PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592 in HNSCC

Inclusion Criteria:

1. Ability and willingness to provide written informed consent. Voluntary writtenconsent must be given before performance of any study related procedure not part ofstandard medical care, with the understanding that consent may be withdrawn by thepatient at any time without prejudice to future medical care.

2. Male or female ≥ 18 years of age at Visit 1 (Screening).

3. Pathologic diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC) of theoropharynx, hypopharynx, oral cavity, or larynx.

4. Ability and willingness to comply with the study's visits and assessment schedule.

5. At least one lesion (primary tumor, recurrent tumor, metastasis, or metastatic lymphnode) that is surface accessible for CIVO injection that contains viable minimumtumor tissue volume and characteristics (e.g., based on clinical evaluation,available pre-operative imaging, pre-injection ultrasound imaging, or pathologyreports indicating lesion with appropriate viable tumor volume without excessivecysts or necrosis) and for which there is a planned surgical intervention. Thepatient's presentation, surgical and pathology plan may determine whether a lesionis eligible with respect to a given CIVO MID needle configuration.

6. Eastern Cooperative Oncology Group (ECOG) performance status 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 methodof contraception from the time of signing the Informed Consent Form (ICF) until 7 months after the CIVO injection OR agree to completely abstain fromheterosexual intercourse.

• Agree to refrain from donating, or retrieving for their own use, ova until 7months after the CIVO injection.

• Agree to refrain from breastfeeding until 7 months after the CIVO injection.

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

• Agree to practice effective barrier contraception from the time of signing theICF until 7 months after the CIVO injection OR agree to completely abstain fromheterosexual intercourse.

• Agree to refrain from fathering a child or donating sperm until 7 months afterthe CIVO injection.

Exclusion Criteria:

1. Tumors and/or effaced nodes that are anticipated by the Investigator to lack asufficient volume of viable tumor tissue (Based on available pre-operative imaging,pre-injection ultrasound imaging, or pathology reports) for CIVO microdose injectiondue to necrosis, cysts, excessive stroma, fibrosis, or treatment-induced tissuechanges.

2. Tumors near or involving critical structures for which, in the opinion of thetreating clinician, injection would pose undue risk to the patient.

3. Prior exposure to immune-mediated therapy including, but not limited to, otheranti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies within the last 5years.

4. Previous treatment with another ADC containing a chemotherapeutic agent thatinhibits topoisomerase 1 activity or with another epidermal growth factor receptor (EGFR) and/or mesenchymal-epithelial transition factor (c-MET) targeted ADC.

5. Patients with concurrent cancer, immune disease or active infection requiringsystemic or radiotherapy.

6. Female patients who:

• Intend to become pregnant during the study,

• Are both lactating and breastfeeding, OR

• Have a positive beta-subunit human chorionic gonadotropin (beta-hCG) pregnancytest at screening verified by the Investigator.

7. Any uncontrolled intercurrent illness, condition, serious medical or psychiatricillness, or circumstance that, in the opinion of the Investigator, could interferewith adherence to the study's procedures or requirements, or otherwise compromisethe study's objectives.

8. History of organ transplant.

9. Major surgery within 4 weeks prior to injection: subject must have adequate woundhealing and have recovered from any prior surgery.