Overview

QUILT-3.045: NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After PD-L1 Therapy

Status:
Withdrawn
Trial end date:
2019-03-01
Target enrollment:
0
Participant gender:
All
Summary
This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with MCC who have progressed on or after anti-PD-L1 therapy.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
ImmunityBio, Inc.
NantCell, Inc.
Treatments:
Avelumab
Bevacizumab
Capecitabine
Cisplatin
Cyclophosphamide
Fluorouracil
Leucovorin
Paclitaxel
Vaccines
Criteria
Inclusion Criteria:

1. Age ≥ 18 years.

2. Able to understand and provide a signed informed consent that fulfills the relevant
IRB or IEC guidelines.

3. Histologically-confirmed metastatic or unresectable MCC with progression on or after
anti-PD-L1 therapy (eg, avelumab).

4. ECOG performance status of 0 to 2.

5. Have at least 1 measurable lesion of ≥ 1.5 cm.

6. Must have a recent tumor biopsy specimen obtained following the conclusion of the most
recent anti-cancer treatment. If a historic specimen is not available, the subject
must be willing to undergo a biopsy during the screening period.

7. Must be willing to provide blood samples for exploratory analyses, and if considered
safe by the investigator, a tumor biopsy specimen at 8 weeks after the start of
treatment.

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

9. 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.

Exclusion Criteria:

1. History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity
resulting from previous therapy.

2. History of other active malignancies or brain metastasis except: controlled basal cell
carcinoma; prior history of in situ cancer (eg, breast, melanoma, cervical); prior
history of prostate cancer that is not under active systemic treatment (except
hormonal therapy) and with undetectable PSA (< 0.2 ng/mL); bulky (≥ 1.5 cm) disease
with metastasis in the central hilar area of the chest and involving the pulmonary
vasculature. Subjects with a history of another malignancy must have > 5 years without
evidence of disease.

3. 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.

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

5. History of organ transplant requiring immunosuppression.

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

7. Requires whole blood transfusion to meet eligibility criteria.

8. Inadequate organ function, evidenced by the following laboratory results:

1. WBC count < 3,500 cells/mm3.

2. Absolute neutrophil count < 1,500 cells/mm3.

3. Platelet count < 100,000 cells/mm3.

4. Hemoglobin < 9 g/dL.

5. Total bilirubin greater than the upper limit of normal (ULN; unless the subject
has documented Gilbert's syndrome).

6. AST (SGOT)) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases).

7. Alkaline phosphatase levels > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases, or >10 × ULN in subjects with bone metastases).

8. Serum creatinine > 2.0 mg/dL or 177 μmol/L.

9. INR or aPTT or PTT >1.5 × ULN (unless on therapeutic anti-coagulation).

9. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 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.

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

11. Positive results of screening test for HIV, HBV, or HCV.

12. 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.

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

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

15. Concurrent or prior use of a strong CYP3A4 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.

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

17. Participation in an investigational drug study or history of receiving any
investigational treatment within 14 days prior to screening for this study, except for
testosterone-lowering therapy in men with prostate cancer.

18. Assessed by the investigator to be unable or unwilling to comply with the requirements
of the protocol.

19. Concurrent participation in any interventional clinical trial.

20. Pregnant and nursing women.