QUILT-3.090: NANT Squamous Cell Carcinoma (SCC) Vaccine: Subjects With SCC Who Have Progressed

Phase 1

Terminated

• Conditions: Squamous Cell Carcinoma
• Interventions: Drug: Aldoxorubicin HCl; Biological: ETBX-011; Biological: ETBX-021; Biological: ETBX-051; Biological: ETBX-061; Biological: GI-4000; Biological: GI-6207; Biological: GI-6301; Biological: haNK for infusion; Drug: Avelumab; Drug: bevacizumab; Drug: Capecitabine; Drug: Cetuximab; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Fluorouracil; Drug: Leucovorin; Drug: nab-Paclitaxel; Drug: Necitumumab; Procedure: SBRT; Biological: N-803

• Registration Number: NCT03387111
• Lead Sponsor: ImmunityBio, Inc.

Brief Summary

This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with SCC who have progressed on or after previous platinum-based chemotherapy and anti-PD-1/PD-L1 therapy. Phase 2 will be based on Simon's two-stage optimal design.

Detailed Description

Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects who experience ongoing stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at the Investigator's and Sponsor's discretion. Subjects may remain in the maintenance phase of the study for up to 1 year. The duration of the maintenance phase can exceed 1 year if the subject continues to benefit, per the Investigator's and Sponsor's discretion. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. The time on study treatment, including both the induction and maintenance phases, is up to 2 years. The duration of the study may exceed 2 years if the subject remains in the maintenance phase for more than 1 year, as described above.

Study Timeline

• Study First Submitted: 2017-12-21
• Study First Submitted QC: 2017-12-28
• Study First Posted: 2017-12-29
• Study Start: 2018-01-09
• Primary Completion: 2019-04-17
• Status Verified: 2020-08
• Study Completion: 2021-01-11
• Results First Submitted: 2024-04-03
• Results First Submitted QC: 2024-07-23
• Last Update Submitted: 2024-07-23
• Results First Posted: 2024-08-05
• Last Update Posted: 2024-08-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

1. Age ≥ 18 years.
2. Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
3. Histologically-confirmed HNSCC or squamous NSCLC with progression on or after platinum-based chemotherapy and anti-PD-1/PD-L1 therapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Have at least 1 measurable lesion of ≥ 1.0 cm.
6. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen following the conclusion of the most recent anticancer treatment. 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.
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of treatment, 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, intrauterine devices (IUDs), and abstinence.

Exclusion Criteria

1. 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.

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

3. History of organ transplant requiring immunosuppression.

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

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

   1. Absolute neutrophil count < 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 greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
   5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
   6. Alkaline phosphatase levels > 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.

6. 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.

7. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) 10% below the institution's lower limit of predicted normal.

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

9. Positive results of screening test for human immunodeficiency virus (HIV).

10. 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.

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

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

13. 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.

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

15. 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.

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

17. Concurrent participation in any interventional clinical trial.

18. Pregnant and nursing women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NANT Squamous Cell Carcinoma (SCC) Vaccine	ETBX-011	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Aldoxorubicin HCl	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	GI-6207	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	haNK for infusion	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	ETBX-051	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	ETBX-021	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	ETBX-061	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	GI-4000	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	GI-6301	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	N-803	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	nab-Paclitaxel	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	SBRT	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Necitumumab	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Cyclophosphamide	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	bevacizumab	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Cetuximab	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Avelumab	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Capecitabine	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Cisplatin	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Fluorouracil	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, SBRT.
NANT Squamous Cell Carcinoma (SCC) Vaccine	Leucovorin	Combination of agents were administered in this study: Aldoxorubicin HCl, ETBX-011, ETBX-021, ETBX-051, ETBX-061, GI-4000, GI-6207, GI-6301, haNK, N-803, avelumab, bevacizumab, capecitabine, cetuximab, cisplatin, cyclophosphamide, fluorouracil, leucovorin, nab-paclitaxel, necitumumab, 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 15.5 months	Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate 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 11 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 immune-related response criteria (irRC).; 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.	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 11 months.	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions 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.
Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by RECIST Version 1.1	Up to 11 months	Disease control is defined as subjects with a confirmed CR, PR, or SD lasting for at least 2 months
Quality of Life (QoL) by Patient Reported Outcomes	Up to 15.5 months	QoL was conducted via PROs using the Functional Assessment of Cancer Therapy - Head and Neck (FACT-H\&N) or Functional Assessment of Cancer Therapy - Lung (FACT-L) questionnaire. The FACT-H\&N and FACT-L compilation of general questions divided into five QoL subscales: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, and Additional Concerns.; It uses 5-point Likert-type response categories ranging from 0 = 'not at all' to 4 = 'very much'. Each subscale consists of 6-12 questions to answer.
Disease Control Rate (Confirmed Complete Response, Partial Response, or Stable Disease Lasting for at Least 2 Months) by irRC	Up to 11 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	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 11 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 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 11 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.
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.
Duration of Response (DOR) 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 11 months.	DOR was defined as the time from the date of first response (PR or CR) to the date of disease progression or death (any cause) whichever occurred first. Responding subjects completed study follow-up or initiated a new anticancer therapy prior to documented PD was censored in the DOR analysis at the last known date the subject was progression free prior completing follow-up or initiating the new therapy.

Trial Locations

Locations (1)

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