Study of INKmune in Patients With mCRPC (CaRe Prostate)

Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06056791
• Other study ID #: INMB-INB16-003
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 30, 2023
• Est. completion date: November 30, 2025

Study information

• Verified date: March 2024
• Source: Inmune Bio, Inc.
• Contact: Nicole Kay-Mindick
• Phone: 386 852 2361
• Email: nmindick[@]inmunebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

• Dose expansion: following mBOIN termination and maximum tolerated dose (MTD) identification, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 10?/L.

• iii. Lymphocytes = 80% LLN

• iv. Absolute Neutrophil Count (ANC) = 1.5 x 10?/L.

• v. Platelets = 100 x 10?/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 = 30 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. If diagnosis or treatment for other cancers have occurred in the last 3 years, further discussion needed.

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

16. At the time of consent, unable to comply with study procedures and assessments.

Related Conditions & MeSH terms

• Cancer
• mCRPC
• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Carl & Edyth Lindner Center for Research and Education at The Christ Hospital and The Christ Hospital Cancer Center	Cincinnati	Ohio
United States	Renovatio Clinical	El Paso	Texas
United States	NEXT Virginia	Fairfax	Virginia
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of California, Los Angeles	Los Angeles	California
United States	VA Greater Los Angeles Healthcare System	Los Angeles	California
United States	VA Puget Sound Health Care System	Seattle	Washington
United States	Renovatio Clinical	The Woodlands	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Inmune Bio, Inc.

Country where clinical trial is conducted

United States, 

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* Note: There are 58 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess persistence of memory like Natural Killer (NK) cell number.	Assess persistence of memory like Natural Killer (NK) cell number.	2-3 years
Other	Explore the relationship between persistence of INKmune cells in patients treated with INKmune and disease response experienced through Day 169.	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.	1-169 Days
Other	Determine change in blood PSA levels compared to change in tumor burden, as assessed by RECIST v1.1, and Pylarify PSMA PET scan (piflufolastat F 18) for each patient treated with INKmune.	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 Pylarify PSMA PET scan (piflufolastat F 18). 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.	1-169 Days
Other	Determine the concentration of circulating tumor DNA (ctDNA) levels and treatment response in patients with ctDNA data.	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.	1-169 Days
Other	Determine endogenous NK cell infiltration from optional biopsy tissue and previously resected tissue (if available).	Optional biopsy tissue and previously resected tissue will be analyzed with Immunohistochemistry (IHC) and RNA sequencing of patient pathological specimens.	2-3 years
Other	Determine stromal expression of inhibitory ligands from optional biopsy tissue and previously resected tissue (if available).	Optional biopsy tissue and previously resected tissue will be analyzed with Immunohistochemistry (IHC) and RNA sequencing of patient pathological specimens.	2-3 years
Other	Complete transcriptomic analyses from optional biopsy tissue and previously resected tissue (if available).	Optional biopsy tissue and previously resected tissue will be analyzed with Immunohistochemistry (IHC) and RNA sequencing of patient pathological specimens.	2-3 years
Other	Evaluate activity of INKmune therapy in relation to the sequence of mCRPC treatment received by patients.	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.	2-3 years
Other	Assess the experience of clinical trial participation by patients through a comprehensive patient survey provided post visit at 3 timepoints during the trial.	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.	1-2 years
Primary	Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.	Measurement of peripheral blood activated NK cell (memory like NK cell phenotype) percentage by flow cytometry to >2 times pre-treatment percentage.	2-3 years
Primary	Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.	Measurement of Prostate Specific Antigen (PSA) to determine the percent of patients that decrease PSA by =30% during treatment.	2-3 years
Primary	Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.	Measurement of disease burden as determined by prostate-specific membrane antigen (PMSA) positron emission tomography (PET) scan.	2-3 years
Primary	Determine the optimal concentration of INKmune therapy to be used in patients with mCRPC.	Measurement of change in circulating tumor DNA (ctDNA).	2-3 years
Primary	Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.	Measurement of frequency and severity of Dose-Limiting Toxicities (DLT).	2-3 years
Primary	Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.	MTD identification, if available.	2-3 years
Primary	Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.	Measurement of frequency and severity of adverse events (AEs).	2-3 years
Primary	Evaluate the safety and tolerability of INKmune therapy in patients with mCRPC.	Measurement of frequency and severity of serious adverse events (SAEs).	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing RECIST.	Assessment based on current Prostate Cancer Working Group 3 (PCWG3) modified Response Evaluation Criteria (RECIST) Version 1.1, where applicable.	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing PSA.	Measurement of PSA response using PSA50 response rate.	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing PSA.	Measurement of the period of time PSA decrease by =30%.	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing PSA.	Measurement of the period of time PSA is below baseline.	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing survival data.	Measurement of Progression Free Survival (PFS).	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing survival data.	Measurement of Radiological Progression Free Survival (rPFS).	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing disease response.	Measurement of Objective response rate (ORR)	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing disease response.	Measurement of the Disease control rate.	2-3 years
Secondary	Evaluate the overall clinical efficacy of INKmune treatment in patients utilizing survival data.	Measurement of Overall survival (OS).	2-3 years

External Links

•   FDA (2021). Drug Development Tools: Fit-for-Purpose Initiative
•   Tracy, C. (2022). Prostate Cancer Treatment & Management: Approach Considerations, Localized Prostate Cancer, Management of Advanced and Metastatic Disease.