Study of ADXS-504 Immunotherapy for Recurrent Prostate Cancer
Study Details
Study Description
Brief Summary
Primary:
• To evaluate the safety and tolerability of ADXS-504 and to determine the MTD or RP2D.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
ADXS-504 is a novel Listeria monocytogenes (Lm) - based immunotherapy, bioengineered to elicit T cell responses against 24 tumor antigens that include 1) 14 peptide antigens derived from frequently occurring and commonly shared hotspot mutations in patients with prostate cancer and 2) 10 peptide antigens derived from sequence-optimized TAAs that are differentially expressed or overexpressed in prostate cancer. ADXS-504 is designed to express multiple tumor antigen targets to which patients may generate a broad set of effector T cells for tumor control.
This is a Phase 1 open-label study of ADXS-504 monotherapy in subjects with biochemically recurrent prostate cancer previously treated with radical prostatectomy (RP) or radiation therapy (external beam or brachytherapy) who are not currently receiving androgen ablation therapy. The purpose of this study is to evaluate safety, tolerability, and preliminary clinical and immune responses following treatment with ADXS-504 monotherapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ADXS-504 Subjects with Biochemically Recurrent Prostate Cancer will receive ADXS-504 with dose escalation schema |
Drug: ADXS-504
ADXS-504 will be administered as monotherapy at 2 dose levels. Subjects who are assigned to receive DL1 will be administered ADXS-504 at a dose of 1×107 CFU q4 weeks (±3 days) from Week 1 to Week 21. Subjects who are assigned to receive DL2 will be administered ADXS-504 at a dose of 1×108 CFU q4 weeks (±3 days; Week 1 to Week 21). All 3-6 subjects must be enrolled in DL1, and DL1 must be confirmed safe, before enrollment for DL2 may begin. If DL1 is deemed to exceed the MTD, dose reduction of ADXS-504 to DL-1 (1×106 CFU) may proceed. Dose level -1, intermediate dose levels or expansion of a cohort may also be further evaluated if recommended by the Investigator and Advaxis in future amendments.
|
Outcome Measures
Primary Outcome Measures
- Safety and tolerability profile of ADXS-504 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v5.0 [28 days]
Rates of treatment-related adverse events (AEs), graded by CTCAE v5.0
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
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Age ≥ 18years at the time of consent.
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ECOG Performance Status of 0-1 within 28 days prior to registration.
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Histologically documented prostatic adenocarcinoma confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen.
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Previously undergone primary therapy for prostate cancer. Salvage external beam radiation or cryotherapy following primary therapy ≥ 6 months prior to randomization is allowed.
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Patients with low-risk biochemical recurrence, defined as a prostate specific antigen doubling time (PSADT) ≥10 months in patients who were previously treated with radical prostatectomy or radiation therapy
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A rising PSA defined as the following
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If the subject's primary therapy was radical prostatectomy (with or without adjuvant or salvage XRT), rising PSA is defined as 2 consecutive rising values above 0.2 ng/mL, each taken ≥ 3 weeks apart, and the last value ≥ 0.8 ng/mL
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If the subject received other primary therapies (e.g. XRT, cryosurgery, brachytherapy), rising PSA is defined per the Phoenix definition, i.e., 2 consecutive rising values above the PSA nadir plus 2.0 ng/mL.
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Testosterone ≥ 150 ng/dL ≤ 28 days of prior to registration
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Adequate bone marrow, hepatic, and renal function:
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ANC >1,500 cells/mm3
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Hemoglobin >9.0 g/dL
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Platelet count >100,000 cells/mm3
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Serum creatinine <2 × upper limit of normal (ULN)
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Serum total bilirubin <1.5 × ULN
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ALT <2.5 × ULN
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AST <2.5 × ULN
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Subject has baseline blood oxygen saturation on room air of ≥95%
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Subject is willing and able to provide an archived biopsy specimen which may be used for correlative studies and to determine HLA type;
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Subject with a female partner of child-bearing potential is eligible if he agrees to follow the contraceptive guidance, provided in the study, during the treatment period and for at least 120 days after the final dose of study treatment
Exclusion Criteria:
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Patients with evaluable metastatic disease on bone or computed tomography (CT) or PET scans performed ≤8 weeks of registration (patients with PET scan findings consistent with metastasis but who have normal conventional imaging by CT/MRI/Bone scan using standard radiographic criteria ARE eligible)
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Patients with known brain metastases
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Patients with active autoimmune disease requiring systemic treatment within the past 3 months, a documented history of clinically severe autoimmune disease, or a disorder that requires systemic corticosteroids or immunosuppressive agents
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Patients with active infection requiring systemic therapy or is dependent on or currently receiving antibiotics that cannot be discontinued before dosing. (Note: Subjects who discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last dose of antibiotic before receiving any study treatment
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Subject has a contraindication (e.g., sensitivity/allergy) to trimethoprim/ sulfamethoxazole and ampicillin
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Subject has uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical management
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Subject has a history of listeriosis
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Subject has an implanted medical device that poses a high risk for bacterial colonization and/or that cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screws, metal plates, bone grafts, or other exogenous implants). NOTE: More common devices and prosthetics that include arterial and venous stents, dental and breast implants and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device or implant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Columbia University Irving Medical Center | New York | New York | United States | 10032 |
Sponsors and Collaborators
- Mark Stein
Investigators
- Principal Investigator: Mark N. Stein, MD, Columbia University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AAAT0847