QUILT 3.071: NANT Colorectal Cancer (CRC) Vaccine

Sponsor

ImmunityBio, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03563157

Collaborator

(none)

332

Enrollment

Location

Arms

55.2

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

QUILT 3.071 NANT Colorectal Cancer (CRC) Vaccine: Phase 1b/2 NANT CRC Vaccine vs Regorafenib in Subjects with CRC Who have Previously Treated with SOC.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic mCRC	Biological: Aldoxorubicin Hydrochloride 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 Drug: Avelumab Drug: Capecitabine Drug: Cetuximab Drug: Cyclophosphamide Drug: 5-Fluorouracil Drug: Leucovorin Drug: Nab-paclitaxel Drug: Oxaliplatin Drug: Regorafenib Procedure: SBRT	Phase 1/Phase 2

Detailed Description

NANT Colorectal Cancer (CRC) Vaccine: A phase 1b/2 Trial of the NANT CRC Vaccine vs Regorafenib in Subjects with Metastatic CRC Who Have Been Previously Treated with Standard-Of-Care Therapy

Study Design

Study Type:

Interventional

Anticipated Enrollment :

332 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

NANT Colorectal Cancer (CRC) Vaccine: A Phase 1b/2 Trial of the NANT CRC Vaccine vs Regorafenib in Subjects With Metastatic CRC Who Have Been Previously Treated With Standard-of-Care Therapy

Actual Study Start Date :

May 25, 2018

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NANT Colorectal Cancer (CRC) Vaccine A combination of agents will be administered to subjects in this study: Aldoxorubicin HCI, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, Avelumab, Capecitabine, Cetuximab, Cyclophosphamide, 5-Fluorouracil, Leucovorin, Nab-paclitaxel, Oxaliplatin, Regorafenib, SBRT.	Biological: Aldoxorubicin Hydrochloride Aldoxorubicin Hydrochloride HCI Biological: ALT-803 Recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL-15N72D;IL-15RaSu/IgG1 Fe complex1] Biological: ETBX-011 Ad5 [E1-, E2b-]-CEA Biological: ETBX-021 Ad5 [E1-, E2b-]-[HER2] Biological: ETBX-051 Ad5 [E1-, E2b-]-Brachyury Biological: ETBX-061 Ad5 [E1-, E2b-]-mucin 1 [MUC1] Biological: GI-4000 RAS yeast Biological: GI-6207 CEA yeast Biological: GI-6301 Brachyury yeast Biological: haNK haNK™, NK-92 [CD16.158V, ER IL-2] Drug: Avelumab BAVENCIO® injection Drug: Capecitabine XELODA® tablets Drug: Cetuximab ERBITUX® injection Drug: Cyclophosphamide Cyclophosphamide Capsules Drug: 5-Fluorouracil 5-FU; Fluorouracil Injection Drug: Leucovorin Leucovorin Calcium Drug: Nab-paclitaxel ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles for injectable suspension] [albumin-bound] Drug: Oxaliplatin ELOXATIN® injection Drug: Regorafenib STIVARGA® tablets Procedure: SBRT Stereotactic body radiation therapy
Active Comparator: Regorafenib In subjects with metastatic CRC who have been previously treated with standard-of-care (SOC) therapy.	Drug: Regorafenib STIVARGA® tablets

Arm

Intervention/Treatment

Experimental: NANT Colorectal Cancer (CRC) Vaccine

A combination of agents will be administered to subjects in this study: Aldoxorubicin HCI, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, Avelumab, Capecitabine, Cetuximab, Cyclophosphamide, 5-Fluorouracil, Leucovorin, Nab-paclitaxel, Oxaliplatin, Regorafenib, SBRT.

Biological: Aldoxorubicin Hydrochloride

Aldoxorubicin Hydrochloride HCI

Biological: ALT-803

Recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL-15N72D;IL-15RaSu/IgG1 Fe complex1]

Biological: ETBX-011

Ad5 [E1-, E2b-]-CEA

Biological: ETBX-021

Ad5 [E1-, E2b-]-[HER2]

Biological: ETBX-051

Ad5 [E1-, E2b-]-Brachyury

Biological: ETBX-061

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

Biological: GI-4000

RAS yeast

Biological: GI-6207

CEA yeast

Biological: GI-6301

Brachyury yeast

Biological: haNK

haNK™, NK-92 [CD16.158V, ER IL-2]

Drug: Avelumab

BAVENCIO® injection

Drug: Capecitabine

XELODA® tablets

Drug: Cetuximab

ERBITUX® injection

Drug: Cyclophosphamide

Cyclophosphamide Capsules

Drug: 5-Fluorouracil

5-FU; Fluorouracil Injection

Drug: Leucovorin

Leucovorin Calcium

Drug: Nab-paclitaxel

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

Drug: Oxaliplatin

ELOXATIN® injection

Drug: Regorafenib

STIVARGA® tablets

Procedure: SBRT

Stereotactic body radiation therapy

Active Comparator: Regorafenib

In subjects with metastatic CRC who have been previously treated with standard-of-care (SOC) therapy.

Drug: Regorafenib

STIVARGA® tablets

Outcome Measures

Primary Outcome Measures

Incidence of treatment-emergent AEs and SAEs, graded using the NCI CTCAE Version 4.03 [2 years]
Phase 1b
Progression Free Survival from baseline to progression, per RECIST 1.1 [2 years]
Phase 2 Randomized Component
Overall Response Rate, as determined by the percentage of patients achieving Partial or Complete Response per RECIST 1.1 [1 year]
Phase 2 Single Arm Component

Secondary Outcome Measures

ORR for Phase 1b and Phase 2 Randomized Component [1 year]
Overall Response Rate, as determined by the percentage of patients achieving Partial or Complete response per RECIST 1.1 and irRC
PFS for Phase 1b and Phase 2 Single Arm Component [2 years]
Progression Free Survival from baseline to progression per RECIST 1.1 and irRC
OS for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component [2 years]
Overall Survival from first treatment to date of death (any cause)
DOR for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component [2 years]
Duration of Response from date of first response to date of disease progression or death (any cause), per RECIST 1.1 and irRC
DCR for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component [1 year]
Disease Control Rate: the number of patients with a CR, PR or SD lasting at least 2 months per RECIST 1.1 and irRC
QoL for Phase 1b, Phase 2 Randomized, and Phase 2 Single Arm Component [2 years]
Quality of Life as assessed by Patient Reported Outcomes using the FACT-C questionnaire

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 recurrent or metastatic CRC previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy; or subjects who are ineligible for these therapies.
ECOG performance status of 0 or 1.
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.
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, IUDs, and abstinence.

Phase 2 single-arm component only

Must have progressed on or after regorafenib treatment in the randomized phase 2 portion of the study OR progressed or experienced unacceptable toxicity on SoC and regorafenib prior to enrollment on the study.

Exclusion Criteria:

MSI-high or MMR-deficient tumors eligible for, but not yet treated with, a PD-1 inhibitor.
Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drugs 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:
ANC < 1,000 cells/mm^3.
Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL)
Platelet count < 75,000 cells/mm^3.
Total bilirubin > 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 > 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 CYP3A4 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.