A Phase 1/2 Trial of Pembrolizumab in Combination With Imatinib in Patients With Locally Advanced or Metastatic Melanoma With c-KIT Mutation or Amplification
Overview
- Phase
- Phase 1
- Intervention
- Imatinib Mesylate
- Conditions
- Stage IIIA Skin Melanoma
- Sponsor
- Joanne Jeter
- Primary Endpoint
- BORR
- Status
- Withdrawn
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase I/II trial studies the side effects and how well pembrolizumab and imatinib mesylate work in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and imatinib mesylate may work better in treating patients with melanoma with c-KIT mutation or amplification that has spread to nearby tissue or other places in the body.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the best overall response rate (BORR = complete response + partial response) of the combination of pembrolizumab and imatinib for treatment of melanomas harboring c-Kit mutation or amplification. II. To evaluate the safety and adverse effect profile of the combination of pembrolizumab and imatinib in patients with melanomas harboring c-KIT aberrations (mutations or amplifications). SECONDARY OBJECTIVES: I. To assess the median time to progression (TTP), progression free survival (PFS), and overall survival (OS). TERTIARY OBJECTIVES: I. Assessment of programmed cell death ligand (PD-L)1 expression in melanoma patients with c-KIT aberrations before and after combined therapy. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and imatinib mesylate orally (PO) once daily (QD) on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and every 9 weeks for 1 year, and then every 12 weeks thereafter.
Investigators
Joanne Jeter
Principal Investigator
Ohio State University Comprehensive Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Patient must have histologically or cytologically confirmed diagnosis of stage III melanoma inoperable/not amenable to local treatment or stage IV melanoma.
- •Patient must have either mutation or amplification of c-KIT gene tested by commercially available molecular or gene sequencing techniques
- •Be willing and able to provide written informed consent/assent for the trial
- •Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- •Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- •Absolute neutrophil count (ANC) \>= 1,500 /mcL
- •Platelets \>= 100,000 / mcL
- •Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
- •Serum creatinine =\< 1.5 X upper limit of normal (ULN) or measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- •Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days prior to the first dose of trial treatment; individuals who are receiving systemic steroid therapy at a stable dose less than or equal to 10mg of prednisone per day or its equivalent will be permitted to participate
- •Has a known history of active TB (bacillus tuberculosis)
- •Hypersensitivity to pembrolizumab, imatinib, or any of its excipients
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
- •Note: subjects with =\< grade 2 neuropathy and/or alopecia are an exception to this criterion and may qualify for the study
- •Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- •Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids at a dose exceeding 10mg of prednisone per day or its equivalent for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
Arms & Interventions
Treatment (pembrolizumab, imatinib)
Patients receive pembrolizumab IV over 30 minutes on day 1 and imatinib mesylate orally PO QD on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Imatinib Mesylate
Treatment (pembrolizumab, imatinib)
Patients receive pembrolizumab IV over 30 minutes on day 1 and imatinib mesylate orally PO QD on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Treatment (pembrolizumab, imatinib)
Patients receive pembrolizumab IV over 30 minutes on day 1 and imatinib mesylate orally PO QD on days 1-21. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
BORR
Time Frame: Up to 4 years
Will be estimated with a 95% exact confidence interval.
Secondary Outcomes
- Change in PD-1 and PDL-1 expression levels(Baseline to 4 years)
- Incidence of adverse events assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0(Up to 4 years)
- OS(From registration until death from any cause, assessed up to 4 years)
- PFS(From registration until disease progression or death, assessed up to 4 years)
- TTP(From registration until disease progression or death, assessed up to 4 years)