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

NCT03167164 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: QUILT-3.045
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Merkel Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• 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

• Objective response rate by RECIST Version 1.1

  Phase 2 primary endpoint

  1 year

• Objective response rate by irRC

  Phase 2 primary endpoint

  1 year

Secondary Outcomes (9)

• Objective response rate by RECIST Version 1.1

  1 year

• Objective response rate by irRC

  1 year

• Progression-free survival by RECIST Version 1.1

  2 years

• Progression-free survival by irRC

  2 years

• Overall survival

  2 years

Study Arms (1)

NANT MCC Vaccine

EXPERIMENTAL

A combination of agents will be administered to subjects in this study: avelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, leucovorin, nab-paclitaxel, omega-3-acid ethyl esters, stereotactic body radiation therapy, ALT-803, ETBX-051, ETBX-061, GI-6301, and haNK.

Biological: Avelumab; Biological: Bevacizumab; Drug: Capecitabine; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: 5-fluorouracil; Drug: Leucovorin; Drug: nab-Paclitaxel; Drug: omega-3-acid ethyl esters; Radiation: Stereotactic Body Radiation Therapy; Biological: ALT-803; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-6301; Biological: haNK

Interventions

Avelumab BIOLOGICAL

Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

NANT MCC Vaccine

Bevacizumab BIOLOGICAL

Recombinant human anti-VEGF IgG1 monoclonal antibody

NANT MCC Vaccine

Capecitabine DRUG

5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine

NANT MCC Vaccine

Cisplatin DRUG

(SP-4-2)-diamminedichloroplatinum(II)

NANT MCC Vaccine

Cyclophosphamide DRUG

2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate

NANT MCC Vaccine

5-fluorouracil DRUG

5-fluoro-2,4 (1H,3H)-pyrimidinedione

NANT MCC Vaccine

Leucovorin DRUG

Calcium N-\[p-\[\[\[(6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl\]methyl\]amino\]benzoyl\]-L-glutamate (1:1)

NANT MCC Vaccine

nab-Paclitaxel DRUG

5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine

NANT MCC Vaccine

omega-3-acid ethyl esters DRUG

Omega-3-acid ethyl esters

NANT MCC Vaccine

Stereotactic Body Radiation Therapy RADIATION

radiation

NANT MCC Vaccine

ALT-803 BIOLOGICAL

Recombinant human super agonist interleukin-15 (IL-15) complex

NANT MCC Vaccine

ETBX-051 BIOLOGICAL

Ad5 \[E1-, E2b-\]-Brachyury

NANT MCC Vaccine

ETBX-061 BIOLOGICAL

Ad5 \[E1-, E2b-\]-MUC1

NANT MCC Vaccine

GI-6301 BIOLOGICAL

Heat-killed S. cerevisiae yeast expressing the human Brachyury (hBrachyury) oncoprotein

NANT MCC Vaccine

haNK BIOLOGICAL

NK-92 \[CD16.158V, ER IL-2\] (high-affinity activated Natural Killer cells)

NANT MCC Vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Histologically-confirmed metastatic or unresectable MCC with progression on or after anti-PD-L1 therapy (eg, avelumab).
• ECOG performance status of 0 to 2.
• Have at least 1 measurable lesion of ≥ 1.5 cm.
• 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.
• 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.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• 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.

You may not qualify if:

• History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.
• 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.
• 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.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Requires whole blood transfusion to meet eligibility criteria.
• Inadequate organ function, evidenced by the following laboratory results:
• WBC count \< 3,500 cells/mm3.
• Absolute neutrophil count \< 1,500 cells/mm3.
• Platelet count \< 100,000 cells/mm3.
• Hemoglobin \< 9 g/dL.
• Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
• AST (SGOT)) or ALT (SGPT) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).
• Alkaline phosphatase levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases).

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

avelumab; Bevacizumab; Capecitabine; Cisplatin; Cyclophosphamide; Fluorouracil; Leucovorin; 130-nm albumin-bound paclitaxel; Omacor; Radiosurgery; ALT-803

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 25, 2017
• Study Start: December 1, 2017
• Primary Completion: January 1, 2019
• Study Completion: December 28, 2021
• Last Updated: February 21, 2025

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share