prior to the first dose of study treatment.
- Has known human immunodeficiency virus (HIV) infection.
- Has known active Hepatitis B or Hepatitis C virus infection.
- 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.
- Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
- Strong CYP3A inhibitors/inducers and P-gp inhibitors are prohibited at least 14 days prior to initiation of and during study treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04109456
| Contact: Richard Carvajal | 6463176330 | carvajalr@columbia.edu |
| Responsible Party: | InxMed (Shanghai) Co., Ltd. |
| ClinicalTrials.gov Identifier: | NCT04109456 History of Changes |
| Other Study ID Numbers: |
IN10018-004-01 |
| First Posted: | September 30, 2019 Key Record Dates |
| Last Update Posted: | October 1, 2019 |
| Last Verified: | September 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas |