QUILT-3.076: Study of Autologous M-CENK in Subjects With Locally Advanced or Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
This is a two-part, open-label phase 1 study to evaluate safety and preliminary efficacy of M-CENK and N-803 for subcutaneous administration, cryopreserved in subjects with locally advanced or metastatic solid tumors. The study consists of two cohorts: cohort 1 includes subjects with newly diagnosed high-risk solid tumors who have not received prior treatment for high-risk tumors; and cohort 2 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: Subjects newly diagnosed Cohort 1: Subjects newly diagnosed with high-risk solid tumors who have not received treatment. |
Other: Apheresis collection of lymphocytes (part A)
Subjects in cohort 1 will participate in apheresis collection of lymphocytes (part A) and will not receive any investigational therapy in this study.
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| Experimental: Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors Cohort 2: Subjects with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies. |
Biological: M-CENK, Suspension for Infusion, Cryopreserved (M-CENK)
M-CENK will be administered 4 times via intravenous (IV) infusion on days 1, 8, 15 and 22. The dose of MCENK will be 0.25 - 0.75 × 10e9 cells per infusion.
Biological: N803
N803 15 μg/kg will be administered subcutaneously on days 1 and 15.
|
Outcome Measures
Primary Outcome Measures
- Study Endpoints (cohort 1 and cohort 2, part A subjects): Safety of apheresis collection [from baseline to study day 1]
Safety of apheresis procedure for collection of 2 blood volumes. AEs and SAEs will be measured using CTCAE Version 5. For example, the incidence, severity, and management of AEs or SAEs will be reported.
- Study Endpoints (for cohort 2, part B subjects only): Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs) [through Day 203]
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), 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 defined in Section 5.1.11.
Secondary Outcome Measures
- Study Endpoints (cohort 1 and cohort 2, part A subjects): Number of MNCs for manufacturing M-CENK cells [From baseline to Week 1]
Number of MNCs for manufacturing M-CENK cells.
- Study Endpoints (cohort 1 and cohort 2, part A subjects): Number of MNC collected and the percentage of NK Cells (CD56/CD16 positive cells) [From baseline to Week 1]
Number of MNC collected and the percentage of NK Cells (CD56/CD16 positive cells) after a two blood volume apheresis procedure for collection. The cell count and viability will be measured using an automated cell counter. The percentage of cells that are CD56/CD16 positive will be measured using flow cytometry.
- Study Endpoints (cohort 1 and cohort 2, part A subjects): Number of MNC collected and the percentage of NK Cells (CD3 cells) [From baseline to Week 1]
Number of MNC collected and the percentage of NK Cells (CD3 cells) after a two blood volume apheresis procedure for collection. The cell count and viability will be measured using an automated cell counter. The percentage of cells that are CD3 positive will be measured using flow cytometry.
- Study Endpoints (cohort 1 and cohort 2, part A subjects): Number, phenotype, and function of M-CENK cells [from baseline to Week 4]
Number, phenotype, and function of M-CENK cells following enrichment and expansion of the NK cells ex-vivo. Phenotype and cell functionality will be measured using flow cytometry. The expected outcome is for a functional product with high viability.
- Study Endpoints (cohort 1 and cohort 2, part A subjects): Aliquot and manufacture cryopreserved M-CENK cells [from baseline to Week 4]
Aliquot and manufacture cryopreserved M-CENK cells ahead of use in a clinical protocol adoptive transfer correlated with clinical end points.
- Study Endpoints (for cohort 2, part B subjects only): ORR [through Day 203]
ORR in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and modified RECIST guidelines for immunotherapy trials (iRECIST)
- Study Endpoints (for cohort 2, part B subjects only): PFS [through Day 203]
PFS by RECIST Version 1.1 and iRECIST
- Study Endpoints (for cohort 2, part B subjects only): OS [through Day 203]
OS will be evaluated using Kaplan-Meier methods. OS will be defined as the time from the date of first treatment to the date of death (any cause). Subjects who are alive at the end of follow-up will be censored at the last known date alive.
