QUILT 2.023: A Study of N-803 in Combination With Current Standard of Care vs Standard of Care as First-Line Treatment for Patients With Stage 3 or 4 NSCLC.

Sponsor

ImmunityBio, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03520686

Collaborator

(none)

1,538

Enrollment

Locations

Arms

73.5

Anticipated Duration (Months)

46.6

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 3, open-label, 3-cohort, randomized study to compare the safety and efficacy of N-803 in combination with the current standard of care (experimental arms) versus standard of care alone (control arms), as first-line treatment for subjects with stage 3 or 4 advanced or metastatic NSCLC. Treatment will continue for up to 2 years, or until the patient experiences confirmed progressive disease or unacceptable toxicity, withdraws consent, or if the investigator feels that it is no longer in the patient's best interest to continue treatment. Patients will be followed for disease progression, post-therapies, and survival through 24 months after the first dose of study drug.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: N-803 + Pembrolizumab Drug: N-803 + Carboplatin + Nab-paclitaxel + Pembrolizumab Drug: N-803 + Cisplatin or Carboplatin + Pembrolizumab + Pemetrexed Drug: Pembrolizumab Drug: Carboplatin + Nab-paclitaxel or Paclitaxel + Pembrolizumab Drug: Cisplatin or Carboplatin + Pembrolizumab + Pemetrexed	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1538 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

QUILT 2.023: A Phase 3, Open-Label, 3-Cohort Randomized Study of N-803, in Combination With Current Standard of Care VS Standard of Care as First-Line Treatment for Patients With Advanced or Metastatic NSCLC.

Actual Study Start Date :

May 18, 2018

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A (Experimental)	Drug: N-803 + Pembrolizumab The treatment plan in the experimental arm will consist of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen: Day 1, every 3 weeks: Pembrolizumab (200 mg intravenous infusion [IV]) N-803 (15 μg/kg subcutaneously [SC])
Experimental: Cohort B (Experimental)	Drug: N-803 + Carboplatin + Nab-paclitaxel + Pembrolizumab The treatment plan in the experimental arm of Cohort B will consist of an induction period of repeated 3-week cycles for 4 cycles then a maintenance period of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen: Induction (4 cycles): Day 1, every 3 weeks: Carboplatin (up to 900mg IV) Nab-paclitaxel (100mg/m² IV) Pembrolizumab (200mg IV) N-803 (15 μg/kg SC) Day 8: Nab-paclitaxel (100mg/m² IV) Day 15: Nab-paclitaxel (100mg/m² IV) Maintenance: Day 1, every 3 weeks: Pembrolizumab (200mg IV) N-803 (15 μg/kg SC)
Experimental: Cohort C (Experimental)	Drug: N-803 + Cisplatin or Carboplatin + Pembrolizumab + Pemetrexed The treatment plan in the experimental arm of Cohort C will consist of an induction period with repeated 3-week cycles for 4 cycles, then a maintenance period of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen: Induction (4 cycles): Day 1, every 3 weeks: Cisplatin (75mg/m²) or Carboplatin (up to 900mg IV) Pembrolizumab (200mg IV) Pemetrexed (500mg/m² IV) N-803 (15 μg/kg SC) Maintenance: Day 1, every 3 weeks: Pembrolizumab (200mg IV) N-803 (15 μg/kg SC)
Active Comparator: Cohort A (Control)	Drug: Pembrolizumab Drug: Pembrolizumab The reference treatment will consist of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen: Day 1, every 3 weeks: • Pembrolizumab (200 mg IV)
Active Comparator: Cohort B (Control)	Drug: Carboplatin + Nab-paclitaxel or Paclitaxel + Pembrolizumab The treatment plan in the control arm of Cohort B will consist of an induction period of repeated 3-week cycles for 4 cycles then a maintenance period of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen: Induction (4 cycles): Day 1, every 3 weeks: Carboplatin (up to 900mg IV) Nab-paclitaxel (100mg/m² IV) or Paclitaxel (200mg/m² IV) Pembrolizumab (200mg IV) Day 8: Nab-paclitaxel (100mg/m² IV) -if assigned to receive Day 15: Nab-paclitaxel (100mg/m² IV) -if assigned to receive Maintenance: Day 1, every 3 weeks: Pembrolizumab (200mg IV)
Active Comparator: Cohort C (Control)	Drug: Cisplatin or Carboplatin + Pembrolizumab + Pemetrexed The treatment plan in the control arm of Cohort C will consist of an induction period with repeated 3-week cycles for 4 cycles, then a maintenance period of repeated 3-week cycles for a maximum treatment period of 2 years, in accordance with the following dosing regimen: Induction (4 cycles): Day 1, every 3 weeks: Cisplatin (75mg/m²) or Carboplatin (up to 900mg IV) Pembrolizumab (200mg IV) Pemetrexed (500mg/m² IV) Maintenance: Day 1, every 3 weeks: Pembrolizumab (200mg IV)

