Clinical Trials /

CMP-001 in Combination With Nivolumab in Subjects With Advanced Melanoma

NCT04698187

Description:

CMP-001-010 is a Phase 2 study of CMP-001 intratumoral (IT) and nivolumab intravenous (IV) administered to participants with refractory unresectable or metastatic melanoma. The primary objective of the study is to determine confirmed objective response with CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. The secondary objectives are to: - To evaluate the safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To evaluate the efficacy of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To assess the pharmacokinetic (PK) profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To assess and describe the immunogenicity of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CMP-001 in Combination With Nivolumab in Subjects With Advanced Melanoma
  • Official Title: A Multicenter, Open-label, Phase 2 Study of Intratumoral CMP-001 in Combination With Intravenous Nivolumab in Subjects With Refractory Unresectable or Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: CMP-001-010
  • NCT ID: NCT04698187

Conditions

  • Melanoma
  • Advanced Melanoma
  • Metastatic Melanoma
  • Unresectable Melanoma

Interventions

DrugSynonymsArms
CMP-001CMP-001 and Nivolumab
NivolumabOPDIVOCMP-001 and Nivolumab

Purpose

CMP-001-010 is a Phase 2 study of CMP-001 intratumoral (IT) and nivolumab intravenous (IV) administered to participants with refractory unresectable or metastatic melanoma. The primary objective of the study is to determine confirmed objective response with CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. The secondary objectives are to: - To evaluate the safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To evaluate the efficacy of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To assess the pharmacokinetic (PK) profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma. - To assess and describe the immunogenicity of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma.

Trial Arms

NameTypeDescriptionInterventions
CMP-001 and NivolumabExperimentalAll enrolled subjects will receive CMP-001 IT and nivolumab IV according to the treatment schedule until a reason for treatment discontinuation is reached.
  • CMP-001
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

        Subjects enrolled in the study must meet all of the following inclusion criteria to be
        eligible.

          1. Histopathologically-confirmed diagnosis of malignant melanoma that is metastatic or
             unresectable at Screening.

          2. Known BRAF mutation status; if BRAF V600 mutation positive, must have had prior
             treatment with a local Health Authority approved BRAF inhibitor, with or without
             mitogen-activated protein kinase inhibitor.

          3. Refractory to PD-1 blockade either as monotherapy or in combination with other
             therapies, as defined by the following criteria:

               1. Received treatment with a Food and Drug Administration approved PD-1 blocking
                  antibody for 12 weeks or longer.

               2. Have PD (according to RECIST v1.1) within 12 weeks of the last dose of a PD-1
                  blocking antibody, either as monotherapy or in combination with other agents.

             Evidence of confirmed PD must be established by BICR with an assessment at least 4
             weeks after the initial date of PD. The second assessment may serve as the Baseline
             for this study if completed within 30 days prior to the start of study treatment.

          4. Measurable disease, as defined by RECIST v1.1 and all of the following:

               1. At least 1 accessible lesion amenable to repeated IT injection.

               2. One or more measurable lesions at least 1 cm in diameter that are not intended
                  for CMP 001 injection and can be followed as target lesions per RECIST v1.1.

               3. Documented disease progression in any lesion that was previously radiated in
                  order to serve as a target lesion.

          5. Able to provide tissue from a core or excisional biopsy (fine needle aspirate is not
             sufficient). A newly obtained biopsy (within 90 days before the start of study
             treatment) is preferred but an archival sample is acceptable if no intervening therapy
             was received.

             Note: for tissue sampling details, please refer to the laboratory manual.

          6. Adequate organ function based on most recent laboratory values within 3 weeks before
             first dose of study treatment on Week 1 Day 1 (W1D1):

               1. Bone marrow function:

                    -  neutrophil count ≥ 1500/mm3

                    -  platelet count ≥ 100,000/mm3

                    -  hemoglobin concentration ≥ 9 g/dL

                    -  white blood cells ≥ 2000/mm3

               2. Liver function:

                    -  total bilirubin ≤ 1.5 times the upper limit of normal (ULN) with the
                       following exception: patients with Gilbert Disease total serum bilirubin ≤ 3
                       times ULN

