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History of Changes for Study: NCT06056791
Study of INKmune in Patients With mCRPC (CaRe Prostate) (CaRe)
Latest version (submitted February 20, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 22, 2023 None (earliest Version on record)
2 September 27, 2023 Outcome Measures and Study Status
3 January 8, 2024 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 February 20, 2024 Study Status and Contacts/Locations
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Changes (Merged) for Study: NCT06056791
September 27, 2023 (v2) -- January 8, 2024 (v3)

Changes in: Study Status, Oversight and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: INMB-INB16-003
Brief Title: Study of INKmune in Patients With mCRPC (CaRe Prostate) (CaRe)
Official Title: An Open-label, Phase I/IIa Dose Escalation and Expansion Study to Determine the Safety and Clinical Activity of an Immune Priming Cell Therapy (INKmune) in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Secondary IDs:
Open or close this module Study Status
Record Verification: September 2023 January 2024
Overall Status: Not yet recruiting Recruiting
Study Start: November 30, 2023
Primary Completion: May 30, 2025 [Anticipated]
Study Completion: November 30, 2025 [Anticipated]
First Submitted: August 7, 2023
First Submitted that
Met QC Criteria:
September 22, 2023
First Posted: September 28, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:
September 27, 2023 January 8, 2024
Last Update Posted: September 29, 2023 [Actual] January 10, 2024 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Inmune Bio, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: This is an open-label, phase I/IIa dose escalation and expansion study of INKmune in men with mCRPC. INKmune is administered to patients intravenously over three doses, at least one-week apart. The study will consist of two stages.
Detailed Description:

This is an open-label, phase I/IIa dose escalation and expansion study of INKmune in men with mCRPC. INKmune is administered to patients intravenously over 3 doses. The 3 infusions will occur over a minimum of a 2-week period, with each infusion at least 1 week apart. The study will consist of 2 stages:

  • Dose escalation: exploring dose levels of 1x10^8, 3x10^8 and 5x10^8 cells per infusion (18 patients projected).
  • Dose expansion: following mBOIN termination and maximum tolerated dose (MTD) identification, 12 patients will be enrolled in up to 2 candidate optimal dose levels for final optimal dose determination.

Eligible patients will sign informed consent prior to any study assessments being performed. Patients have up to 30 days in which to have all screening procedures and eligibility assessed. Patients will be infused with INKmune on Days 1, 8 and 15. Patients will also present to site on days 29, 57, 85, 113 and 141 to complete study assessments. Day 169 is the last study visit and patient will have completed trial after this visit has been completed. Option to enroll in the INKmune Long term Follow-up Registry will be presented at Day 169 visit.

Open or close this module Conditions
Conditions: Cancer
Metastatic Castration-resistant Prostate Cancer
mCRPC
Keywords: mCRPC
NK Cell Based Therapy
Immune Mediated Therapy
Cell Therapy
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
Dose escalation using mBOIN design
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort 1: 1 x 10^8 INKmune

In Dose Escalation: INKmune therapy will be administered by a slow intravenous injection via conventional blood giving set. Approximately 18 patients will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15 as per the below:

  • In Cohort 1, the initial planned dose is 1 x 10^8 INKmune;
  • In Cohort 2, the weekly dose will increase to 3 x 10^8 INKmune;
  • In Cohort 3, the weekly dose will increase to 5 x 10^8 INKmune.

In Dose Expansion: INKmune therapy will be administered by a slow intravenous injection via conventional blood giving set. Approximately 12 patients will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15 as per the below:

Following mBOIN termination and MTD identification, patients will be enrolled in up to two candidate optimal dose levels (no higher than the MTD) for final optimal dose determination.

Biological: INKmune
INKmune is a patented biologic delivery system and method for cancer treatment using in vivo priming and activation of natural killer (NK) cells in order to achieve tumor cell lysis. INKmune is a suspension of INB16 cells which have been rendered replication incompetent that does not require donor matching.
Experimental: Cohort 2: 3 x 10^8 INKmune

In Dose Escalation: INKmune therapy will be administered by a slow intravenous injection via conventional blood giving set. Approximately 18 patients will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15 as per the below:

  • In Cohort 1, the initial planned dose is 1 x 10^8 INKmune;
  • In Cohort 2, the weekly dose will increase to 3 x 10^8 INKmune;
  • In Cohort 3, the weekly dose will increase to 5 x 10^8 INKmune.

In Dose Expansion: INKmune therapy will be administered by a slow intravenous injection via conventional blood giving set. Approximately 12 patients will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15 as per the below:

Following mBOIN termination and MTD identification, patients will be enrolled in up to two candidate optimal dose levels (no higher than the MTD) for final optimal dose determination.