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [24 Months]
Defined by RECIST Version 1.1 based on BICR

Secondary Outcome Measures

Overall Survival (OS) [24 Months]
Overall Response Rate (ORR) [24 Months]
Defined by RECIST Version 1.1 based on BICR
Duration of Response (DOR) [24 Months]
Defined by RECIST Version 1.1 based on BICR.
PFS [24 Months]
Defined by iRECIST based on BICR.
Overall Response Rate (ORR) [24 Months]
Defined by iRECIST based on BICR.
Duration of Response (DOR) [24 Months]
Defined by iRECIST based on BICR.
Disease Control Rate (DCR) [2 Months]
Confirmed CR, PR, or SD lasting for at least 2 months by RECIST Version 1.1 based on BICR
Quality of Life based on Patient Reported Outcomes Questionnaires [24 Months]
FACT-L

Other Outcome Measures

Incidence of treatment-emergent AEs and SAEs [24 Months]
Graded using the NCI CTCAE Version 5.0
Immunogenicity profile of N-803 in combination with pembrolizumab. [24 Months]
Detection of anti-drug antibodies
Tumor molecular profiles and correlations with subject outcomes [9 Weeks]
Genomic sequencing of tumor cells from tissue

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years old.
Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
Histologically-confirmed stage 3 or 4 NSCLC disease. Subjects with stage 3 disease must not be candidates for treatment with surgical resection or chemoradiation.
Subjects must not have received prior systemic chemotherapy for advanced or metastatic NSCLC. Previous neoadjuvant/adjuvant chemotherapy is allowed if completed ≥ 6 months before diagnosis of metastatic disease. Subject's with newly-diagnosed stage 4 NSCLC may have previously received systemic chemotherapy for stage 3 NSCLC.
For Cohort A only: NSCLC tumors must have PD-L1 expression (i.e. a TPS ≥1%) as determined by an FDA-approved test.
The subject's tumor must not harbor an EGFR sensitizing (activating) mutation or ALK translocation or targetable genomic aberration in BRAF, ROS1 or NTRK. EGFR sensitizing mutations are those mutations that are amenable to treatment with tyrosine kinase inhibitors including erlotinib, gefitinib, or afatinib. Investigators must be able to produce the source documentation of the EGFR mutation, ALK translocation, and BRAF, ROS1, and NTRK status. If any of the genomic changes described above are detected, additional information regarding the mutation status of other molecules is not required. If unable to test for these molecular changes, formalin fixed paraffin embedded tumor tissue of any age should be submitted to a central laboratory designated by the Sponsor for such testing. Subjects will not be randomized until the EGFR , BRAFT, ROS1, and NTRK mutation status and ALK translocation status is available in source documentation at the site.
ECOG performance status of 0 or 1.
Measurable tumor lesions according to RECIST 1.1.
Must be willing to release tumor biopsy specimen used for diagnosis of advanced or metastatic NSCLC (if available) for exploratory tumor molecular profiling. If tumor biopsy specimen is not available, subjects can still be enrolled.
Must be willing to provide blood samples prior to the start of treatment on this study for exploratory tumor molecular profiling analysis.
Must be willing to provide a tumor biopsy specimen 9 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, intrauterine devices (IUDs), hormonal therapy, 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.
A history of prior malignancy with the following exceptions: cancer treated with curative therapy with no disease recurrence for >3 years, non-metastatic prostate cancer controlled with hormonal therapy, or under observation; non-metastatic thyroid cancer; basal or squamous cell carcinoma of the skin, superficial bladder cancer, or in situ cervical cancer that has undergone successful definitive resection.
Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma).
History of organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroid use to manage AEs are permitted.
Prior systemic chemotherapy, major surgery, or thoracic radiation within 3 weeks of study initiation.
Requirement for other forms of anticancer treatment while on trial, including maintenance therapy, other radiation therapy, and/or surgery. Palliative radiation is permitted.
Known CNS metastases or carcinomatous meningitis. Subjects with previously treated, stable CNS metastases (no evidence of progression for ≥ 4 weeks, and resolution of neurologic symptoms to baseline state) are permitted in this study.
History of receiving a live vaccine 30 days prior to study treatment.
History of human immunodeficiency virus (HIV), or known active hepatitis B or C infection.
An active infection requiring systemic IV therapy.
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 < 1,500 cells/mm3.
Platelet count < 100,000 cells/mm3.
Total bilirubin greater the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])

