Clinical Trials /

CMP-001 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

NCT04633278

Description:

CMP-001-007 is a Phase 2 study of CMP-001 intratumoral (IT) and pembrolizumab intravenous (IV) administered to participants with head and neck squamous cell carcinoma (HNSCC) who have not been previously treated with a programmed cell death protein 1 (PD-1) blocking antibody. The primary objective of the study is to determine the Investigator-assessed confirmed objective response with CMP-001 in combination with pembrolizumab in subjects with head and neck squamous cell carcinoma (HNSCC) The secondary objectives are to: - To evaluate the safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with pembrolizumab in subjects with HNSCC - To evaluate the efficacy of CMP-001 in combination with pembrolizumab in subjects with HNSCC - To evaluate the effect of human papillomavirus (HPV) infection and programmed death-ligand 1 (PD-L1) expressions on the efficacy of CMP-001 in combination with pembrolizumab Participants will continue to receive treatment of CMP-001 and pembrolizumab according to the treatment schedule until a reason for treatment discontinuation is reached.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CMP-001 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
  • Official Title: A MULTICENTER, PHASE 2, OPEN-LABEL STUDY OF INTRATUMORAL CMP-001 IN COMBINATION WITH INTRAVENOUS PEMBROLIZUMAB IN SUBJECTS WITH RECURRENT OR METASTATIC HEAD AND NECK SQUAMOUS CELL CARCINOMA

Clinical Trial IDs

  • ORG STUDY ID: CMP-001-007
  • NCT ID: NCT04633278

Conditions

  • Carcinoma, Squamous Cell of Head and Neck

Interventions

DrugSynonymsArms
CMP-001CMP-001 and Pembrolizumab
PembrolizumabKeytrudaCMP-001 and Pembrolizumab

Purpose

CMP-001-007 is a Phase 2 study of CMP-001 intratumoral (IT) and pembrolizumab intravenous (IV) administered to participants with head and neck squamous cell carcinoma (HNSCC) who have not been previously treated with a programmed cell death protein 1 (PD-1) blocking antibody. The primary objective of the study is to determine the Investigator-assessed confirmed objective response with CMP-001 in combination with pembrolizumab in subjects with head and neck squamous cell carcinoma (HNSCC) The secondary objectives are to: - To evaluate the safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with pembrolizumab in subjects with HNSCC - To evaluate the efficacy of CMP-001 in combination with pembrolizumab in subjects with HNSCC - To evaluate the effect of human papillomavirus (HPV) infection and programmed death-ligand 1 (PD-L1) expressions on the efficacy of CMP-001 in combination with pembrolizumab Participants will continue to receive treatment of CMP-001 and pembrolizumab according to the treatment schedule until a reason for treatment discontinuation is reached.

Trial Arms

NameTypeDescriptionInterventions
CMP-001 and PembrolizumabExperimentalAll subjects will receive CMP-001 IT and pembrolizumab IV according to the treatment schedule until a reason for treatment discontinuation is reached.
  • CMP-001
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically- or cytologically-confirmed recurrent or metastatic HNSCC considered
             incurable by local therapies.

          -  No prior systemic therapy in the recurrent or metastatic setting. Systemic therapy as
             part of multi-modal treatment for locally advanced disease is allowed.

          -  Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx.
             Participants may not have a primary tumor site of nasopharynx (any histology).

          -  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.

          -  Combined Positive Score (CPS) ≥ 1 for PD-L1 on Immunohistochemistry (IHC) of tumor
             tissue.

          -  Have results of tumor HPV p16 by IHC for oropharyngeal cancer.

          -  Measurable disease as defined by RECIST v1.1, and both of the following:

               1. At least 1 lesion amenable to repeated Intratumoral (IT) injection.

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

          -  Adequate organ function based on most recent laboratory values within 3 weeks before
             the first dose of study drug on Week 1 Day 1 (W1D1) Eastern Cooperative Oncology Group
             (ECOG) Performance Status of 0 to 1 at Screening.

          -  Capable of understanding and complying with protocol requirements.

          -  Women of childbearing potential must have negative serum pregnancy test during
             Screening and be willing to use an adequate method of contraception from the time of
             consent until at least 120 days after the last dose of study drug.

