Clinical Trial 22485

• Overview

  Study Title:

  A Phase II Study of ACR-368 and Low Dose Gemcitabine Combination Therapy in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

  Objective:

  Primary Objectives: * To determine overall response rate (ORR) by investigator review (IR) and blinded independent central review (BICR) in Cohort A (p16/HPV-negative) and Cohort B (p16/HPV-positive) R/M HNSCC given the ACR-368 and LDG combination therapy. Secondary Objectives: * To determine safety and tolerability. * To determine duration of response (DOR) by IR and BICR. * To estimate progression-free survival (PFS) by IR and BICR. * To estimate overall survival (OS)

• Treatments

  Therapies:

  Chemotherapy (NOS)

  Medications:

  ACR-368 (); Gemzar (gemcitabine); gemcitabine ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Must be at least 18 years of age at the time of consent.
  • Patient (or a legally authorized representative) must understand and voluntarily sign informed consent prior to any study-related assessments/procedures being conducted.
  • Must be able and willing to comply with the study visit schedule and protocol requirements.
  • Must have sufficient archived tumor tissue available for p16 immunohistochemistry (IHC) staining if the status is unknown. HPV status determined by HPV DNA sequencing, HPV DNA/RNA in situ hybridization, or equivalent assays using tumor tissue or cell free HPV DNA testing or equivalent using blood-based assays are also acceptable. If there is a discrepancy between p16 IHC and HPV detection assay results, HPV detection assay result will be used.
  • Must have sufficient archived tumor tissue available for OncoSignature determination. The tumor tissue must be less than 3 months old from the enrollment date. There should not be any intervening systemic therapy from the date of tumor tissue collection. If not, patient must agree to a fresh tumor biopsy before starting the treatments.
  • Must agree to a biopsy after the lead-in LDG infusion and at the time of disease progression (or end of treatment if applicable).
  • Must have R/M HNSCC including oral cavity, oropharynx, larynx, and hypopharynx. Patients with p16-positive or HPV-positive unknown primary of head and neck are eligible.
  • Must have been treated with one prior line of PD-1/PD-L1 inhibitor with/without chemotherapy. Patients who are immunotherapy ineligible due to history of autoimmune disease or steroid requirement (prednisone >10mg per day or equivalent) are allowed to enroll without the one prior line of PD-1/PD-L1 inhibitor with/without chemotherapy. There is no limitation on the number of prior therapies received in the R/M setting.
  • Must have at least one measurable lesion as defined by RECIST v1.1.
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Must meet the laboratory criteria defined in the protocol. Blood transfusion and/or blood product support are allowed.
  • Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective birth control with their partners starting at the time of informed consent and for 1 year after the completion of the study treatment regimen.
  • Other inclusion criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Patients should not have any prior systemic therapy for 4 weeks from the time of the study treatment.
  • Patients should not have any palliative radiation therapy for 2 weeks from the time of the study treatment. Palliative radiation therapy is permitted during the study treatment if it does not involve target lesions.
  • Patients with prior therapy-related toxicities Grade >1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0; except for dysphagia, alopecia, or vitiligo. Immunotherapy-related endocrinopathies stable for at least 1 month, and controlled with hormonal replacement, are not excluded. Grade 2 neuropathy stable for at least 2 weeks and controlled with supportive care medications are not excluded.
  • Patients with symptomatic and/or untreated brain metastases (of any size and any number). Patients with definitively treated brain metastases may be eligible, must be stable for at least 2 weeks and must be asymptomatic with or without prednisone > Patients who have a left ventricular ejection fraction (LVEF) > Patients with cardiovascular disease defined in the protocol.
  • Patients who have had another primary malignancy within the previous 3 years (except for those who do not require treatment or have been curatively treated >1 year ago, and in the judgment of the Investigator, do not pose a significant risk of recurrence; including, but not limited to, non-melanoma skin cancer, ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS], or prostate cancer Gleason score ≤6.).
  • Other exclusion criteria may apply.

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