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

NCT03647423 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: QUILT-3.091
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chordoma; Unresectable Malignant Neoplasm

Outcome Measures

Primary Outcomes (2)

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

  Phase 1b primary endpoint

  9 weeks

• Progression-free survival (PFS) by RECIST v1.1

  Phase 2 primary endpoint

  1 years

Secondary Outcomes (16)

• Objective response rate by RECIST v1.1

  9 weeks

• Objective response rate by irRC

  9 weeks

• Progression-free survival (PFS) by RECIST v1.1

  9 weeks

• Progression-free survival (PFS) by irRC

  9 weeks

• Overall survival

  9 weeks

Study Arms (2)

NANT Chordoma Vaccine

EXPERIMENTAL

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.

Biological: Aldoxorubicin Hydrochloride; Biological: ALT-803; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-6301; Biological: haNK; Drug: Avelumab; Drug: Cetuximab; Drug: Cyclophosphamide

Controlled Arm - Radiation

ACTIVE COMPARATOR

SBRT

Radiation: SBRT

Interventions

Aldoxorubicin Hydrochloride BIOLOGICAL

Aldoxorubicin Hydrochloride HCI

NANT Chordoma Vaccine

ALT-803 BIOLOGICAL

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

NANT Chordoma Vaccine

ETBX-051 BIOLOGICAL

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

NANT Chordoma Vaccine

ETBX-061 BIOLOGICAL

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

NANT Chordoma Vaccine

GI-6301 BIOLOGICAL

Brachyury yeast

NANT Chordoma Vaccine

haNK BIOLOGICAL

haNK™, NK-92 \[CD16.158V, ER IL-2\]

NANT Chordoma Vaccine

Avelumab DRUG

injection

Also known as: BAVENCIO®

NANT Chordoma Vaccine

Cetuximab DRUG

Injection

Also known as: ERBITUX®

NANT Chordoma Vaccine

Cyclophosphamide DRUG

Capsules

Also known as: Cytoxan

NANT Chordoma Vaccine

SBRT RADIATION

Stereotactic body radiation therapy

Controlled Arm - Radiation

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 recurrent or unresectable chordoma that would require radiation as a primary means for treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have at least 1 measurable lesion of ≥ 1.0 cm.
• 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 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.
• 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.

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: 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.
• 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.
• Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) 10% below the institution's lower limit of predicted normal.
• 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).
• 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 30 days prior to screening for this study, except for testosterone- lowering therapy in men with prostate cancer.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (1)

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

Location

MeSH Terms

Conditions

Chordoma

Interventions

ALT-803; avelumab; Cetuximab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

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

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

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 27, 2018
• Study Start: August 31, 2018
• Primary Completion: August 31, 2020
• Study Completion: December 28, 2021
• Last Updated: February 21, 2025

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)