QUILT-3.091 NANT Chordoma Vaccine vs Radiation in Subjects With Unresectable Chordoma.

The NANT Chordoma Vaccine regimen will be administered in 2 phases, an induction and a
maintenance phase.

Subjects will continue induction treatment for up to 1 year. Those who have a confirmed
complete response (CR) in the induction phase will enter the maintenance phase of the study.
Subjects who experience ongoing stable disease (SD) or an ongoing partial response (PR) at 1
year may enter the maintenance phase at the Investigator's and Sponsor's discretion. Subjects
may remain in the maintenance phase of the study for up to 1 year.

In the randomized component of the phase 2 portion of the study, the control arm will be
treated with radiation according to established SoC protocols as determined by the
Investigator.

In the phase 2 single-arm component of the study, subjects will be enrolled in the first
stage of Simon's two-stage optimal design. If the study proceeds to the second stage of
Simon's two-stage optimal design, additional subjects will be enrolled in the second stage.

Inclusion Criteria:

1. Age ≥ 18 years.

2. Able to understand and provide a signed informed consent that fulfills the relevant
IRB or Independent Ethics Committee (IEC) guidelines.

3. Histologically-confirmed recurrent or unresectable chordoma that would require
radiation as a primary means for treatment.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. Have at least 1 measurable lesion of ≥ 1.0 cm.

6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen
following the conclusion of the most recent anticancer treatment and be willing to
release the specimen for prospective and exploratory tumor molecular profiling. If an
historic specimen is not available, the subject must be willing to undergo a biopsy
during the screening period, if considered safe by the Investigator. If safety
concerns preclude collection of a biopsy during the screening period, a tumor biopsy
specimen collected prior to the conclusion of the most recent anticancer treatment may
be used.

7. Must be willing to provide blood samples prior to the start of treatment on this study
for tumor molecular profiling and exploratory analyses.

8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of
treatment for exploratory analyses, if considered safe by the Investigator.

9. Ability to attend required study visits and return for adequate follow-up, as required
by this protocol.

10. Agreement to practice effective contraception for female subjects of child-bearing
potential and non-sterile males. Female subjects of child-bearing potential must agree
to use effective contraception for up to 1 year after completion of therapy, and non-
sterile male subjects must agree to use a condom for up to 4 months after treatment.
Effective contraception includes surgical sterilization (eg, vasectomy, tubal
ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide,
intrauterine devices (IUDs), and abstinence.

Randomized component only - 11. Must be able to be classified into at least 1 of the below
3 categories: i. Recurred within 6 months after treatment, ii. Have metastatic disease,
iii. Meet ≥ 4 of the histopathologic and immunohistochemical criteria: • Poorly
differentiated histopathologic sub type, • Mitotic figures ≥ 3, • Apoptosis present. •
Prominent nucleoli present, • Necrosis present, • Ki67 ≥ 6%, • p53 ≥ 25%

Single-arm component only 12. Must have progressed on or after radiation monotherapy in the
randomized portion of the study OR been ineligible for the randomized portion but had
progressed or experienced unacceptable toxicity on SoC prior to enrollment on the study.

Exclusion Criteria:

1. Serious uncontrolled concomitant disease that would contraindicate the use of the
investigational drug used in this study or that would put the subject at high risk for
treatment-related complications.

2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis,Addison's
disease, or autoimmune disease associated with lymphoma).

3. History of organ transplant requiring immunosuppression.

4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis).

5. Inadequate organ function, evidenced by the following laboratory results: a. Absolute
neutrophil count < 1,000 cells/mm^3, b. Uncorrectable grade 3 anemia (hemoglobin < 8
g/dL), c. Platelet count < 75,000 cells/mm^3, d. Total bilirubin greater than the
upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome), e.
Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5
× ULN (> 5 × ULN in subjects with liver metastases), f. Alkaline phosphatase levels >
2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with
bone metastases), g. Serum creatinine > 2.0 mg/dL or 177 μmol/L, h. Serum anion gap >
16 mEq/L or arterial blood with pH < 7.3.

6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
clinically significant (ie, active) cardiovascular disease, cerebrovascular
accident/stroke, or myocardial infarction within 6 months prior to first study
medication; unstable angina; congestive heart failure of New York Heart Association
grade 2 or higher; or serious cardiac arrhythmia requiring medication. Subjects with
uncontrolled hypertension should be medically managed on a stable regimen to control
hypertension prior to study entry.

7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection
fraction (LVEF) 10% below the institution's lower limit of predicted normal.

8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
continuous oxygen therapy.

9. Positive results of screening test for human immunodeficiency virus (HIV).

10. Current chronic daily treatment (continuous for > 3 months) with systemic
corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
reaction or anaphylaxis in subjects who have known contrast allergies is allowed.

11. Known hypersensitivity to any component of the study medication(s).

12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
reaction with any of the study medications.

13. Concurrent or prior use of a strong cytochrome P450 (CYP)3A4 inhibitor (including
ketoconazole, itraconazole, posaconazole, clarithromycin, indinavir, nefazodone,
nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, and grapefruit
products) or strong CYP3A4 inducers (including phenytoin, carbamazepine, rifampin,
rifabutin, rifapentin, phenobarbital, and St John's Wort) within 14 days before study
day 1.

14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8
inducer (rifampin) within 14 days before study day 1.

15. Participation in an investigational drug study or history of receiving any
investigational treatment within 30 days prior to screening for this study, except for
testosterone- lowering therapy in men with prostate cancer.

16. Assessed by the Investigator to be unable or unwilling to comply with the requirements
of the protocol.

17. Concurrent participation in any interventional clinical trial.

18. Pregnant and nursing women.