PBI-MST-01(NCT04541108) Substudy TAK-02: Intratumoral Microdosing of TAK-676 in HNSCC

Inclusion Criteria:

1. Ability and willingness to comply with the study's visit and assessment schedule.
2. Male or female ≥ 18 years of age at Visit 1 (Screening).
3. Pathologic diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC).
4. Ability and willingness to provide written informed consent. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
5. At least one lesion (primary tumor, recurrent tumor, or effaced metastatic lymph node) ≥ 2 cm in the shortest diameter that is surface accessible for CIVO injection that may be guided by ultrasound if appropriate and for which there is a planned surgical intervention. Treatment plan may include adjuvant radiation or chemotherapy, and patients should have no medical contraindication to surgery.
6. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
7. Female patients who:

   * Are postmenopausal for at least one year before the screening visit, OR
   * Are surgically sterile, OR
   * Are of childbearing potential who agree to practice a highly effective method of contraception and one additional effective (barrier) method at the same time (see examples below) from the time of signing the informed consent form (ICF) through four months after the tumor injection procedure OR agree to completely abstain from heterosexual intercourse.

Highly effective methods:

* Intrauterine device (IUD)
* Hormonal (birth control pills/oral contraceptives, injectable contraceptives, contraceptive patches, or contraceptive implants

Other effective methods (barrier methods):

* Latex condom
* Diaphragm with spermicide; Cervical cap; Sponge
* Agree to refrain from donating ova during study participation and up to four months after the tumor injection procedure.

Male patients, even if surgically sterile (i.e., status post-vasectomy), who:

* Agree to practice effective barrier contraception from the time of signing the ICF through four months after the tumor injection procedure OR agree to completely abstain from heterosexual intercourse.
* Agree to refrain from donating sperm during study participation and up to four months after the tumor injection procedure.

Exclusion Criteria:

1. Tumors or effaced nodes that are anticipated by the Investigator to lack a sufficient volume of viable tumor tissue (based on available pre-operative imaging, pre-injection ultrasound imaging, or pathology reports) for CIVO injection due to size, location, necrosis, cysts, excessive stroma, or fibrosis.
2. Patients who have received neoadjuvant therapy associated with the surgical intervention described in Inclusion Criterion #5.
3. Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
4. Female patients who are:

   * Both lactating and breastfeeding, OR
   * Have a positive β-human chorionic gonadotropin (hCG) pregnancy test at screening verified by the Investigator.
5. Any uncontrolled intercurrent illness, condition, serious medical or psychiatric illness, or circumstance that, in the opinion of the Investigator, could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives.
6. Patients with a history of concurrent second cancers requiring active, ongoing systemic treatment.
7. Patients with active autoimmune diseases requiring treatment or a known history of uncontrolled autoimmune disorders.
8. Patients with known HIV/AIDS with uncontrolled viral load and cluster of differentiation 4 (CD4) less than 200, a known history of other relevant congenital or acquired immunodeficiencies, or known chronic hepatitis B/C.
9. Patients that have received a live vaccine within 4 weeks of the baseline/screening visit.
10. Use of any of the following ≤ 2 weeks prior to CIVO injection:

    1. Chronic systemic immunosuppressive therapy or corticosteroids. Intranasal, inhaled, topical, or local corticosteroid injections (e.g., intra-articular injection), or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are exceptions to this criterion.
    2. Biological response modifiers for treatment of active autoimmune disease.
    3. Hematopoietic growth factors.
11. Patients with prior treatment with other stimulator of interferon genes (STING) agonist/antagonist and toll-like receptor (TLR) agonists, or cell therapies within 2 months of the baseline/screening visit.
12. Patients receiving concurrent systemic therapy (e.g., chemotherapy, targeted agent, or immunotherapy, etc.) or radiation therapy 4 weeks prior to screening through the planned surgical intervention.