QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer

Sponsor

ImmunityBio, Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT03574649

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized phase 2 study to compare the efficacy of neoadjuvant, consolidation, and adjuvant immunotherapy (NANT NSCLC Combination Immunotherapy; experimental arm) to standard of care (surgery and adjuvant chemotherapy; control arm) in subjects with stage II-IIIa resectable NSCLC.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Nab-paclitaxel Drug: Cisplatin Drug: 5Fluorouracil Drug: Cyclophosphamide Biological: ETBX-011 Biological: ETBX-051 Biological: ETBX-061 Biological: GI-4000 Biological: GI-6301 Drug: Aldoxorubicin Drug: Avelumab Drug: ALT-803 Biological: haNK Drug: Docetaxel Drug: carboplatin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer

Anticipated Study Start Date :

Sep 1, 2018

Anticipated Primary Completion Date :

Dec 30, 2019

Anticipated Study Completion Date :

Dec 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NANT NSCLC Combination Immunotherapy regimen	Drug: Nab-paclitaxel 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 Drug: Cisplatin (SP-4-2)-diamminedichloroplatinum(II) Drug: 5Fluorouracil 5-fluoro-2,4 (1H,3H)-pyrimidinedione Drug: Cyclophosphamide 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate Biological: ETBX-011 adenovirus serotype-5 [Ad5] [E1-, E2b-]-carcinoembryonic antigen [CEA] vaccine Biological: ETBX-051 Ad5 [E1-, E2b-]-Brachyury vaccine Biological: ETBX-061 Ad5 [E1-, E2b-]-mucin 1 [MUC1] vaccine Biological: GI-4000 RAS yeast vaccine Biological: GI-6301 Brachyury yeast vaccine Drug: Aldoxorubicin INNO-206 Drug: Avelumab Fully human anti-PD-L1 IgG1 lambda monoclonal antibody Drug: ALT-803 recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL-15N72D:IL-15RαSu/IgG1 Fc complex] Biological: haNK NK-92 [CD16.158V, ER IL-2], Suspension for Intravenous [IV] Infusion (haNK™ for Infusion)
Active Comparator: Standard of Care	Drug: Nab-paclitaxel 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 Drug: Cisplatin (SP-4-2)-diamminedichloroplatinum(II) Drug: Docetaxel Docetaxel Drug: carboplatin carboplatin

Arm

Intervention/Treatment

Experimental: NANT NSCLC Combination Immunotherapy regimen

Drug: Nab-paclitaxel

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

Drug: Cisplatin

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

Drug: 5Fluorouracil

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

Drug: Cyclophosphamide

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

Biological: ETBX-011

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

Biological: ETBX-051

Ad5 [E1-, E2b-]-Brachyury vaccine

Biological: ETBX-061

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

Biological: GI-4000

RAS yeast vaccine

Biological: GI-6301

Brachyury yeast vaccine

Drug: Aldoxorubicin

INNO-206

Drug: Avelumab

Fully human anti-PD-L1 IgG1 lambda monoclonal antibody

Drug: ALT-803

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

Biological: haNK

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

Active Comparator: Standard of Care

Drug: Nab-paclitaxel

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

Drug: Cisplatin

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

Drug: Docetaxel

Docetaxel

Drug: carboplatin

carboplatin

Outcome Measures

Primary Outcome Measures

Relapse-free survival ( RFS) [18 months]
time from the date of randomization to the date of first radiographically determined new lesion by RECIST Version 1.1 based on BICR or date of death (by any cause), whichever occurs first

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years.
Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
Histologically-confirmed stage II-IIIa NSCLC.
ECOG performance status of 0 to 2.
Have at least 1 measurable lesion of > 1.0 cm.
Must have a recent 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.
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.

Exclusion Criteria:

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/mm3.
Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL).
Platelet count < 75,000 cells/mm3.
Total bilirubin greater than the ULN; unless the subject has documented Gilbert's syndrome).
AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
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.
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 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 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.
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.