Biological: INKmune
INKmune is a patented biologic delivery system and method for cancer treatment using in vivo priming and activation of natural killer (NK) cells in order to achieve tumor cell lysis. INKmune is a suspension of INB16 cells which have been rendered replication incompetent that does not require donor matching.
Experimental: Cohort 3: 5 x 10^8 INKmune

In Dose Escalation: INKmune therapy will be administered by a slow intravenous injection via conventional blood giving set. Approximately 18 patients will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15 as per the below:

  • In Cohort 1, the initial planned dose is 1 x 10^8 INKmune;
  • In Cohort 2, the weekly dose will increase to 3 x 10^8 INKmune;
  • In Cohort 3, the weekly dose will increase to 5 x 10^8 INKmune.

In Dose Expansion: INKmune therapy will be administered by a slow intravenous injection via conventional blood giving set. Approximately 12 patients will receive 3 weekly IV doses of INKmune on Day 1, 8, and 15 as per the below:

Following mBOIN termination and MTD identification, patients will be enrolled in up to two candidate optimal dose levels (no higher than the MTD) for final optimal dose determination.

Biological: INKmune
INKmune is a patented biologic delivery system and method for cancer treatment using in vivo priming and activation of natural killer (NK) cells in order to achieve tumor cell lysis. INKmune is a suspension of INB16 cells which have been rendered replication incompetent that does not require donor matching.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.
[ Time Frame: 2-3 years ]

Measurement of peripheral blood activated NK cell (memory like NK cell phenotype) percentage by flow cytometry to >2 times pre-treatment percentage.
2. Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.
[ Time Frame: 2-3 years ]

Measurement of Prostate Specific Antigen (PSA) to determine the percent of patients that decrease PSA by ≥30% during treatment.
3. Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.
[ Time Frame: 2-3 years ]

Measurement of disease burden as determined by prostate-specific membrane antigen (PMSA) positron emission tomography (PET) scan.
4. Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.
[ Time Frame: 2-3 years ]

Measurement of change in circulating tumor DNA (ctDNA).
5. Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.
[ Time Frame: 2-3 years ]

Measurement of frequency and severity of Dose-Limiting Toxicities (DLT).
6. Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.
[ Time Frame: 2-3 years ]

MTD identification, if available.
7. Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.
[ Time Frame: 2-3 years ]

Measurement of frequency and severity of adverse events (AEs).
8. Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.
[ Time Frame: 2-3 years ]

Measurement of frequency and severity of serious adverse events (SAEs).
Secondary Outcome Measures:
1. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing RECIST.
[ Time Frame: 2-3 years ]

Assessment based on current Prostate Cancer Working Group 3 (PCWG3) modified Response Evaluation Criteria (RECIST) Version 1.1, where applicable.
2. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing PSA.
[ Time Frame: 2-3 years ]

Measurement of PSA response using PSA50 response rate.
3. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing PSA.
[ Time Frame: 2-3 years ]

Measurement of the period of time PSA decrease by ≥30%.
4. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing PSA.
[ Time Frame: 2-3 years ]

Measurement of the period of time PSA is below baseline.
5. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing survival data.
[ Time Frame: 2-3 years ]

Measurement of Progression Free Survival (PFS).
6. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing survival data.
[ Time Frame: 2-3 years ]

Measurement of Radiological Progression Free Survival (rPFS).
7. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing disease response.
[ Time Frame: 2-3 years ]

Measurement of Objective response rate (ORR)
8. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing disease response.
[ Time Frame: 2-3 years ]

Measurement of the Disease control rate.
9. Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing survival data.
[ Time Frame: 2-3 years ]

Measurement of Overall survival (OS).
Other Outcome Measures:
1. Assess persistence of memory like Natural Killer (NK) cell number.
[ Time Frame: 2-3 years ]

Assess persistence of memory like Natural Killer (NK) cell number.
2. Explore the relationship between persistence of INKmune cells in patients treated with INKmune and disease response experienced through Day 169.
[ Time Frame: 1-169 Days ]

Relationship will be explored through multi-parameter flow cytometry and tumor killing of NK resistant tumor targets (RAJI cells) in blood of patients after treatment with INKmune. Disease response will be assessed from RECIST, PSMA, PSA data.
3. Determine change in blood PSA levels compared to change in tumor burden, as assessed by RECIST v1.1 and PSMA PET scan, for each patient treated with INKmune.
[ Time Frame: 1-169 Days ]

