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Hepatocellular Carcinoma Non-resectablePhase 1/2NCT03563170

QUILT-3.072: NANT Hepatocellular Carcinoma (HCC) Vaccine

A Phase 1/2 study testing ETBX-011, GI-4000 and haNK for infusion in people with Hepatocellular Carcinoma Non-resectable and Hepatocellular Carcinoma Recurrent, run by ImmunityBio, Inc. at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ETBX-011, GI-4000 and haNK for infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
25 May 2018to 23 Aug 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Must have progressed on or after sorafenib monotherapy in the randomized phase 2 portion of the study OR progressed or experienced unacceptable toxicity on sorafenib prior to enrollment on the study.

Who cannot join

  • 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
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  • 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.
  • 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.
  • Episode of portal hypertension-related GI bleeding within prior 6 months.
  • Serious myocardial dysfunction defined by echocardiogram (ECHO) as absolute left ventricular ejection fraction (LVEF) 10% below the institution's lower limit of normal (LLN).
  • Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
  • Positive results of screening test for human immunodeficiency virus (HIV).
  • Participants with dual active hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg] positive [+] and /or detectable HBVDNA) and hepatitis C virus (HCV) infection (anti-HCV antibody [Ab] [+] and detectable HCV ribonucleic acid [RNA]) at study entry. Subjects with chronic infection by HCV who are treated with anti-hepatitis B therapy (successfully or treatment failure) or untreated are allowed on study. Controlled (treated) hepatitis B subjects will be allowed if they meet the following criteria:
  • Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug; subjects on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment.
  • Subjects who are positive for anti-hepatitis B core Abs (HBc[+]), negative for HBsAg, negative for anti-hepatitis B surface Ab (HBs[-]), and have a HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.
  • Subjects with successful HCV treatment are allowed as long as there are at least 4 weeks between achieving sustained viral response (SVR) and start of study drug.
  • 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.
  • Known hypersensitivity to any component of the study medication(s).
  • Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
  • 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.
  • Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
  • 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.
  • Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
  • Concurrent participation in any interventional clinical trial.
  • Pregnant and nursing women.
  • Phase 2 randomized component only -
  • Prior sorafenib treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Chan Soon-Shiong Institute for Medicine

    El Segundo, California, 90245

Other trials in United States

About this study

Official title: Molecularly Informed Integrated Immunotherapy Combining Innate High-affinity Natural Killer (haNK) Cell Therapy w/ Adenoviral & Yeast-based Vaccines to Induce T-cell Responses in Subjects w/ Advanced, Unresectable & Untransplantable HCC

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.

Read the detailed description

Treatment will be administered in two phases, an induction and a maintenance phase. Subjects will continue induction treatment for up to 1 year. Those who have a CR in the induction phase will enter the maintenance phase of the study. Subjects who experience ongoing SD or an ongoing 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. Treatment in the study will be discontinued if the subject experiences confirmed PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, undergoes liver transplantation or surgical resection, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Subjects with an initial assessment of PD may, at the discretion of the Investigator, continue to receive study treatment until PD is confirmed. The maximum time on study treatment is 2 years.

Being tested
ETBX-011, GI-4000, haNK for infusion, avelumab, Capecitabine
Keywords
HCC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ETBX-011Biological

    Ad5 [E1-, E2b-]-CEA

  • GI-4000Biological

    Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant RAS proteins

  • haNK for infusionBiological

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

  • avelumabBiological

    Recombinant human anti-PD-L1 IgG1 monoclonal antibody

  • CapecitabineDrug

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

  • CyclophosphamideDrug

    anhydrous

  • 5-FluorouracilDrug

    5-FU; Fluorouracil

  • LeucovorinDrug

    Leucovorin calcium salt

  • nab-PaclitaxelDrug

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

  • SorafenibDrug

    NEXAVAR® tablets, for oral use

  • SBRTProcedure or surgery

    Stereotactic Body Radiation Therapy

  • Aldoxorubicin hydrochlorideBiological

    HCl

  • ETBX-051Biological

    Ad5 [E1-, E2b-]-Brachyury vaccine

  • ETBX-061Biological

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

  • GI-6207Biological

    CEA yeast vaccine

  • GI-6301Biological

    Brachyury yeast vaccine

  • CetuximabDrug

    ERBITUX® injection, for IV infusion)

  • N-803Biological

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

Study groups in NCT03563170
Study groupRoleWhat they receive
NANT Hepatocellular Carcinoma VaccineExperimentalPhase 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.
Receives: 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 MonotherapyActive comparatorPhase 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.
Receives: Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Phase 1b

    Measured: 2 years

  2. 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

    Measured: 2 years

  3. Progression Free Survival from baseline to progression, per RECIST 1.1

    Phase 2 Randomized Component

    Measured: 2 years

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

    Phase 2 Single Arm Component

    Measured: 2 years

Secondary outcomes (9)

  1. ORR for Phase 1b and Phase 2 Randomized Component

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

    Measured: 2 years

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

    Progression Free Survival from baseline to progression per RECIST 1.1 and irRC

    Measured: 1 year

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

    Overall Survival from first treatment to date of death (any cause)

    Measured: 2 years

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

    Duration of Response from date of first response to date of disease progression or death (any cause), per RECIST 1.1 and irRC

    Measured: 2 years

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

    Disease Control Rate: the number of patients with a CR, PR or SD lasting at least 2 months per RECIST 1.1 and irRC

    Measured: 1 year

  6. QoL for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component

    Quality of Life as assessed by Patient Reported Outcomes using the FACT-C questionnaire

    Measured: 1 year

  7. PFS for Phase 2 Randomized Component

    Progression Free Survival from baseline to progression per irRC

    Measured: 2 years

  8. Safety for Phase 2 Randomized and Single Arm Component

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

    Measured: 2 years

  9. ORR for Phase 2 Single Arm Component

    Overall Response Rate, as determined by the percentage of patients achieving Partial or Complete response per irRC

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2018
  2. Study start25 May 2018
  3. Primary completion23 Aug 2019
  4. Study completion23 Aug 2019

Why it stopped: Enrollment not initiated

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03563170
Sponsor's protocol ID
QUILT-3.072
Status last verified
Oct 2018
First submitted
22 May 2018
Last updated
18 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ETBX-011, GI-4000 and haNK for infusion in people with Hepatocellular Carcinoma Non-resectable and Hepatocellular Carcinoma Recurrent, run by ImmunityBio, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 18 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-emergent AEs and SAEs, graded using the NCI CTCAE Version 4.03 (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03563170.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2021.

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