A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers

A Phase I/II Study of TheraT® Vector(s) Expressing Human Papillomavirus 16 Positive (HPV 16+) Specific Antigens in Patients With HPV 16+ Confirmed Cancers

This is a First in Human (FIH) Phase I/II, multinational, multicenter, open-label study of HB-201 single vector therapy and HB-201 & HB-202 two-vector therapy in patients with HPV 16+ confirmed cancers comprising two parts: Phase I Dose Escalation and Phase II Dose Expansion.

HB-201 and HB-202 are study drugs which are designed to train the body to recognize and fight substances found in HPV 16+ cancer. This trial studies the safety and anti-cancer effect of HB-201 and HB-202 in people.

The trial is enrolling patients with metastatic/recurrent head and neck cancer who have not yet received treatment in this setting (1L, first line) and who are eligible to receive pembrolizumab as part of their standard of care. This trial is also enrolling patients with metastatic/recurrent head and neck who have received prior treatment in this setting (2L+, second and later line) who are eligible to receive pembrolizumab as part of their standard of care. Patients will receive the study drugs in addition to their pembrolizumab standard of care regimen.

Inclusion Criteria

All Patients:

• Documentation of confirmed HPV 16+ cancer via genotype testing.
• ≥ 1 measurable lesion by imaging for tumor response following RECIST
• ECOG performance status of 0 to 1.
• Prior curative radiation therapy and prior focal palliative completed per protocol-specified wash-out windows.
• Screening laboratory values must meet protocol-specified criteria.
• Able to provide tumor tissue following last treatment, unless otherwise agreed.

Treatment Group E or Group F:

• Documentation of confirmed head and neck squamous cell carcinoma.
• Eligible to receive pembrolizumab, per standard of care and product label.
• Group E: this group includes first line / 1L patients who have not yet received treatment in the metastatic/recurrent setting.
• Group F: Tumor progression or recurrence on standard of care therapy, including ≥1 systemic therapy.

Imaging Sub-Study (for specific participants at Memorial Sloan Kettering Cancer Center only):

• Meeting requirements of inclusion criteria for Treatment Group 1 or Group 3.
• At least 1 non-irradiated measurable lesion documented through imaging.

Exclusion Criteria:

All patients:

• Metastatic central nervous system disease, and/or carcinomatous meningitis.
• Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation / treatment administration.
• Concurrent malignancy that is clinically significant or requires active intervention, unless protocol-defined criteria are met.
• Active, known or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy.
• Has a life expectancy of less than 3 months.
• Any toxicities attributed to systemic prior anticancer therapy o that have not resolved to Grade 1 or baseline prior to the first administration of study drug, unless protocol-defined criteria is met.
• Not meeting the protocol-specified washout periods for prohibited medications.
• Prior anaphylactic reaction to or known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
• Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody, indicating acute or chronic infection.
• Known history of acquired immunodeficiency syndrome.

For patients in Groups E or F and certain backfill cohorts:

• History of severe hypersensitivity reaction to or other contraindication to receiving pembrolizumab.
• History of/Presently having non-infectious pneumonitis requiring treatment.
• Was discontinued due to a Grade 3 or higher immune-related AE (irAE) after receiving prior therapy with check point inhibitors.

Imaging Sub-Study (for specific participants at Memorial Sloan Kettering Cancer Center only):

• Having splenic disorders or prior splenectomy, and can compromise protocol objectives per Investigator and/or Sponsor.
• Meeting requirements of exclusion criteria for Treatment Group 3