Relationship between blood PSA levels and change in tumor burden will be assessed through collection of serum PSA level and measurable disease burden assessed by RECIST v1.1, PCWG3 criteria and 18F-PSMA PET scan (Piflufolastat). PSA will be collected at Screening and at each visit following the 3 doses of INKmune. PSMA PET scans will be completed at Day 1, Day 57 and Day 169.
4. Determine the concentration of circulating tumor DNA (ctDNA) levels and treatment response in patients with ctDNA data.
[ Time Frame: 1-169 Days ]

Relationship between ctDNA levels and treatment response will be assessed by collection of serial ctDNA assays in patients with available pre-treatment tumor DNA. ctDNA collections will occur at Day 1, Day 57 and Day 169.
5. Determine endogenous NK cell infiltration from optional biopsy tissue and previously resected tissue (if available).
[ Time Frame: 2-3 years ]

Optional biopsy tissue and previously resected tissue will be analyzed with Immunohistochemistry (IHC) and RNA sequencing of patient pathological specimens.
6. Determine stromal expression of inhibitory ligands from optional biopsy tissue and previously resected tissue (if available).
[ Time Frame: 2-3 years ]

Optional biopsy tissue and previously resected tissue will be analyzed with Immunohistochemistry (IHC) and RNA sequencing of patient pathological specimens.
7. Complete transcriptomic analyses from optional biopsy tissue and previously resected tissue (if available).
[ Time Frame: 2-3 years ]

Optional biopsy tissue and previously resected tissue will be analyzed with Immunohistochemistry (IHC) and RNA sequencing of patient pathological specimens.
8. Evaluate activity of INKmune therapy in relation to the sequence of mCRPC treatment received by patients.
[ Time Frame: 2-3 years ]

Outcome will be evaluated by review of medical history and collection of safety follow-up visits to record mCRPC treatments after completion of clinical trial in comparison to peripheral blood activated NK cell (memory like NK cell phenotype) percentage by flow cytometry.
9. Assess the experience of clinical trial participation by patients through a comprehensive patient survey provided post visit at 3 timepoints during the trial.
[ Time Frame: 1-2 years ]

Quality Improvement: Assess the experience of clinical trial participation by patients through patient questionnaires collected throughout the clinical trial. Questionnaires will be provided at 3 time points during study participation following study visits.

Understand the patient experiences across participation in the clinical trial, through patient questionnaires (answers to be selected on a scale from '1 to 5', with '1' being very poor and '5' being very good), to assess patient perceptions in the following areas:

  • Access,
  • Communication,
  • Information & materials,
  • Patient burden,
  • Patient centeredness,
  • Privacy,
  • Quality of care,
  • Trust,
  • Safety.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Male
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Male subjects over 18 years of age at time of screening.
  2. Blood Prostate Specific Antigen (PSA) of >1.0 ng/ml at time of screening.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 at time of screening.
  4. Histologic confirmation of adenocarcinoma prostate cancer.
  5. A diagnosis of progressive metastatic castrate resistant prostate cancer (mCRPC), as defined by Prostate Cancer Clinical Trials Working Group 3 (PCWG3), following androgen deprivation therapy (ADT) and at least one androgen receptor signaling inhibitor, but not more than 3 therapies in addition to ADT. Progressive disease at the time of study entry as indicated by at least one of the following: i. At least two rising PSA values at a minimum of a one-week interval. If PSA is the only measure of progression, then the minimum PSA value at the start of treatment must be ≥ 1 ng/mL. ii. Radiographic progression per RECIST1.1 for soft tissue (at least 1 measurable lesion per RECIST 1.1), and/or iii. Progression of bone metastases.
  6. Castrate level of testosterone of < 50 ng/dL.
  7. Adequate organ function indicated by the following laboratory parameters:

    i. Hemoglobin ≥ 8.0 g/dL. ii. White Blood Cell Count (WBC) ≥ 3.0 x 10⁹/L. iii. Lymphocytes ≥ 80% LLN iv. Absolute Neutrophil Count (ANC) ≥ 1.5 x 10⁹/L. v. Platelets ≥ 100 x 10⁹/L. vi. PT and APTT < 1.5x ULN (unless receiving therapeutic anticoagulation). vii. AST or ALT ≤ 2.5x ULN. AST or ALT ≤ 5x ULN for patients with liver metastases.

    viii. Bilirubin < 1.5x ULN (< 3x ULN in Gilbert's Syndrome). ix. Creatinine clearance/estimated GFR ≥ 50 mL/min (MDRD or Cockcroft-Gault). x. Resting room air PaO2 saturation of >95% as measured by pulse oximetry.

