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

Merkel Cell Carcinoma Clinical Trial

Official title:

NANT Merkel Cell Carcinoma (MCC) Vaccine: Combination Immunotherapy in Subjects With MCC Who Have Progressed on or After Anti-programmed Death-ligand 1 (PD-L1) Therapy

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03167164
• Other study ID #: QUILT-3.045
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: December 2017
• Est. completion date: March 2019

Study information

• Verified date: October 2017
• Source: ImmunityBio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Treatment will be administered in two phases. Subjects will continue treatment until they experience progressive disease (PD) or experience unacceptable toxicity (not correctable with dose reduction), withdraw consent, or if the investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) will enter phase 2 of the study. Subjects may remain on phase 2 of the study for up to 1 year. Treatment will continue in phase 2 until the subject experiences PD or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the investigator feels it is no longer in the subject's best interest to continue treatment.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Merkel Cell
• Merkel Cell Carcinoma

Intervention

Biological:
• Avelumab
Fully human anti-PD-L1 IgG1 lambda monoclonal antibody
• Bevacizumab
Recombinant human anti-VEGF IgG1 monoclonal antibody

Drug:
• Capecitabine
5'-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
• Cisplatin
(SP-4-2)-diamminedichloroplatinum(II)
• Cyclophosphamide
2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
• 5-fluorouracil
5-fluoro-2,4 (1H,3H)-pyrimidinedione
• Leucovorin
Calcium N-[p-[[[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl]methyl]amino]benzoyl]-L-glutamate (1:1)
• nab-Paclitaxel
5ß,20-Epoxy-1,2a,4,7ß,10ß,13a-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine
• omega-3-acid ethyl esters
Omega-3-acid ethyl esters

Radiation:
• Stereotactic Body Radiation Therapy
radiation

Biological:
• ALT-803
Recombinant human super agonist interleukin-15 (IL-15) complex
• ETBX-051
Ad5 [E1-, E2b-]-Brachyury
• ETBX-061
Ad5 [E1-, E2b-]-MUC1
• GI-6301
Heat-killed S. cerevisiae yeast expressing the human Brachyury (hBrachyury) oncoprotein
• haNK
NK-92 [CD16.158V, ER IL-2] (high-affinity activated Natural Killer cells)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ImmunityBio, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03.	Phase 1b primary endpoint	1 year
Primary	Objective response rate by RECIST Version 1.1	Phase 2 primary endpoint	1 year
Primary	Objective response rate by irRC	Phase 2 primary endpoint	1 year
Secondary	Objective response rate by RECIST Version 1.1	Phase 1b secondary endpoint	1 year
Secondary	Objective response rate by irRC	Phase 1b secondary endpoint	1 year
Secondary	Progression-free survival by RECIST Version 1.1	Phase 1b and Phase 2 secondary endpoint	2 years
Secondary	Progression-free survival by irRC	Phase 1b and Phase 2 secondary endpoint	2 years
Secondary	Overall survival	Phase 1b and Phase 2 secondary endpoint	2 years
Secondary	Duration of response	Phase 1b and Phase 2 secondary endpoint	2 years
Secondary	Disease control rate (confirmed complete response, partial response, or stable disease lasting for at least 2 months)	Phase 1b and Phase 2 secondary endpoint	2 years
Secondary	Quality of life by patient-reported outcome using Functional Assessment of Cancer Therapy-Melanoma (FACT-M) Questionnaire	Phase 1b and Phase 2 secondary endpoint	2 years
Secondary	Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03	Phase 2 secondary endpoint	1 year