QUILT-3.076: Study of Autologous M-CENK in Subjects With Locally Advanced or Metastatic Solid Tumors

NCT04898543 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: QUILT-3.076
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

This is a two-part, open-label phase 1 study to evaluate safety and preliminary efficacy of M-CENK Suspension for Infusion, Cryopreserved, and N-803 for subcutaneous administration in subjects with locally advanced or metastatic solid tumors. The study consists of two cohorts: cohort 1 includes subjects with either newly diagnosed solid tumors who have not received prior therapy or subjects who have received prior first line treatment; and cohort 2 that includes subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies. The two cohorts will be conducted simultaneously.

Conditions

Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (6)

• Primary Objective (cohort 1 and cohort 2, part A subjects): Determine the safety of mononuclear cell (MNC) apheresis collection by the number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to apheresis.

  \- Safety of apheresis collection as indicated by incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to apheresis, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, or in the case of cytokine release syndrome (CRS), using the specified grading system.

  Study Day 1, assessed for up to 1 week

• Primary Objective (cohort 1 and cohort 2, part A subjects): Determine the safety of mononuclear cell (MNC) apheresis collection by the number of participants with clinically significant laboratory tests.

  \- Clinical lab tests include hematology (CBC w/ differential (5 part) including platelet count) and chemistry panel (BUN, blood urea nitrogen; CBC, complete blood count; RBC, red blood cells; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase) performed within 1 calendar day prior to apheresis collection. Hematology test will be performed pre- and post- apheresis collection.

  From Baseline/Screening through Study Day 1, assessed for up to 1 day

• Primary Objective (cohort 1 and cohort 2, part A subjects): Determine the safety of mononuclear cell (MNC) apheresis collection by number of participants with abnormal vital signs.

  \- Vital signs to include temperature, respiratory rate, heart rate, blood pressure, and oxygen saturation

  From Baseline/Screening through Study Day 1, assessed for up to 28 days

• Primary Objective (cohort 2, part B subjects): Evaluate the overall safety profile of M-CENK and N-803 for SC administration by the number of TEAEs and SAEs after the first dose of M-CENK and the first dose of N-803 (M-CENK Dose Number 1)

  \- Incidence of TEAEs and SAEs, graded using the NCI CTCAE Version 5.0, or in the case of CRS using the specified grading system.

  From M-CENK Dose Number 1 up to 30 days, assessed for up to 30 days

• Primary Objective (cohort 2, part B subjects): Evaluate the overall safety profile of M-CENK and N-803 for SC administration by the number of participants with clinically significant laboratory tests

  \- Clinical lab tests include hematology (CBC w/ differential (5 part) including platelet count) and chemistry panel (BUN, blood urea nitrogen; CBC, complete blood count; RBC, red blood cells; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase) performed within 1 calendar day prior to first dose.

  From M-CENK Dose Number 1, assessed for up to 1 day

• Primary Objective (cohort 2, part B subjects): Evaluate the overall safety profile of M-CENK and N-803 for SC administration by the number of participants with abnormal vital signs

  \- Vital signs to include temperature, respiratory rate, heart rate, blood pressure, and oxygen saturation

  From M-CENK Dose Number 1, assessed for up to 1 day

Secondary Outcomes (10)

• Secondary Objective (cohort 1 and cohort 2, part A subjects): Evaluate the quantity and quality of the manufactured investigational cells from subjects in cohort 1 vs. cohort 2 by the number of MNCs for manufacturing M-CENK cells.

  Study Day 1

• Cohort 1 and cohort 2, part A subjects: Evaluate the quantity and quality of the manufactured cells from subjects in cohort 1 vs. cohort 2 by the number of MNCs collected and the % of natural killer (NK) cells.

  Study Day 1

• Cohort 1 and cohort 2, part A subjects: Evaluate the quantity and quality of the manufactured cells from subjects in cohort 1 vs. cohort 2 by the number, phenotype (CD56/CD16 positive and CD3 positive cells), and function of M-CENK cells.

  Study Day 1

• Secondary Objective (cohort 1 and cohort 2, part A subjects): Evaluate the quantity and quality of the manufactured investigational cells from subjects in cohort 1 vs. cohort 2 by the number of cryopreserved aliquots of manufactured M-CENK cells.

  Study Day 1

• Secondary Objective (cohort 2, part B): Evaluate the overall safety profile of up to 10 doses of M-CENK and up to 5 doses of N-803 for SC administration in subjects with relapsed or refractory (R/R) solid tumors by the number of TEAEs and SAEs.

  From M-CENK Dose Number 1 through End of Study (up to 12 months from first dose), assessed for up to 12 months

Other Outcomes (7)

• Exploratory Objective (cohort 1 and cohort 2, part A subjects): Evaluate and compare immune profiles of whole blood and apheresis product by frequency and phenotype of immune cells as measured by flow and mass cytometry..

