A Phase 1, Multicenter, Open-Label Study of SQZ-AAC-HPV as
Monotherapy and in Combination with Immune Checkpoint
Inhibitors in HLA-A*02+ Patients with HPV16+ Recurrent, Locally
Advanced or Metastatic Solid Tumors

1. Male or female patients *18 years of age who are HLA-A*02+, as confirmed by
genotyping assay from blood.
2. Histologically confirmed incurable or metastatic solid tumors (including but
not limited anal, to cervical and head and neck tumors) that are HPV16+.
3. For cervical cancer, which is not amenable to curative treatment with
surgery, radiation, and/or chemoradiation therapy, the cancer must have
progressed after prior systemic chemotherapeutic treatment with a
platinum-based regimen in the adjuvant or recurrent setting. Patients must have
progressive disease (PD) while receiving or after the completion of the most
recent prior treatment.
4. For recurrent and metastatic head and neck cancer, which is not amenable to
curative treatment with surgery, radiation, and/or chemoradiation therapy, the
cancer must have progressed following at least 1 prior platinum-based
chemotherapy in the primary, adjuvant, or recurrent setting and been offered
checkpoint immunotherapy. Patients who relapsed after platinum-containing
definitive chemoradiation or after adjuvant chemoradiation are eligible if a
platinum re-challenge at time of relapse is not seen as beneficial.
5. Patients with incurable or metastatic HPV16+ cancers other than cervical or
head and neck cancer must have progressed after at least 1 available standard
therapy for incurable disease, or the patient is intolerant to or refuses
standard therapy(ies) or has a tumor for which no standard therapy(ies) exist.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
7. Patients must agree to venous access for the blood collection for
manufacture of autologous blood product and be willing to have a central line
inserted if venous access is an issue.
8. Patients with unresectable or metastatic solid tumors must have a lesion
that can be biopsied with acceptable clinical risk and agree to have a fresh
biopsy at Screening and on Cycle 2 Day 8 (±2 days). The second biopsy must be
taken from the same lesion of the biopsy at Screening.
9. At least 1 measurable lesion according to RECIST 1.1.
10. Adequate organ function and bone marrow reserve as indicated by the
following laboratory assessments performed within 14 days prior to the blood
collection for manufacture of autologous blood product:
a. Bone marrow function: absolute neutrophil count *1000/µL; hemoglobin *9
g/dL; platelet count *75,000/µL.
b. Hepatic function: total serum bilirubin *1.5 × ULN; serum AST/ALT, *2.5 ×
ULN (*5 × ULN in the presence of hepatic metastases); alkaline phosphatase
<2.5 × ULN with the following exception: patients with liver and bone
involvement: alkaline phosphatase *5 × ULN.
c. Renal function: serum creatinine *2.5 × ULN or creatinine clearance *30
mL/min based either on urine collection or Cockcroft-Gault estimation.
d. Coagulation profile: prothrombin time (PT), international normalized ratio
(INR)/partial thromboplastin time (PTT) *1.5 × ULN. Patients on a stable,
maintenance regimen of anticoagulant therapy for at least 30 days prior to
blood collection for manufacture of autologous blood product may have PT/INR
measurements >1.5 × ULN if, in the opinion of the Investigator, the patient
is suitable for the study. An adequate rationale must be provided to the
Sponsor prior to enrollment.
11. Patients with immune-mediated endocrinopathies following treatment with
immune checkpoint inhibitors requiring hormone replacement therapy are eligible.
a. Patients requiring prednisone as part of hormone replacement therapy are
eligible if the daily doses do not exceed 10 mg.
12. Female patients of childbearing potential must:
a. Have a negative serum beta human chorionic gonadotropin (*-hCG) pregnancy
test at Screening, and
b. Agree to use highly effective contraception from the time of informed
consent until at least 5 months after the last dose of immune checkpoint
inhibitor or SQZ AAC-HPV (CTFG, 2020).
13. Male patients who are not vasectomized must be willing to use condoms from
the time of informed consent until at least 5 months after the last dose of
immune checkpoint inhibitor or SQZ AAC HPV.
14. The patient is capable of understanding and complying with the protocol and
has signed the required informed consent form (ICF). The appropriate ICF must
be signed before relevant study procedures are performed. If applicable, the
female partner of a male patient understands and signs the pregnant partner
ICF.