          -  Male subjects must be surgically sterile or must agree to use adequate method of
             contraception from the time of consent until at least 120 days after the last dose of
             study drug.

          -  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:

          -  Disease suitable for local therapy administered with curative intent.

          -  Has PD within 3 months of completion of curatively intent systemic treatment for
             locoregionally advanced HNSCC.

          -  Radiation therapy (or other non-systemic therapy) within 2 weeks before the first dose
             of study drug on W1D1.

          -  Received prior therapy with PD-1 or PD-L1 blocking antibody therapy in the recurrent/
             metastatic setting. If PD-1 or PD-L1 blocking antibody therapy was given as part of
             curative intent therapy, it must be at least 1 year since receipt of PD-1 or PD-L1
             blocking antibody.

          -  Not fully recovered from adverse events (to Grade 1 or less [per CTCAE v5.0]), with
             the exception of persistent alopecia, neuropathy, ototoxicity, hypothyroidism, pain,
             or dysphagia, due to prior treatment.

          -  Requires systemic pharmacologic doses of corticosteroids greater than the equivalent
             of 10 mg/day prednisone within 30 days before the first dose of study drug 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.

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

          -  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, implanted or
             continuous use of a pacemaker or defibrillator.

          -  Known history of immunodeficiency.

          -  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 non-detectable prostate-specific antigen, in
             situ cervical cancer on biopsy or a squamous intraepithelial lesion on Papanicolaou
             smear, and thyroid cancer (except anaplastic).

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

          -  Untreated, symptomatic, or enlarging central nervous system (CNS) metastases or
             carcinomatous meningitis.

          -  Prior allogenic tissue/solid organ transplant.

          -  Active infection requiring systemic therapy.

          -  Known or suspected active infection with SARS-CoV-2 virus.

          -  Known or suspected infection with human immunodeficiency virus, hepatitis B virus or
             hepatitis C virus; testing is not required unless suspected.

          -  Received a live virus vaccination within 30 days before the start of study drug dosing
             on W1D1.

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

          -  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 trial.

          -  Participation in another clinical trial of an investigational anticancer therapy or
             device within 30 days before the first dose of study drug.

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

          -  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.

          -  Received previous CMP-001 treatment.

          -  Pregnant or breast-feeding or expecting to conceive or father children within the
             projected duration of the study, from the time of consent until at least 120 days
             after the last dose of study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The objective response (investigator-assessed) to CMP-001 in combination with pembrolizumab in subjects with head and neck squamous cell carcinoma (HNSCC).
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:Objective response is the proportion of subjects that experience confirmed complete or partial response based on RECIST v1.1.

Secondary Outcome Measures

Measure:Safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with pembrolizumab in subjects with HNSCC.
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:As determined by adverse events, serious adverse events, adverse events leading to discontinuation or death, and severity of adverse events (per NCI CTCAE v 5.0).
Measure:Efficacy [characterized by DOR, PFS, and OS, along with Immune Objective Response Rate (iORR), Immune Duration of Response (iDOR), and Immune Progression-free Survival (iPFS)] of CMP-001 in combination with pembrolizumab in subjects with HNSCC.
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:Duration of Response (DOR), defined as the time from date of first documented response (CR or PR) to date of documented progressive disease (PD), based on RECIST v1.1 by Investigator assessment (IA). Progression-free Survival (PFS), defined as the time from date of first dose of study drug to date of documented PD based on RECIST v1.1 by IA or death, whichever occurs first. Overall Survival (OS), defined as the time from the date of first dose of study drug to the date of death. iORR, defined as 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. iDOR, defined as the time from the date of the first immune response (iCR or iPR) to the date of immune confirmed progressive disease (iCPD) by IA. iPFS, defined as the time from date of first dose of study drug to date of iCPD by IA or death, whichever occurs first.
Measure:The effect of human papillomavirus (HPV) infection and programmed death ligand 1 (PD-L1) expressions on the efficacy of CMP-001 in combination with pembrolizumab.
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:Evaluated by examining ORR (see above), DOR (see above), and PFS (see above) based on HPV status and PD-L1 expressions (combined positive score [CPS] 20).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Checkmate Pharmaceuticals

Last Updated

November 18, 2020