Colorectal Cancer MetastaticPhase 1/2NCT03563157
QUILT 3.071: NANT Colorectal Cancer (CRC) Vaccine
A Phase 1/2 study testing Aldoxorubicin Hydrochloride, ALT-803 and ETBX-011 in people with Colorectal Cancer Metastatic and mCRC, run by ImmunityBio, Inc. at 1 site in United States.
Trial summary
QUILT 3.071 NANT Colorectal Cancer (CRC) Vaccine: This is a Phase 1b/2 study investigating the effect of NANT CRC vaccine vs regorafenib in subjects with CRC who were previously treated with SOC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic, mCRC
- What is being tested?
- Aldoxorubicin Hydrochloride, ALT-803 and ETBX-011
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Sep 2018to 21 Aug 2019
- Phase
- Phase 1/2
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 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.
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- 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.
Who cannot join
- 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:
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- 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.
- Phase 2 randomized component only
- Prior regorafenib treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Chan Soon-Shiong Institute for Medicine
El Segundo, California, 90245
About this study
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
QUILT 3.071 NANT Colorectal Cancer (CRC) Vaccine: This is a Phase 1b/2 study investigating the effect of NANT CRC vaccine vs regorafenib in subjects with CRC who were previously treated with SOC.
Read the 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
- Conditions
- Colorectal Cancer Metastatic, mCRC
- Being tested
- Aldoxorubicin Hydrochloride, ALT-803, ETBX-011, ETBX-021, ETBX-051
- Keywords
- Colorectal Cancer, Metastatic Colorectal Cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aldoxorubicin HydrochlorideBiological
Aldoxorubicin Hydrochloride HCI
ALT-803Biological
Recombinant human super agonist interleukin-15 (IL-15) complex [also known as IL-15N72D;IL-15RaSu/IgG1 Fe complex1]
ETBX-011Biological
Ad5 [E1-, E2b-]-CEA
ETBX-021Biological
Ad5 [E1-, E2b-]-[HER2]
ETBX-051Biological
Ad5 [E1-, E2b-]-Brachyury
ETBX-061Biological
Ad5 [E1-, E2b-]-mucin 1 [MUC1]
GI-4000Biological
RAS yeast
GI-6207Biological
CEA yeast
GI-6301Biological
Brachyury yeast
haNKBiological
haNK™, NK-92 [CD16.158V, ER IL-2]
AvelumabDrug
BAVENCIO® injection
CapecitabineDrug
XELODA® tablets
CetuximabDrug
ERBITUX® injection
CyclophosphamideDrug
Cyclophosphamide Capsules
5-FluorouracilDrug
5-FU; Fluorouracil Injection
LeucovorinDrug
Leucovorin Calcium
Nab-paclitaxelDrug
ABRAXANE® for Injectable Suspension [paclitaxel protein-bound particles for injectable suspension] [albumin-bound]
OxaliplatinDrug
ELOXATIN® injection
RegorafenibDrug
STIVARGA® tablets
SBRTProcedure or surgery
Stereotactic body radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| NANT Colorectal Cancer (CRC) Vaccine | Experimental | 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. Receives: 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 |
| Regorafenib | Active comparator | Regorafenib will be administered to subjects in this study. Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With 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
Measured: 30 days after last dose, up to 6 months or until they experience confirmed progressive disease or unacceptable toxicity, withdrawn consent, or if the Investigator feels it is no longer in their best interest.
Secondary outcomes (7)
Objective Response Rate by RECIST Version 1.1 and irRC
Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in accordance with RECIST Version 1.1.
An objective response is defined as a confirmed complete or partial overall response with confirmation occurring at least 4 weeks after the initial response is observed.
Measured: Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression, up to 4 months
Progression Free Survival by RECIST Version 1.1 and irRC
PFS was evaluated using Kaplan-Meier methods. PFS was defined as the time from the date of first treatment to the date of disease progression or death (any cause) whichever occurs first. Subjects completing study follow-up or initiating a new anticancer therapy prior to documented PD was censored in the PFS analysis at the last known date the subject was progression free prior to completing follow-up or initiating the new therapy.
Measured: Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first, up to 9 months.
Duration of Response (DOR) by RECIST Version 1.1 and irRC
DOR was be defined as the time from the date of first response (PR or CR) to the date of disease progression or death (any cause) whichever occurs first. Responding subjects completed study follow-up or initiating a new anticancer therapy prior to documented PD were censored in the DOR analysis at the last known date the subject was progression free prior completing follow-up or initiating the new therapy.
Measured: Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression, up to 4 months
Overall Survival
OS was evaluated using Kaplan-Meier methods. OS was defined as the time from the date of first treatment to the date of death (any cause). Participants who were alive at the end of follow-up were censored in the OS analysis at the last known date alive.
Measured: Participants were assessed from screening to death.
Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by RECIST Version 1.1.
Disease control is defined as subjects with a confirmed CR, PR, or SD lasting for at least 2 months.
Measured: Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression, up to 4 months
Quality of Life by Patient Reported Outcomes (PRO)
PROs were assessed using the Functional Assessment of Cancer Therapy-colorectal cancer (FACT-C) questionnaire. The FACT-Hep is compilation of general questions divided into five QOL subscales:
Physical Well-Being - Scores ranging from 0-28 Social/Family Well-Being - Scores ranging from 0-28 Emotional Well-Being - Scores ranging from 0-24 Functional Well-Being - Scores ranging from 0-28 Additional Concerns - Scores ranging from 0-36 It uses 5-point Likert-type response categories ranging from 0 = 'not at all' to 4 = 'very much' The higher scales and subscales indicate better quality of life. Negatively worded items were reverse scored. If the missing for each subscale was less than 50%, the prorating scores were computed for the subscale.
Measured: Assessments occurred at Baseline, Cycle 2 Day 8 (C2D8), Cycle 5 Day 1 (C5D1), at an unscheduled visit prior to end of treatment, and at end of treatment (up to 5 months). Each cycle was 28 days.
Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by irRC
Disease control is defined as subjects with a confirmed CR, PR, or SD lasting for at least 2 months.
Measured: Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression, up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2018
- Study start28 Sep 2018
- Primary completion21 Apr 2019
- Study completion21 Aug 2019
Why it stopped: low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- ImmunityBio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03563157
- Sponsor's protocol ID
- QUILT-3.071
- Status last verified
- Dec 2024
- First submitted
- 22 May 2018
- Last updated
- 11 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No