1. Treatment with anticancer therapy, including investigational therapy, within
2 weeks prior to blood collection for manufacture of autologous blood product.
For prior therapies with a half-life longer than 3 days, timing of
discontinuation of the therapy should be discussed with Sponsor.
2. Patients with >Grade 1 AEs (except Grade 2 alopecia) according to NCI CTCAE
version 5.0 related to previous treatment with anticancer or investigational
therapy that do not resolve (ie, to >Grade 2) at least 2 weeks prior to blood
collection for manufacture of autologous blood product.
3. History of any Grade 4 irAE from prior immunotherapy (patients with
endocrinopathy managed with replacement therapy or asymptomatic elevation of
serum amylase or lipase are eligible), any irAE that led to permanent
discontinuation of prior immunotherapy, or any Grade 3 irAE that occurred *6
months prior to blood collection for manufacture of autologous blood product.
4. Patients treated with non-corticosteroid based immunosuppressive agents
within the last 6 months may not be eligible and should be discussed with
Sponsor.
5. Patients with active, known, or suspected autoimmune disease may not be
eligible and should be discussed with Sponsor.
6. Patients who have undergone splenectomy.
7. Patients who have received or who are anticipated to require blood
transfusion within 4 weeks prior to the blood draw for autologous
investigational product manufacture.
8. Patients with prior allogeneic bone marrow or solid organ transplantation
may not be eligible and should be discussed with Sponsor.
9. Live virus vaccination within 4 weeks prior to blood collection for
manufacture of autologous blood product.
10. Systemic treatment with either corticosteroids (>10 mg of prednisone or the
equivalent per day) or other immunosuppressive medications within 14 days prior
to blood collection for manufacture of autologous blood product.
11. Known active central nervous system metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate
provided they are stable (without evidence of progression by imaging for at
least 4 weeks prior to the first dose of investigational product and any
neurologic symptoms have returned to Baseline), have no evidence of new or
enlarging brain metastases, and are not using steroids for at least 7 days
prior to blood collection for manufacture of autologous blood product. This
exception does not include carcinomatous meningitis, which is excluded
regardless of clinical status.
12. History of interstitial lung disease requiring steroids, idiopathic
pulmonary fibrosis, pneumonitis (including drug induced), or organizing
pneumonia (eg, bronchiolitis obliterans, cryptogenic organizing pneumonia).
13. Clinically significant cardiac disease, including unstable angina, acute
myocardial infarction within 6 months prior to blood collection for manufacture
of autologous blood product, New York Heart Association class III or IV
congestive heart failure, and arrhythmia requiring therapy.
14. Systemic arterial thrombotic or embolic events, such as cerebrovascular
accident (including ischemic attacks) within 1 month prior to blood collection
for manufacture of autologous blood product.
15. Systemic venous thrombotic events (eg, deep vein thrombosis) or pulmonary
arterial events (eg, pulmonary embolism) within 1 month prior to blood
collection for manufacture of autologous blood product.
16. History or presence of an abnormal ECG that, in the Investigator*s opinion,
is clinically meaningful.
17. Left ventricular ejection fraction (LVEF) <50%.
18. Major surgery within 2 weeks of blood collection for manufacture of
autologous blood product; following major surgeries >2 weeks prior to blood
collection for manufacture, all surgical wounds must be healed and free of
infection or dehiscence.
19. Any other clinically significant comorbidities, such as active infection,
known psychiatric or neurological disorder, or any other condition, which in
the judgment of the Investigator, could compromise compliance with the
protocol, interfere with the interpretation of study results, or predispose the
patient to safety risks.
20. Known active hepatitis B or hepatitis C, or active mycobacterium
tuberculosis infection.
21. History of alcohol and/or illicit drug abuse within 12 months of entry.
22. Female patients who are breastfeeding or have a positive serum pregnancy
test at the Screening visit.
23. History of allergy or hypersensitivity to any component of SQZ AAC HPV.
24. History of severe allergic anaphylactic reactions to chimeric, human, or
humanized antibodies or infusion proteins (combination cohorts only).
25. Known hypersensitivity to ipilimumab, nivolumab, Chinese hamster ovary cell
products, or any component of the ipilimumab or nivolumab formulation
(combination cohorts only).
26. Enrollment of HIV+ patients should be discussed with Sponsor.