  From Baseline/Screening through Study Day 1

• Exploratory Objective (cohort 1 and cohort 2, part A subjects): Evaluate and compare immune profiles of whole blood and apheresis product by frequency, number, phenotype, and proliferation of NK cells as measured by flow and mass cytometry.

  From Baseline/Screening through Study Day 1

• Cohort 1/2, part A subjects: Evaluate and compare immune profiles of whole blood and apheresis product by function of NK cells and NK cell receptor profile by intracellular staining for cytokines, surface marker staining, and assessments of cytotoxicity.

  From Baseline/Screening through Study Day 1

Study Arms (2)

Cohort 1: Subjects newly diagnosed no prior therapy or prior first line treatment

EXPERIMENTAL

Cohort 1: Subjects with either newly diagnosed solid tumors who have not received prior therapy or subjects who have received prior first line treatment. Cohort 1 may subsequently enroll in cohort 2 part B if they have progressive disease after ≥ 2 prior therapies or if they have progressive disease within 12 months of receiving neoadjuvant or adjuvant chemotherapy and meet the inclusion criteria for cohort 2 part B.

Other: Apheresis collection of MNCs (part A)

Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors

EXPERIMENTAL

Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies or not a candidate for therapy of proven efficacy for their disease.

Biological: M-CENK, Suspension for Infusion, Cryopreserved (M-CENK) (Cohort 2 part B); Biological: N-803 (Cohort 2 part B)

Interventions

M-CENK, Suspension for Infusion, Cryopreserved (M-CENK) (Cohort 2 part B) BIOLOGICAL

M-CENK will be administered up to 10 times weekly via intravenous (IV) infusion starting on study day 1 with a minimum of 7 days between each M-CENK dose. The dose of MCENK will be 0.25 - 0.75 × 10e9 cells per infusion.

Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors

N-803 (Cohort 2 part B) BIOLOGICAL

N-803 15 μg/kg will be administered subcutaneously prior to every other dose of M-CENK for up to 5 doses of N-803.

Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors

Apheresis collection of MNCs (part A) OTHER

Subjects in cohort 1A will participate in apheresis collection of lymphocytes (part A) and will not receive any investigational therapy in this study.

Cohort 1: Subjects newly diagnosed no prior therapy or prior first line treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohorts 1 and 2, Part A:
• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Have histologically confirmed locally advanced, unresectable, or metastatic solid tumor.
• For subjects with genetic mutations or alterations in solid tumors (e.g. NSCLC, pancreatic cancer, melanoma), the subjects must have received prior appropriate disease specific targeted therapy and have progressed.
• Have at least 1 measurable lesion and/or non-measurable disease evaluable in accordance with RECIST Version 1.1.
• For subjects with a history of human immunodeficiency virus (HIV)
• Subjects with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL and without a history of AIDS defining opportunistic infections.
• For subjects with a history of hepatitis B virus (HBV)
• Subjects who are chronic carriers of HBV infection (HBsAg-positive, undetectable or low HBV DNA, and normal ALT) who are not on HBV therapy, or in individuals who have serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and anti-HBc-positive), anti-HBV prophylaxis should be assessed prior to enrollment.
• Subjects with chronic HBV infection with active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy prior to enrollment.
• For subjects with a history of hepatitis C virus (HCV)
• Subjects with a history of HCV infection should have completed curative antiviral treatment and have a HCV viral load below the limit of quantification are eligible.
• Subjects who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible.
• Subjects on concurrent HCV treatment and have HCV below the limit of quantification are eligible.

You may not qualify if:

• \*Note: All subjects must meet eligibility criteria at the time of enrollment. Additionally, all subjects will be re-evaluated to confirm that they still meet the eligibility criteria specified with an asterisk below once the M-CENK cells are manufactured and prior to to the first administration of M-CENK. The Sponsor will approve the subject's continued eligibility prior to receiving the manufactured M-CENK cells.
• \*Life expectancy \< 16 weeks based on the best judgment of the Investigator.
• \*Involuntary weight loss of \> 10% usual body weight between the time of enrollment and at the time of administration of M-CENK cells
• \*Calorie or protein restrictive dietary regimen.
• \*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.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma) requiring medical treatment.
• \*Currently receiving or has received antibiotics since enrolling in the study or documented infection.
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), unless the inflammation is well controlled.
• \*Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count (ANC) \< 1000 cells/mm3.
• Platelet count \< 100,000 cells/mm3.
• Hemoglobin \< 9 g/dL.
• Total bilirubin \> 1.5 x the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
• AST (SGOT) or ALT (SGPT) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (2)

Chan Soon-Shiong Institute for Medicine

El Segundo, California, 90245, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Suspensions; Cryopreservation; ALT-803

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Tissue Preservation; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Preservation, Biological; Therapeutics; Investigative Techniques

Study Officials

• Leonard Sender, MD

  ImmunityBio, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 24, 2021
• Study Start: June 21, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: December 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)