- Study Endpoints (for cohort 2, part B subjects only): Laboratory tests [through Day 203]
Incidence of abnormal changes of laboratory tests include hematology and chemistry panel
- Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Temperature [through Day 203]
Changes in vital signs from Grades 1-4: measured in (°C) or (°F)
- Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Heart Rate [through Day 203]
Changes in vital signs from Grades 1-4: measured by how many heart beats per minute
- Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Blood Pressure [through Day 203]
Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg
- Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Oxygen Saturation [through Day 203]
is measured by Pulse Oxymetry
- Study Endpoints (for cohort 2, part B subjects only): Vital Signs - Respiratory Rate [through Day 203]
Changes in vital signs from Grades 1-4: measured in how many breaths per minute
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years old.
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Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
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Have histologically confirmed unresectable, locally advanced or metastatic solid tumor.
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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.
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For subjects with a history of HIV
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Subjects with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL and without a history of AIDS defining opportunistic infections are eligible.
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For subjects with a history of HBV
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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.
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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.
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For subjects with a history of HCV
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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.
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Subjects who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible.
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Subjects on concurrent HCV treatment and have HCV below the limit of quantification are eligible.
Note: Subjects who have a history of HIV/HBV/HCV or are seropositive will require Infectious Disease Marker (IDM) testing prior to apheresis collection.
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Subjects with previously treated and who currently have non-progressive brain metastasis may participate in this study.
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Able to undergo an Apheresis procedure:
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Has adequate venous access
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Able to sit or recline for 5-6 hours with limited movement
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Hemoglobin must be ≥ 9.0 g/dL
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Platelet count must be ≥ 100 cells/mm3
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Vital signs must be within normal range
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Negative pregnancy test for females of childbearing potential.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Cohort 2 subjects only:
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Have received treatment with at least 2 prior lines of therapy in the metastatic setting or not be a candidate for therapy of proven efficacy for their disease. Prior immune therapy and prior treatment with a checkpoint inhibitor as per FDA indication for current standard of care therapy is allowed.
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Have at least 1 measurable lesion and/or non-measurable disease evaluable in accordance with RECIST Version 1.1.
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Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
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Agreement to practice effective contraception for female subjects of child-bearing potential and nonsterile males.
Exclusion Criteria:
Cohort 2 subjects only:
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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.
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Currently receiving antibiotics for a recent infection.
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Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma) requiring medical treatment
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History of organ transplant requiring immunosuppression.
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History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), unless the inflammation is well controlled.
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Inadequate organ function, evidenced by the following laboratory results:
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Absolute neutrophil count (ANC) < 1500 cells/mm3.
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Platelet count < 100,000 cells/mm3.
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Hemoglobin < 9 g/dL.
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Total bilirubin greater than 1.5 x the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
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Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).
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Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN in subjects with bone metastases).
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Serum creatinine > 2.0 mg/dL or 177 μmol/L.
Note: Each site should use its own institution's upper limit of normal (ULN) to determine eligibility.
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For subjects who have received approved chemotherapy or approved immunotherapy, a repeat CBC a least 14 days after completion of the treatment to demonstrate recovery of counts to an ANC ≥1000 and Platelets ≥100,000 is required.
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For subjects who have received investigational chemotherapy or investigational immunotherapy, a repeat CBC a least 30 days after completion of the treatment to demonstrate recovery of counts to an ANC ≥ 1000 and Platelets ≥ 100,000 is required.
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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.
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Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy. Oxygen therapy on an as needed or intermittent basis is allowed.
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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.
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Known hypersensitivity to any component of the study medication(s).
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Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
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Concurrent participation in any interventional clinical trial.
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Pregnant and nursing women. A negative serum pregnancy test during screening and a negative pregnancy test within 72 hours prior to the first dose must be documented before M-CENK is administered to a female subject of childbearing potential.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chan Soon-Shiong Institute for Medicine | El Segundo | California | United States | 90245 |
| 2 | Hoag Memorial Hospital Presbyterian | Newport Beach | California | United States | 92663 |
Sponsors and Collaborators
- ImmunityBio, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- QUILT-3.076