Clinical Trials /

Imatinib Mesylate in Combination With Pembrolizumab in Patients With Melanoma

NCT04546074

Description:

This is an open-labelled single arm trial of pembrolizumab and imatinib mesylate in subjects with unresectable or metastatic KIT-mutant melanoma that are refractory to standard therapy. The phase Ib and II study will be conducted to evaluate the safety, tolerability and response rate data of this combination therapy. KIT-mutant tumors will be confirmed in previously biopsied tumors. This analysis will be done by next-generation sequencing.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Imatinib Mesylate in Combination With Pembrolizumab in Patients With Melanoma
  • Official Title: Imatinib Mesylate in Combination With Pembrolizumab in Patients With Advanced KIT-mutant Melanoma Following Progression on Standard Therapy: a Phase I/II Trial

Clinical Trial IDs

  • ORG STUDY ID: N20190002
  • NCT ID: NCT04546074

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
Pembrolizumab and Imatinib mesylateTreatment
Pembrolizumab and Imatinib mesylateTreatment

Purpose

This is an open-labelled single arm trial of pembrolizumab and imatinib mesylate in subjects with unresectable or metastatic KIT-mutant melanoma that are refractory to standard therapy. The phase Ib and II study will be conducted to evaluate the safety, tolerability and response rate data of this combination therapy. KIT-mutant tumors will be confirmed in previously biopsied tumors. This analysis will be done by next-generation sequencing.

Detailed Description

      This trial is conducted as "Advanced medicine" authorized by the Ministry of Health, Labor,
      and Welfare (MHLW) in Japan, and in in conformance with Clinical Trial Act.

      PIb study is a dose-escalation study comprising two dose levels of imatinib mesylate with
      fixed dose of pembrolizumab to evaluate safety and tolerability and identify maximum
      tolerated dose/administered, and determine recommended phase 2 dose (RP2D).

      In PII study, a Simon's minimax two-stage design is employed.The treatment period with the
      combination therapy of both studies will continue every 21 days for up to 33 cycles
      (approximately 2 years) as long as subjects are receiving benefit from treatment and have not
      had disease progression or met any criteria for study withdrawal.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimental
  • Pembrolizumab and Imatinib mesylate
  • Pembrolizumab and Imatinib mesylate

Eligibility Criteria

        Inclusion Criteria:

          -  1. Be male or female subjects, age 20 years or older on day of signing consent.

             2. Have histologically confirmed melanoma.

             3. Have unresectable or metastatic melanoma with KIT mutations detected by
             next-generation sequencing which was performed at clinical laboratories accredited by
             international standards such as CLIA and CAP certification.

             4. Have progressed on treatment with an anti-PD-1/L1 mAb administered either as
             monotherapy, or in combination with other checkpoint inhibitors or other therapies.
             PD-1 treatment progression is defined by meeting all of the following criteria:

               1. Received at least 2 doses of an approved anti-PD-1/L1 mAb.

               2. Has demonstrated disease progression after PD-1/L1 as defined by RECIST 1.1. The
                  initial evidence of disease progression is to be confirmed by second assessment
                  no less than 4 weeks from the date of the first documented progressive disease,
                  in the absence of rapid clinical progression. This determination is made by the
                  investigator. Once progressive disease is confirmed, the initial date of
                  progressive disease documentation will be considered the date of disease
                  progression.

               3. Progressive disease has been documented within 12 weeks from the last dose of
                  anti-PD-1/L1 mAb or during the treatment. In adjuvant therapy, progressive
                  disease has been documented within 6 months from the last dose of anti-PD-1/L1
                  mAb or during the treatment.

                  5. Have no prior treatment with KIT inhibitors.

                  6. Have completed previous therapies 21 days prior to enrollment on study.

                  7. Have the presence of at least one measurable lesion by CT or MRI per RECIST
                  1.1 criteria as determined by the local site investigator/radiology assessment
                  within 14-days prior to enrollment on study.

                  8. Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

                  9. Have life expectancy of greater than 90 days.

                  10. Have known no active central nervous system (CNS) metastases. Subjects with
                  previously treated brain metastases may participate provided they are stable
                  (without evidence of progression by imaging for at least 28 days before
                  enrollment on study and any neurologic symptoms).

                  11. If female of childbearing potential, must be willing to use an adequate
                  method of contraception and agree not to breastfeed for the course of the study
                  through 120 days after the last dose of study medication. If male of childbearing
                  potential, must agree to use an adequate method of contraception for the course
                  of the study through 120 days after the last dose of study medication.

                  12. Have laboratory parameters within Protocol-defined range. The screening
                  laboratory tests below must be ≤14 days before enrollment on study.

               1. White blood cell count ≥ 2,000/mm^3 and absolute neutrophil count ≥1,500/mm^3.

               2. Platelets ≥ 100,000/mm^3.

               3. Hemoglobin ≥ 9 g/dL.

               4. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 150 IU/L.

               5. Bilirubin ≤ 2.0 mg/dl.

               6. Serum creatinine ≤ 1.5 mg/dl. 13. Be willing and able to review, understand and
                  provide written consent before starting therapy.

                  Exclusion Criteria:

          -  1. Be seropositive for hepatitis B antigen, or hepatitis C antibody. Even if negative
             for HBs antigen, subjects who are positive for HBs antibody or HBc antibody and amount
             of HBV-DNA exceed detection sensitivity are excluded from the study.

             2. Has known history of human immunodeficiency virus(HIV) (HIV 1/2 antibodies).

             3. Has a history of (no-infectious) pneumonitis that required steroids.

             4. Has ongoing or active infections, symptomatic heart failure, unstable angina
             pectoris, cardiac arrhythmias, interstitial pneumonia, pneumonitis, or psychiatric
             disorders that would interfere with cooperation with the requirements of the study.

             5. Has known superior vena cava syndrome, pericardial effusion, pleural effusion, or
             ascites of grade 3 or higher.

             6. Has presence of a gastrointestinal condition that may affect drug absorption.

             7. Receiving or necessary to continue administering CYP3A4 inhibitors or drugs
             metabolized by CYP3A4.

             8. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include cancers that have not recurred for at least 3 years before
             enrollment on study and early stage cancers (carcinoma in situ or stage 1) treated
             with curative intent, basal cell carcinoma of the skin, or superficial bladder cancer
             that has undergone potentially curative therapy.

             9. Has an active autoimmune disease that has required systemic treatment in past 2
             years.

             10. Has history of organ transplantation including hematopoietic stem cell
             transplantation.

             11. Receiving chronic systemic steroid therapy. Replacement therapy (e.g., thyroxine,
             insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
             insufficiency, etc.) is not considered a form of systemic treatment.

             12. Pregnant women and breastfeeding woman.

             13. Has received live vaccine within 30 days before the first dose of study treatment.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and
             typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus
             vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are
             live attenuated vaccines and are not allowed.

             14. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective in phase Ib study
Time Frame:at 6 weeks
Safety Issue:
Description:Dose Limiting Toxicities (DLT) rates of pembrolizumab and imatinib mesylate combination therapy

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From date of registration until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months.
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From date of registration until the date of to death from any cause, assessed up to 60 months.
Safety Issue:
Description:
Measure:Best overall response (BOR)
Time Frame:From date of initiation of treatment until the date of the end of treatment. The maximum period for treatment is 2 years.
Safety Issue:
Description:BOR is defined from the overall efficacy determined by the end of this trial according to RECIST 1.1
Measure:Incidence of adverse events (AEs) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame:Be followed up to 30 days after the cessation of treatment
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Keio University

Trial Keywords

  • KIT

Last Updated

September 4, 2020