QUILT 3.071: NANT Colorectal Cancer (CRC) Vaccine

Phase 1

Terminated

• Conditions: mCRC; Colorectal Cancer Metastatic
• Interventions: 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

• Registration Number: NCT03563157
• Lead Sponsor: ImmunityBio, Inc.

Brief 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.

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 Timeline

• Study First Submitted: 2018-05-22
• Study First Submitted QC: 2018-06-15
• Study First Posted: 2018-06-20
• Study Start: 2018-09-28
• Primary Completion: 2019-04-21
• Study Completion: 2019-08-21
• Results First Submitted: 2024-04-04
• Status Verified: 2024-12
• Results First Submitted QC: 2024-12-09
• Last Update Submitted: 2024-12-09
• Results First Posted: 2024-12-11
• Last Update Posted: 2024-12-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

1. Age ≥ 18 years.

2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.

3. 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.

4. ECOG performance status of 0 or 1.

5. Have at least 1 measurable lesion of ≥ 1.0 cm.

6. 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.

7. Must be willing to provide blood samples prior to the start of treatment on this study for prospective 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, IUDs, and abstinence.

    Phase 2 single-arm component only

11. 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

1. MSI-high or MMR-deficient tumors eligible for, but not yet treated with, a PD-1 inhibitor.

2. 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.

3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma).

4. History of organ transplant requiring immunosuppression.

5. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

6. Inadequate organ function, evidenced by the following laboratory results:

   1. ANC < 1,000 cells/mm^3.
   2. Uncorrectable grade 3 anemia (hemoglobin < 8 g/dL)
   3. Platelet count < 75,000 cells/mm^3.
   4. Total bilirubin > ULN (unless the subject has documented Gilbert's syndrome).
   5. AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
   6. ALP > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
   7. Serum creatinine > 2.0 mg/dL or 177 μmol/L.
   8. Serum anion gap > 16 mEq/L or arterial blood with pH < 7.3.

7. 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.

8. Serious myocardial dysfunction defined by ECHO as absolute LVEF 10% below the institution's lower limit of predicted normal.

9. Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.

10. Positive results of screening test for HIV.

11. 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.

12. Known hypersensitivity to any component of the study medication(s).

13. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug reaction with any of the study medications.

14. 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.

15. Concurrent or prior use of a strong CYP2C8 inhibitor (gemfibrozil) or moderate CYP2C8 inducer (rifampin) within 14 days before study day 1.

16. 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.

17. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

18. Concurrent participation in any interventional clinical trial.

19. Pregnant and nursing women.

    Phase 2 randomized component only

20. Prior regorafenib treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NANT Colorectal Cancer (CRC) Vaccine	Nab-paclitaxel	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.
NANT Colorectal Cancer (CRC) Vaccine	Aldoxorubicin Hydrochloride	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.
NANT Colorectal Cancer (CRC) Vaccine	ALT-803	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.
NANT Colorectal Cancer (CRC) Vaccine	ETBX-011	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.
NANT Colorectal Cancer (CRC) Vaccine	ETBX-061	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.
NANT Colorectal Cancer (CRC) Vaccine	GI-4000	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.
NANT Colorectal Cancer (CRC) Vaccine	GI-6207	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.
NANT Colorectal Cancer (CRC) Vaccine	Capecitabine	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.
NANT Colorectal Cancer (CRC) Vaccine	haNK	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.
NANT Colorectal Cancer (CRC) Vaccine	Avelumab	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.
NANT Colorectal Cancer (CRC) Vaccine	Cyclophosphamide	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.
NANT Colorectal Cancer (CRC) Vaccine	5-Fluorouracil	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.
NANT Colorectal Cancer (CRC) Vaccine	Cetuximab	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.
NANT Colorectal Cancer (CRC) Vaccine	Leucovorin	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.
NANT Colorectal Cancer (CRC) Vaccine	Oxaliplatin	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.
NANT Colorectal Cancer (CRC) Vaccine	Regorafenib	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.
NANT Colorectal Cancer (CRC) Vaccine	SBRT	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.
Regorafenib	Regorafenib	Regorafenib will be administered to subjects in this study.
NANT Colorectal Cancer (CRC) Vaccine	ETBX-021	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.
NANT Colorectal Cancer (CRC) Vaccine	ETBX-051	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.
NANT Colorectal Cancer (CRC) Vaccine	GI-6301	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)	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.	Graded Using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03

Secondary Outcome Measures

Name	Time	Method
Quality of Life by Patient Reported Outcomes (PRO)	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.	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.
Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by 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 until confirmed disease progression, up to 4 months	Disease control is defined as subjects with a confirmed CR, PR, or SD lasting for at least 2 months.
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 until disease progression, up to 4 months	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.
Progression Free Survival by RECIST Version 1.1 and irRC	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.	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.
Duration of Response (DOR) 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 until confirmed disease progression, up to 4 months	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.
Overall Survival	Participants were assessed from screening to death.	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.
Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by RECIST Version 1.1.	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	Disease control is defined as subjects with a confirmed CR, PR, or SD lasting for at least 2 months.

Trial Locations

Locations (1)

Chan Soon-Shiong Institute for Medicine; 🇺🇸 El Segundo, California, United States