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

Study Overview
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Brief Summary
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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.

Detailed Description
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Former Sponsor Checkmate Pharmaceuticals

Official Title
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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

Conditions
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Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Drug: CMP-001
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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, larynx or paranasal sinus. 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: At least 1 lesion amenable to repeated Intratumoral (IT) injection. 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. Subjects who are currently receiving steroids at a prednisone-equivalent dose of ≤ 10 mg/day do not need to discontinue steroids prior to enrollment. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CMP-001 and Pembrolizumab<br>All subjects will receive CMP-001 IT and pembrolizumab IV according to the treatment schedule until a reason for treatment discontinuation is reached. | Drug: CMP-001<br>* Subjects will receive CMP-001 10mg weekly for 2 doses after which CMP-001 will be administered every 3 weeks. The first dose of CMP-001 may be administered subcutaneously (SC) or Intratumorally (IT) at the discretion of Investigator. All subsequent doses will be injected intratumorally every 3 weeks (Q3W).<br>* Other names: vidutolimod;Drug: Pembrolizumab<br>* Pembrolizumab 200 mg IV is administered Q3W.<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of CMP-001 administered by intratumoral (IT) injection in combination with pembrolizumab in subjects with HNSCC. | 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). | 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) | 
| 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. | 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. | 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) | 
| 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. | 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). | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Pembrolizumab, Carcinoma, HNSCC