Business Decision

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.

Former Sponsor Checkmate Pharmaceuticals

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.

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the Sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.