  8. Negative screen for Human Immunodeficiency virus (HIV), Hepatitis B virus (HBV) antigen, and Hepatitis C virus (HCV). If testing was done within the past three months, there is no need to repeat testing if documentation of results is provided to the study site.
  9. Subjects and their partners of reproductive potential must agree to use an effective form of contraception during the period of drug administration and for three months following the completion of the last administration of the study drug. An effective form of contraception is defined as oral contraceptives plus one form of barrier method or double barrier methods (condom with spermicide or condom with diaphragm).
  10. Subjects must be able to understand the potential risks and benefits of the study and be able to read and give written informed consent.

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

  1. Diagnosis of small cell/neuroendocrine prostate cancer. Immunohistochemical staining for neuroendocrine markers (e.g., chromogranin A, neuron-specific enolase, and synaptophysin) is not sufficient to establish a small cell/neuroendocrine histology; morphologic features that are characteristic of small cell/neuroendocrine prostate cancer are required to confirm the presence of small cell/neuroendocrine prostate cancer.
  2. History of concurrent malignant cancer within previous 3 years, with the exception of in situ carcinomas and non-melanoma skin cancer.
  3. Uncontrolled autoimmune disease including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, temporal arteritis, and thyroiditis. Autoimmune conditions that are well-controlled in the opinion of the investigator must first be discussed with the Sponsor prior to enrollment.
  4. A requirement for daily systemic corticosteroids for any reason; or other immunosuppressive or immunomodulatory agents. Topical, nasal, modified-release oral, and/or physiologic corticosteroids may be permitted following discussion with the Sponsor.
  5. Clinically significant cardiac disease (New York Heart Association Class III/IV) or severe debilitating pulmonary disease.
  6. Patients with a current or recent history, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological, or neurological disease.
  7. Cytotoxic chemotherapy within three weeks prior to start of study treatment (Day 1).
  8. Radiation therapy within two weeks prior to start of study treatment (Day 1).
  9. Patients may not have received a previous NK based therapy.
  10. Evidence of central nervous system (CNS) metastatic disease at screening.
  11. Patients with an active infection requiring antibiotic treatment within seven days of starting study treatment (Day 1).
  12. Administration of live attenuated vaccines within eight weeks of start of study treatment (Day 1) and throughout the study.
  13. Any other medical condition that in the opinion of the Investigator may interfere with a subject's participation in, or compliance with, the study
  14. Participation in a therapeutic research study or receipt of an investigational drug within 4 weeks of start of treatment (Day 1) or 5 half-lives, whichever occurs first.
  15. Expected survival of less than six months
Open or close this module Contacts/Locations
Central Contact Person: Nicole Kay-Mindick
Telephone: 386 852 2361
Email: nmindick@inmunebio.com
Study Officials: Tara Lehner
Study Director
INmune Bio
Locations: United States, California
VA Greater Los Angeles Healthcare System
[Not yet recruiting]
Los Angeles, California, United States, 90073
Contact:Principal Investigator: Matthew Rettig, MD
University of California, Los Angeles
[Not yet recruiting]
Los Angeles, California, United States, 90095
Contact:Principal Investigator: Matthew Rettig, MD
United States, Nevada
Comprehensive Cancer Centers of Nevada
[Not yet recruiting]
Las Vegas, Nevada, United States, 89169
Contact:Principal Investigator: Kyaw Thein, MD
United States, Ohio
Carl & Edyth Lindner Center for Research and Education at The Christ Hospital and The Christ Hospital Cancer Center
[Recruiting]
Cincinnati, Ohio, United States, 45219
Contact:Principal Investigator: Alexander Starodub, MD
United States, Texas
Renovatio Clinical
[Not yet recruiting]
El Paso, Texas, United States, 79915
Contact:Principal Investigator: Haroutioun Shahinian, MD
Renovatio Clinical
[Recruiting]
The Woodlands, Texas, United States, 77380
Contact:Principal Investigator: Jonathan Lu, MD
United States, Virginia
NEXT Virginia
[Not yet recruiting]
Fairfax, Virginia, United States, 22031
Contact:Principal Investigator: Mahamed Salkeni, MD
United States, Washington
VA Puget Sound Health Care System
[Not yet recruiting]
Seattle, Washington, United States, 98108
Contact:Principal Investigator: Robert (Bruce) Montgomery, MD
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
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Links: Description: Tracy, C. (2022). Prostate Cancer Treatment & Management: Approach Considerations, Localized Prostate Cancer, Management of Advanced and Metastatic Disease.
Description: FDA (2021). Drug Development Tools: Fit-for-Purpose Initiative
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