QUILT-3.091 NANT Chordoma Vaccine vs Radiation in Subjects With Unresectable Chordoma.

NCT ID: NCT03647423

Last Updated: 2025-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-31

Study Completion Date

2021-12-28

Brief Summary

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QUILT 3.091 Chordoma Vaccine: Phase 1B/2 NANT Chordoma Vaccine vs Radiation in Subjects with Unresectable Chordoma.

Detailed Description

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The NANT Chordoma Vaccine regimen will be administered in 2 phases, an induction and a maintenance phase.

Subjects will continue induction treatment for up to 1 year. Those who have a confirmed complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects who experience ongoing stable disease (SD) or an ongoing partial response (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.

In the randomized component of the phase 2 portion of the study, the control arm will be treated with radiation according to established SoC protocols as determined by the Investigator.

In the phase 2 single-arm component of the study, subjects will be enrolled in the first stage of Simon's two-stage optimal design. If the study proceeds to the second stage of Simon's two-stage optimal design, additional subjects will be enrolled in the second stage.

Conditions

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Chordoma Unresectable Malignant Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Chordoma Vaccine: A randomized phase 1b/2 trial of the NANT chordoma vaccine vs. radiation in subjects with unresectable chordoma.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NANT Chordoma Vaccine

A combination of agents will be administered to subjects in this study: Aldoxorubicin Hydrochloride HCI, ALT-803, ETBX-051, ETBX-061, GI-6301, haNK, avelumab, cetuximab, cyclophosphamide, SBRT.

Group Type EXPERIMENTAL

Aldoxorubicin Hydrochloride

Intervention Type BIOLOGICAL

Aldoxorubicin Hydrochloride HCI

ALT-803

Intervention Type BIOLOGICAL

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

ETBX-051

Intervention Type BIOLOGICAL

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

ETBX-061

Intervention Type BIOLOGICAL

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

GI-6301

Intervention Type BIOLOGICAL

Brachyury yeast

haNK

Intervention Type BIOLOGICAL

haNK™, NK-92 \[CD16.158V, ER IL-2\]

Avelumab

Intervention Type DRUG

injection

Cetuximab

Intervention Type DRUG

Injection

Cyclophosphamide

Intervention Type DRUG

Capsules

Controlled Arm - Radiation

SBRT

Group Type ACTIVE_COMPARATOR

SBRT

Intervention Type RADIATION

Stereotactic body radiation therapy

Interventions

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Aldoxorubicin Hydrochloride

Aldoxorubicin Hydrochloride HCI

Intervention Type BIOLOGICAL

ALT-803

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

Intervention Type BIOLOGICAL

ETBX-051

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

Intervention Type BIOLOGICAL

ETBX-061

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

Intervention Type BIOLOGICAL

GI-6301

Brachyury yeast

Intervention Type BIOLOGICAL

haNK

haNK™, NK-92 \[CD16.158V, ER IL-2\]

Intervention Type BIOLOGICAL

Avelumab

injection

Intervention Type DRUG

Cetuximab

Injection

Intervention Type DRUG

Cyclophosphamide

Capsules

Intervention Type DRUG

SBRT

Stereotactic body radiation therapy

Intervention Type RADIATION

Other Intervention Names

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BAVENCIO® ERBITUX® Cytoxan

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years.
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
3. Histologically-confirmed recurrent or unresectable chordoma that would require radiation as a primary means for treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Have at least 1 measurable lesion of ≥ 1.0 cm.
6. 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.
7. Must be willing to provide blood samples prior to the start of treatment on this study for tumor molecular profiling and exploratory analyses.
8. 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.
9. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
10. 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.

Randomized component only - 11. Must be able to be classified into at least 1 of the below 3 categories: i. Recurred within 6 months after treatment, ii. Have metastatic disease, iii. Meet ≥ 4 of the histopathologic and immunohistochemical criteria: • Poorly differentiated histopathologic sub type, • Mitotic figures ≥ 3, • Apoptosis present. • Prominent nucleoli present, • Necrosis present, • Ki67 ≥ 6%, • p53 ≥ 25%

Single-arm component only 12. Must have progressed on or after radiation monotherapy in the randomized portion of the study OR been ineligible for the randomized portion but had progressed or experienced unacceptable toxicity on SoC prior to enrollment on the study.

Exclusion Criteria

1. 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.
2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis,Addison's disease, or autoimmune disease associated with lymphoma).
3. History of organ transplant requiring immunosuppression.
4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
5. Inadequate organ function, evidenced by the following laboratory results: a. Absolute neutrophil count \< 1,000 cells/mm\^3, b. Uncorrectable grade 3 anemia (hemoglobin \< 8 g/dL), c. Platelet count \< 75,000 cells/mm\^3, d. Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome), e. Aspartate aminotransferase (AST \[SGOT\]) or alanine aminotransferase (ALT \[SGPT\]) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases), f. Alkaline phosphatase levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases), g. Serum creatinine \> 2.0 mg/dL or 177 μmol/L, h. Serum anion gap \> 16 mEq/L or arterial blood with pH \< 7.3.
6. 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. Subjects with uncontrolled hypertension should be medically managed on a stable regimen to control hypertension prior to study entry.
7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) 10% below the institution's lower limit of predicted normal.
8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
9. Positive results of screening test for human immunodeficiency virus (HIV).
10. 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.
11. Known hypersensitivity to any component of the study medication(s).
12. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.
13. 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.
14. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.
15. Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to screening for this study, except for testosterone- lowering therapy in men with prostate cancer.
16. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
17. Concurrent participation in any interventional clinical trial.
18. Pregnant and nursing women.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ImmunityBio, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Chan Soon-Shiong Institute for Medicine

El Segundo, California, United States

Site Status

Countries

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United States

Other Identifiers

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QUILT-3.091

Identifier Type: -

Identifier Source: org_study_id

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