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Urothelial CarcinomaPhase 1/2NCT03197571

QUILT-3.048: NANT Urothelial Cancer Vaccine: Combination Immunotherapy in Subjects With Urothelial Cancer Who Have Progressed on or After Chemotherapy and PD-1/PD-L1 Therapy

A Phase 1/2 study testing avelumab, bevacizumab and capecitabine in people with Urothelial Carcinoma, run by ImmunityBio, Inc..

Withdrawn

Withdrawn.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 urothelial cancer who have progressed on or after chemotherapy and anti- PD-1/PD-L1 therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
avelumab, bevacizumab and capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2017to 28 Dec 2021
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 urothelial cancer with progression on or after chemotherapy and anti-PD-1/PD-L1 therapy.
  • Eastern Cooperative Oncology Group (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 anticancer treatment. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
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  • Must be willing to provide blood samples 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.

Who cannot join

  • History of persistent grade 2 or higher (CTCAE Version 4.03) hematologic toxicity resulting from previous therapy.
  • Within 5 years prior to first dose of study treatment, any evidence 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 prostate-specific antigen (PSA) (< 0.2 ng/mL); and bulky (≥ 1.5 cm) disease with metastasis in the central hilar area of the chest and involving the pulmonary vasculature.
  • 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).
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  • Requires whole blood transfusion to meet eligibility criteria.
  • Inadequate organ function, evidenced by the following laboratory results:
  • White blood cell (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).
  • Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
  • Alkaline phosphatase (ALP) 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) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic anti-coagulation).
  • 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.
  • 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), hepatitis B virus (HBV), or hepatitis C virus (HCV).
  • 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.

About this study

Official title: QUILT-3.048: NANT Urothelial Cancer Vaccine: Combination Immunotherapy in Subjects With Urothelial Cancer Who Have Progressed on or After Chemotherapy and Anti-programmed Cell Death Protein 1 (PD-1)/Programmed Death-ligand 1 (PD-L1) Therapy

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with urothelial cancer who have progressed on or after chemotherapy and anti- PD-1/PD-L1 therapy.

Read the detailed description

The initial 3 subjects will be enrolled in a staggered fashion, with a 21-day interval between each subject to enable the assessment of any acute and subacute toxicities, unless data are available from other NANT cancer vaccine studies suggesting the combination therapy is tolerable.

Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (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. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase 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.

Medical subject headings
Carcinoma, Transitional Cell

What participants receive

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

  • avelumabBiological

    Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

  • bevacizumabBiological

    Recombinant human anti-vascular endothelial growth factor (VEGF) IgG1 monoclonal antibody

  • capecitabineDrug

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

  • cisplatinDrug

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

  • cyclophosphamideDrug

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

  • 5Fluorouracil (5-FU)Drug

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

  • fulvestrantDrug

    7-alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl) nonyl]estra-1,3,5-(10)- triene-3,17-beta-diol

  • leucovorinDrug

    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-paclitaxelDrug

    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

  • LovazaDrug

    Omega-3-acid ethyl esters

  • Stereotactic Body Radiation TherapyRadiation

    (SBRT)

  • ALT-803Biological

    recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex]

  • ETBX-011Biological

    adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] vaccine

  • ETBX-021Biological

    Ad5 [E1-, E2b-]-human epidermal growth factor receptor 2 [HER2] vaccine

  • ETBX-051Biological

    Ad5 [E1-, E2b-]-Brachyury vaccine

  • ETBX-061Biological

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

  • GI-4000Biological

    RAS yeast vaccine

  • GI-6207Biological

    CEA yeast vaccine

  • GI-6301Biological

    Brachyury yeast vaccine

  • haNKBiological

    NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous [IV] Infusion (haNK™ for Infusion)

Study groups in NCT03197571
Study groupRoleWhat they receive
Nant Urothelial Cancer VaccineExperimentalavelumab, bevacizumab, capecitabine, cisplatin, cyclophosphamide, 5-fluorouracil, fulvestrant, leucovorin, nab-paclitaxel, lovaza, stereotactic body radiation therapy, ALT-803, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, and haNK.
Receives: Biological: avelumab; Biological: bevacizumab; Drug: capecitabine; Drug: cisplatin; Drug: cyclophosphamide; Drug: 5Fluorouracil (5-FU); Drug: fulvestrant; Drug: leucovorin; Drug: nab-paclitaxel; Drug: Lovaza; Radiation: Stereotactic Body Radiation Therapy; Biological: ALT-803; Biological: ETBX-011; Biological: ETBX-021; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-4000; Biological: GI-6207; Biological: GI-6301; Biological: haNK

What is being measured

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

  1. Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

    Phase 1b primary endpoint (safety)

    Measured: 1 year

  2. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Phase 2 primary endpoint (ORR by RECIST)

    Measured: 1 year

  3. ORR by Immune-related response criteria (irRC)

    Phase 2 primary endpoint (ORR by irRC)

    Measured: 1 year

Secondary outcomes (9)

  1. ORR by RECIST Version 1.1

    Phase 1b secondary endpoint (ORR by RECIST)

    Measured: 1 year

  2. ORR by irRC

    Phase 1b secondary endpoint (ORR by irRC)

    Measured: 1 year

  3. Progression-free survival (PFS) by RECIST Version 1.1

    Phase 1b and 2 secondary endpoint (PFS by RECIST)

    Measured: 2 years

  4. PFS by irRC

    Phase 1b and 2 secondary endpoint (PFS by irRC)

    Measured: 2 years

  5. Overall survival (OS): time from the date of first treatment to the date of death (any cause)

    Phase 1b and 2 secondary endpoint (OS)

    Measured: 2 years

  6. Duration of response (DR): time from the date of first response (partial response (PR) or complete response (CR)) to the date of disease progression or death (any cause) whichever occurs first

    Phase 1b and 2 secondary endpoint (DR)

    Measured: 2 years

  7. Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months

    Phase 1b and 2 secondary endpoint (DCR)

    Measured: 2 months

  8. Patient-reported outcomes (PRO) using the using the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) instrument

    Phase 1b and 2 secondary endpoint (PRO)

    Measured: 2 years

  9. Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03

    Phase 2 secondary endpoint (AEs)

    Measured: 1 year

Timeline

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

  1. First posted23 Jun 2017
  2. Study startDec 2017 (estimated)
  3. Primary completionJan 2019 (estimated)
  4. Study completion28 Dec 2021

Why it stopped: Trial 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03197571
Sponsor's protocol ID
QUILT-3.048
Status last verified
Oct 2017
First submitted
20 Jun 2017
Last updated
21 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing avelumab, bevacizumab and capecitabine in people with Urothelial Carcinoma, run by ImmunityBio, Inc..

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 9 inclusion and 29 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 21 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

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 adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. (time frame: 1 year). The study lists 3 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 NCT03197571.

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 21 Feb 2025.

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