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

Phase 2

Terminated

Conditions: Squamous Cell Carcinoma of Head and Neck

Interventions: Drug: CMP-001
Drug: Pembrolizumab

Registration Number: NCT04633278

Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary: 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: Former Sponsor Checkmate Pharmaceuticals

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

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:
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CMP-001 and Pembrolizumab	CMP-001	All subjects will receive CMP-001 IT and pembrolizumab IV according to the treatment schedule until a reason for treatment discontinuation is reached.
CMP-001 and Pembrolizumab	Pembrolizumab	All subjects will receive CMP-001 IT and pembrolizumab IV according to the treatment schedule until a reason for treatment discontinuation is reached.

Primary Outcome Measures

Name	Time	Method
Confirmed Objective Response Rate (ORR)	Up to approximately 109 weeks	Confirmed ORR is defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by Investigator assessment (IA).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any Serious TEAE, and Any TEAE Leading to Discontinuation or Death	Up to approximately 109 weeks	TEAE is defined as an AE that started or worsened in severity on or after the date that study drug was first administered (W1D1) until 30 days after the last dose of study treatment.
Severity of TEAEs as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0	Up to approximately 109 weeks	NI CTCAE Adverse Event Grades: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2 Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate instrumental activities of daily living Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limited self-care activities of daily living Grade 4 Life-threatening consequences: urgent intervention indicated Grade 5 Death related to adverse event
Duration of Response (DOR)	Up to approximately 28 months (120 weeks)	DOR, defined as the time from date of first documented response (CR or PR) to date of documented PD, based on RECIST v1.1 by Investigator assessment (IA).
Duration of Progression-free Survival (PFS)	Up to approximately 28 months (120 weeks)	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.
Duration of Overall Survival (OS)	From first dose up to approximately 28 months (120 weeks)	Overall survival (OS) is defined as the time from the first dose date of the study treatment to the date of death from any cause.
Immune Objective Response Rate (iORR)	Up to approximately 109 weeks	Immune objective response rate (iORR), defined as the percentage of participants who have an immune best overall response (iBOR) of immune complete response (iCR) or immune partial response (iPR) based on the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) as determined by Investigator.
Immune Progression-free Survival (iPFS)	Up to approximately 28 months (120 weeks)	iPFS, defined as the time from date of first dose of study drug to date of immune Confirmed Progressive Disease (iCPD) based on immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) by IA or death, whichever occurs first.
Confirmed ORR Based on Human Papillomavirus (HPV) Status	Up to approximately 109 weeks	Confirmed ORR is defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by Investigator assessment (IA) based on HPV status.
Confirmed ORR Based on Programmed Death-ligand 1 (PD-L1) Expressions	Up to approximately 109 weeks	Confirmed ORR is defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by Investigator assessment (IA) based on PD-L1 expressions (combined positive score \[CPS\] ≥ 1 and CPS ≥ 20)
Duration of PFS Based on HPV Status	Up to approximately 28 months (120 weeks)	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. PFS based on HPV status
Immune Duration of Response (iDOR)	Up to approximately 28 months (120 weeks)	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.
DOR Based on HPV Status	Up to approximately 28 months (120 weeks)	DOR, defined as the time from date of first documented response (CR or PR) to date of documented PD, based on RECIST v1.1 by Investigator assessment (IA). DOR based on HPV status.
DOR Based on PD-L1 Expressions	Up to approximately 28 months (120 weeks)	DOR, defined as the time from date of first documented response (CR or PR) to date of documented PD, based on RECIST v1.1 by Investigator assessment (IA). DOR based on PD-L1 expressions (combined positive score \[CPS\] 20).
PFS Based on PD-L1 Expressions	Up to approximately 28 months (120 weeks)	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. PFS based on PD-L1 expressions (combined positive score \[CPS\] 20).

Trial Locations

Locations (19): University of Chicago Medical Center
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Chicago, Illinois, United States
University of Southern California: Norris Oncology/Hematology - Newport Beach
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Newport Beach, California, United States
University of California - San Diego
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La Jolla, California, United States
Stephenson Cancer Center
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Oklahoma City, Oklahoma, United States
University of Arkansas for Medical Sciences
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Little Rock, Arkansas, United States
UCLA Hematology-Oncology
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Los Angeles, California, United States
University Cancer & Blood Center
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Athens, Georgia, United States
Barbara Ann Karmanos Cancer Institute
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Detroit, Michigan, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
UPMC - Hillman Cancer Center
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Pittsburgh, Pennsylvania, United States
Houston Methodist Hospital/Cancer Center
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Houston, Texas, United States
University of Southern California - Norris Comprehensive Cancer Center
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Los Angeles, California, United States
University of Iowa Hospitals & Clinics
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Iowa City, Iowa, United States
Vanderbilt University Medical Center
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Nashville, Tennessee, United States
University of Vermont Medical Center
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Burlington, Vermont, United States
Atlantic Health
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Morristown, New Jersey, United States
University of Tennessee
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Knoxville, Tennessee, United States
Nebraska Methodist Hospital
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Omaha, Nebraska, United States
Bon Secours St. Francis Cancer Center
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Greenville, South Carolina, United States