                    -  aspartate aminotransferase and alanine aminotransferase ≤ 3 times the ULN

               3. Lactate dehydrogenase ≤ 2 times the ULN

               4. Renal function: estimated (Cockcroft-Gault) or measured creatinine clearance ≥ 30
                  mL/min.

               5. Coagulation:

                    -  International normalized ratio or prothrombin time (PT) ≤ 1.5 times ULN,
                       unless subject is receiving anticoagulant therapy, as long as PT or partial
                       thromboplastin time (PTT) is within therapeutic range of intended use of
                       anticoagulants

                    -  Activated partial thromboplastin time or PTT ≤ 1.5 times ULN, unless subject
                       is receiving anticoagulant therapy, as long as PT or PTT is within
                       therapeutic range of intended use of anticoagulants

          7. Age ≥ 18 years at time of consent.

          8. Eastern Cooperative Oncology Group Performance Status of 0 to 1 at Screening.

          9. Capable of understanding and complying with protocol requirements.

         10. Women of childbearing potential must have negative serum pregnancy test prior to
             dosing at W1D1 and be willing to use an adequate method of contraception from the time
             of consent until at least 150 days after last dose of study treatment.

         11. Able and willing to provide written informed consent and to follow study instructions.
             Subjects unable to provide written informed consent on their own behalf will not be
             eligible for the study.

        Exclusion Criteria:

        Subjects presenting with any of the following will not qualify for entry into the study:

          1. Uveal, acral, or mucosal melanoma.

          2. Received radiation therapy (or other nonsystemic therapy) within 2 weeks before first
             dose of study treatment on W1D1. Patients should have recovered (ie, Grade ≤1 or at
             baseline) from radiation-related toxicities.

          3. Treatment with complementary medications (eg, herbal supplements or traditional
             Chinese medicines) to treat the disease under study within 2 weeks prior to start of
             study treatment. Refer to Section 4.4. for prohibited therapies.

          4. Requires systemic pharmacologic doses of corticosteroids greater than the equivalent
             of 10 mg/day prednisone within 30 days before first dose of study treatment on W1D1.

               1. Subjects who are currently receiving steroids at a prednisone-equivalent dose of
                  ≤ 10 mg/day do not need to discontinue steroids prior to enrollment.

               2. Replacement doses, topical, ophthalmologic, and inhalational steroids are
                  permitted.

          5. History of CTCAE v5.0 Grade 4 immune-related AE due to prior PD-1 blocking antibody.

          6. Not fully recovered from AEs (to Grade 1 or less [per CTCAE v5.0], with the exception
             of persistent alopecia, hypothyroidism, and adrenal insufficiency) due to prior
             treatment.

          7. Active pneumonitis, history of noninfectious pneumonitis that required steroids, or
             history of interstitial lung disease.

          8. Severe uncontrolled cardiac disease within 6 months of Screening, including but not
             limited to poorly controlled hypertension, unstable angina, myocardial infarction,
             congestive heart failure (New York Heart Association Class II or greater),
             pericarditis within the previous 6 months, cerebrovascular accident, or implanted or
             continuous use of a pacemaker or defibrillator.

          9. Known history of immunodeficiency.

         10. Known additional malignancy that is progressing or required active treatment within
             the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell
             carcinoma of the skin that has undergone potentially curative therapy, curatively
             treated localized prostate cancer with prostate-specific antigen level below 4.0
             ng/mL, in situ cervical cancer on biopsy or a squamous intraepithelial lesion on
             Papanicolaou smear, and thyroid cancer (except anaplastic), and adjuvant hormonal
             therapy for breast cancer > 3 years from curative-intent surgical resection.

         11. Active autoimmune disease that has required systemic treatment in past 2 years;
             replacement therapy is not considered a form of systemic treatment.

         12. Untreated, symptomatic, or enlarging central nervous system metastases or
             carcinomatous meningitis (including leptomeningeal metastases from solid tumors).

         13. Prior allogenic tissue/solid organ transplant.

         14. Active infection requiring systemic therapy.

         15. Known or suspected active infection with severe acute respiratory syndrome coronavirus
             2 virus.

         16. Known or suspected infection with human immunodeficiency virus, hepatitis B virus, or
             hepatitis C virus (testing is not required unless suspected).

