QUILT-3.072: NANT Hepatocellular Carcinoma (HCC) Vaccine

NCT03563170 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: QUILT-3.072
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with advanced, unresectable, and untransplantable HCC.

Conditions

Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Recurrent

Keywords

HCC

Outcome Measures

Primary Outcomes (4)

• Incidence of treatment-emergent AEs and SAEs, graded using the NCI CTCAE Version 4.03

  Phase 1b

  2 years

• Evaluate the overall safety profile in subjects with advanced, unresectable, untransplantable HCC who have progressed or experienced unacceptable toxicity on prior sorafenib treatment. Measured / reported based on the tumor size imaging per RECIST 1.1.

  Phase 1b

  2 years

• Progression Free Survival from baseline to progression, per RECIST 1.1

  Phase 2 Randomized Component

  2 years

• Overall Response Rate, as determined by the percentage of patients achieving Partial or Complete Response per RECIST 1.1

  Phase 2 Single Arm Component

  2 years

Secondary Outcomes (9)

• ORR for Phase 1b and Phase 2 Randomized Component

  2 years

• PFS for Phase 1b and Phase 2 Single Arm Component

  1 year

• OS for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component

  2 years

• DOR for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component

  2 years

• DCR for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component

  1 year

Study Arms (2)

NANT Hepatocellular Carcinoma Vaccine

EXPERIMENTAL

Phase 1b and 2: The following combination of agents will be administered to subjects assigned to this treatment: Aldoxorubicin HCl, ETBX-011, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, N-803, haNK™, avelumab, capecitabine, cetuximab, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, sorafenib tosylate, SBRT.

Biological: ETBX-011; Biological: GI-4000; Biological: haNK for infusion; Biological: avelumab; Drug: Capecitabine; Drug: Cyclophosphamide; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: nab-Paclitaxel; Drug: Sorafenib; Procedure: SBRT; Biological: Aldoxorubicin hydrochloride; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-6207; Biological: GI-6301; Drug: Cetuximab; Biological: N-803

Sorafenib Monotherapy

ACTIVE COMPARATOR

Phase 2: Sorafenib monotherapy will be administered to subjects with advanced, unresectable, and untransplantable HCC, who have not previously received sorafenib, and who are randomly assigned to receive SOC treatment.

Drug: Sorafenib

Interventions

ETBX-011 BIOLOGICAL

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

NANT Hepatocellular Carcinoma Vaccine

GI-4000 BIOLOGICAL

Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant RAS proteins

NANT Hepatocellular Carcinoma Vaccine

haNK for infusion BIOLOGICAL

NK-92 \[CD16.158V, ER IL-2\]

NANT Hepatocellular Carcinoma Vaccine

avelumab BIOLOGICAL

Recombinant human anti-PD-L1 IgG1 monoclonal antibody

NANT Hepatocellular Carcinoma Vaccine

Capecitabine DRUG

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

NANT Hepatocellular Carcinoma Vaccine

Cyclophosphamide DRUG

anhydrous

NANT Hepatocellular Carcinoma Vaccine

5-Fluorouracil DRUG

5-FU; Fluorouracil

NANT Hepatocellular Carcinoma Vaccine

Leucovorin DRUG

Leucovorin calcium salt

NANT Hepatocellular Carcinoma Vaccine

nab-Paclitaxel DRUG

ABRAXANE® \[paclitaxel protein-bound particles for injectable suspension\] \[albumin-bound\]

NANT Hepatocellular Carcinoma Vaccine

Sorafenib DRUG

NEXAVAR® tablets, for oral use

NANT Hepatocellular Carcinoma Vaccine; Sorafenib Monotherapy

SBRT PROCEDURE

Stereotactic Body Radiation Therapy

NANT Hepatocellular Carcinoma Vaccine

Aldoxorubicin hydrochloride BIOLOGICAL

HCl

NANT Hepatocellular Carcinoma Vaccine

ETBX-051 BIOLOGICAL

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

NANT Hepatocellular Carcinoma Vaccine

ETBX-061 BIOLOGICAL

Ad5 \[E1-, E2b-\]-mucin 1 \[MUC1\] vaccine

NANT Hepatocellular Carcinoma Vaccine

GI-6207 BIOLOGICAL

CEA yeast vaccine

NANT Hepatocellular Carcinoma Vaccine

GI-6301 BIOLOGICAL

Brachyury yeast vaccine

NANT Hepatocellular Carcinoma Vaccine

Cetuximab DRUG

ERBITUX® injection, for IV infusion)

NANT Hepatocellular Carcinoma Vaccine

N-803 BIOLOGICAL

Recombinant human super agonist IL-15 complex \[also known as IL-15N72D:IL- 15RαSu/IgG1 Fc complex\]

NANT Hepatocellular Carcinoma 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 Independent Ethics Committee (IEC) guidelines.
• Histologically-confirmed advanced, unresectable and untransplantable HCC.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have at least 1 measurable lesion of ≥ 1.0 cm.
• Must have Child-Pugh class A only.
• 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.
• Must be willing to provide blood samples prior to the start of treatment on this study for prospective tumor molecular profiling and exploratory analyses.
• 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.
• 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. 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.
• Any prior locoregional therapy allowed.
• Phase 1b only
• Must have progressed or experienced unacceptable toxicity on sorafenib prior to enrollment in the study.
• Phase 2 single-arm component only

You may not qualify if:

• 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, or autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count \< 1,000 cells/mm\^3
• Medically uncorrectable grade 3 anemia (hemoglobin \< 8 g/dL).
• Platelet count \< 75,000 cells/mm\^3.
• Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
• Aspartate aminotransferase (AST \[SGOT\]) or alanine aminotransferase (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).
• Serum creatinine \> 2.0 mg/dL or 177 μmol/L.
• International normalized ratio (INR) ≥ 2.0
• Serum anion gap \> 16 mEq/L or arterial blood with pH \< 7.3.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (1)

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

Location

MeSH Terms

Interventions

avelumab; Capecitabine; Cyclophosphamide; Fluorouracil; Leucovorin; 130-nm albumin-bound paclitaxel; Sorafenib; yeast-CEA vaccine; Cetuximab; ALT-803

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; 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; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

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

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: June 20, 2018
• Study Start: May 25, 2018
• Primary Completion: August 23, 2019
• Study Completion: August 23, 2019
• Last Updated: March 18, 2021

Record last verified: 2018-10

Locations

US (1)