14. Where feasible, optional biopsies may be done at baseline and at week 9 and will likely be CT guided. If a recent (≤ 6 months preferred) outside biopsy has been performed that specimen may be used in lieu of a baseline biopsy for both phase I and II participants. 15. Where feasible, research blood (see Section 5.1) will be collected at the following time points: PKs and ADAs – performed only on Arm 1B (bintrafusp alfa plus vaccine) oSamples for PK analysis will be taken prior to infusion and following infusion on W1 and W5 and prior to infusion on W3 and W11 or with end of treatment labs if patients comes off treatment prior to any of those timepoints; and oSamples for ADA analysis will be taken prior to infusion on W1, W5, and W11 or with end of treatment labs if participants come off treatment prior to any of those timepoints. Samples for AVA analysis will be taken prior to infusion on W1, W3, W5, W11, and restaging visits or with end of treatment labs if participants come off treatment prior to any of those timepoints. All other blood samples oBaseline, Week 3, and Week 5; restaging visits per PI discretion. Note: Samples may be sent to Precigen, Inc for additional analyses (see Section 5.1.9). 16. Vital signs at screening should include pulse oximetry on room air. 17. Medical history will include monitoring for signs of bleeding. 18. Skin assessment must be performed at baseline and at least every 6 weeks, starting on week 5 during treatment and at the end of treatment or at the 28 (±7 days) day safety follow-up (if not performed in the previous 6 weeks). 3.4.2 Study Calendar for Phase II ProcedureScreen ing1Baseli ne2Week 1Week 3Week 4-518 EOT4Safety follow up5Long Term follow up6 Treatment 3 X X X NIH Advance Directives Form 7X Medical History 14X Height X Physical exam, weight, vital signs, ECOG 13 X X X X X X X Skin assessment 16X X X X X X HIV, HCV, HepB X EKG X X X CBC with differential X X X X X X X 42 Abbreviated Title: Combo Immunotx in HPV OPSCC Version Date: 04.25.2023 ProcedureScreen ing1Baseli ne2Week 1Week 3Week 4-518 EOT4Safety follow up5Long Term follow up6 Biochemical profile 8X X X X X X X CD4 9X TSH with reflex Free T3 and T4, lipase, amylase, CRPX X X X Urinalysis X Urine or serum pregnancy testing in women of childbearing potential X X X X HLA typing 17X PT, INR, PTT X Tumor evaluation (CT Scan / MRI)10 X X X Concomitant Medications X X X X X X Adverse events X X X X X X Biopsy for immune analysis 11X X Research Blood 12X X X X X Saliva sample 15X X X X X X Taken off treatment for definitive treatment 19 X Telephone/email Follow Up X X 1. Screening evaluations performed within 28 days prior to the first drug administration, unless specified in Section 2.2.