         17. Received a live virus/attenuated vaccination within 30 days before first dose of study
             treatment on W1D1.

         18. Received blood products (including platelets or red blood cells) or colony stimulating
             factors (including granulocyte colony stimulating factor, granulocyte/macrophage
             colony stimulating factor, or recombinant erythropoietin) within 30 days before the
             start of Screening.

         19. History of allergy or hypersensitivity to nivolumab and/or any of its excipients.

         20. Any concurrent uncontrolled illness, including mental illness or substance abuse,
             which in the opinion of the Investigator would make the subject unable to cooperate or
             participate in the study.

         21. Participation in another clinical study of an investigational anticancer therapy or
             device within 30 days before first dose of study treatment on W1D1. Note:
             Participation in the follow-up phase (receiving no study treatment) of a prior study
             is allowed.

         22. Requires prohibited treatment (ie, non-protocol specified anticancer pharmacotherapy,
             surgery, or radiotherapy) for treatment of malignant tumor.

         23. Has a life expectancy of less than 3 months and/or has rapidly progressing disease
             (eg, tumor bleeding, uncontrolled tumor pain) in the opinion of the treating
             Investigator.

         24. Received previous CMP-001 treatment.

         25. Pregnant or breastfeeding or expecting to conceive or donate eggs within the projected
             duration of the study, from the time of consent until at least 150 days after last
             dose of study treatment for women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine confirmed objective response (ORR) with CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Defined as proportion of subjects with confirmed complete or partial response based on RECIST v1.1, per blinded independent central review (BICR).

Secondary Outcome Measures

Measure:Evaluate the safety and tolerability of CMP-001 administered by IT injection in combination with nivolumab
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Based on adverse events, serious AEs, AEs leading to discontinuation or death, and severity of AEs per NCI CTCAE v5.0 in subjects with refractory unresectable or metastatic melanoma.
Measure:Duration of response (DOR)
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Time from the date of first documented response (CR or PR) to the date of documented progressive disease (PD), based on RECIST v1.1 by BICR.
Measure:Treatment response in non-injected target lesions
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Treatment response in non-injected target lesions based on RECIST v1.1 by BICR.
Measure:Progression-free survival (PFS)
Time Frame:From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:The time from date of first dose of study treatment to date of documented PD based on RECIST v1.1 by BICR or death, whichever occurs first.
Measure:Overall survival (OS)
Time Frame:From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:The time from date of first dose of study treatment to date of death.
Measure:Immune objective response rate (iORR)
Time Frame:From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:The proportion of subjects with a best overall response (BOR) of immune complete response (iCR) or immune partial response (iPR) based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IA.
Measure:Immune duration of response (iDOR)
Time Frame:From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:The time from the date of the first immune response (iCR or iPR) to the date of immune confirmed progressive disease (iCPD) by IA.
Measure:Immune progression-free survival (iPFS)
Time Frame:From first dose of CMP-001 (Week 1 Day 1) until 30 days after the last CMP-001 injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:The time from date of first dose of study drug to date of iCPD by IA or death, whichever occurs first.
Measure:Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for maximum observed serum concentration
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Assess the PK profile for maximum observed serum concentration.
Measure:Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for area under the serum concentration-time curve from time zero to the last quantifiable time point
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Assess the PK profile for area under the serum concentration-time curve from time zero to the last quantifiable time point.
Measure:Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for area under the serum concentration-time curve from time zero extrapolated to infinity
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Assess the PK profile for area under the serum concentration-time curve from time zero extrapolated to infinity.
Measure:Assess the PK profile of CMP-001 in combination with nivolumab in subjects with refractory unresectable or metastatic melanoma for a terminal elimination half-life
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Assess the PK profile for terminal elimination half-life.
Measure:Assess and describe the immunogenicity of CMP-001 in combination with nivolumab by detecting development of anti-Qbeta antibodies in subjects with refractory unresectable or metastatic melanoma
Time Frame:From first dose of drug (Week 1 Day 1) until 30 days after the last drug injection (until a reason for treatment discontinuation occurs)
Safety Issue:
Description:Detecting and describing development of anti-Qbeta antibodies in subjects with refractory unresectable or metastatic melanoma.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Checkmate Pharmaceuticals

Last Updated

April 21, 2021