1.5 × ULN.

Alkaline phosphatase (ALP) levels > 2.5 × ULN.
Serum creatinine > 2.0 mg/dL or 177 μmol/L or creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula)
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.
Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy.
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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Urological Institute - Alaska Clinical Research Center	Anchorage	Alaska	United States	99503
2	Genesis Cancer Center	Hot Springs	Arkansas	United States	71913
3	Chan Soon-Shiong Institute for Medicine	El Segundo	California	United States	90245
4	Adventist Health Glendale	Glendale	California	United States	92106
5	MemorialCare Health System	Long Beach	California	United States	90806
6	Adventist Health White Memorial	Los Angeles	California	United States	90033
7	Hoag Memorial Hospital	Newport Beach	California	United States	92663
8	Desert Hematology Oncology Medical Group	Rancho Mirage	California	United States	92270
9	Memorial Healthcare	Hollywood	Florida	United States	33021
10	Baptist Health South Florida - Miami Cancer Institute	Miami	Florida	United States	33176
11	Healthcare Research Network	Tinley Park	Illinois	United States	60487
12	Baptist Health - Lexington	Lexington	Kentucky	United States	40503
13	Baptist Health Louisville	Louisville	Kentucky	United States	40503
14	Karmanos Cancer Center	Detroit	Michigan	United States	48201
15	Mercy Research Joplin	Joplin	Missouri	United States	64804
16	Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center	Springfield	Missouri	United States	65804
17	St. Vincent Frontier Cancer Center	Billings	Montana	United States	59102
18	Astera Cancer Care	East Brunswick	New Jersey	United States	08816
19	University of Rochester	Rochester	New York	United States	14642
20	Stony Brooke Medicine	Stony Brook	New York	United States	11794
21	Mercy Research Oklahoma City	Oklahoma City	Oklahoma	United States	73120
22	LeHigh Valley	Allentown	Pennsylvania	United States	18103
23	Gettysburg Cancer Center	Gettysburg	Pennsylvania	United States	17325
24	Medical University of South Carolina (MUSC) - Hollings Cancer Center (HCC)	Charleston	South Carolina	United States	29425
25	Saint Francis Cancer Center/Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29607
26	Sanford Clinical Research	Sioux Falls	South Dakota	United States	57104
27	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
28	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
29	Baptist Cancer Center	Memphis	Tennessee	United States	38120
30	Texas Oncology-Austin	Austin	Texas	United States	78745
31	Texas Oncology-Bedford	Bedford	Texas	United States	76002
32	Oncology Consultants, PA	Houston	Texas	United States	77030
33	Bon Secours Richmond	Richmond	Virginia	United States	23114