Clinical Trials /

Use of Ligand-Inducible Autologous T Cells Engineered to Target PSCA on Tumor Cells in Selected Advanced Solid Tumors

NCT02744287

Description:

The purpose of this study is to evaluate the safety and activity of BPX-601 in participants with previously treated advanced solid tumors (pancreatic, stomach, or prostate) expressing high levels of prostate stem cell antigen (PSCA). Participants' T cells are modified to recognize and target the PSCA tumor marker on cancer cells.

Related Conditions:
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Use of Ligand-Inducible Autologous T Cells Engineered to Target PSCA on Tumor Cells in Selected Advanced Solid Tumors
  • Official Title: A Phase 1/2 Feasibility, Safety, and Activity Study of PSCA-Specific Chimeric Antigen Receptor Engineered T Cells (BPX-601) in Subjects With Previously Treated Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BP-012
  • NCT ID: NCT02744287

Conditions

  • Pancreatic Adenocarcinoma
  • Gastric Adenocarcinoma
  • Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
BPX-601Arm 1: Part 1 Dose Escalation
RimiducidAP1903Arm 1: Part 1 Dose Escalation

Purpose

The purpose of this study is to evaluate the safety and activity of BPX-601 in participants with previously treated advanced solid tumors (pancreatic, stomach, or prostate) expressing high levels of prostate stem cell antigen (PSCA). Participants' T cells are modified to recognize and target the PSCA tumor marker on cancer cells.

Detailed Description

      The goal of this study is to characterize the feasibility, safety, and clinical activity of
      PSCA-specific CAR-T cells, BPX-601, administered with rimiducid to subjects with previously
      treated, PSCA-positive advanced solid tumors (pancreatic, stomach, or prostate). BPX-601
      CAR-T cells are genetically engineered to express a rimiducid-inducible signaling domain
      which functions as a molecular switch to enhance activation and proliferation.

      Part 1 (Phase 1): Cell dose escalation to identify the maximum dose of BPX-601 T cells
      (escalating doses from 1.25 x 10E6 cells/kg up to 5.0 x 10E6 cells/kg to be explored)
      administered with rimiducid (fixed single-dose at 0.4 mg/kg).
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Part 1 Dose EscalationExperimentalParticipants with advanced pancreas, stomach, or prostate cancer will receive an intravenous infusion of BPX-601 followed by an intravenous infusion of rimiducid. Dose escalation of BPX-601 will continue until the recommended cell dose level is reached.
  • BPX-601
  • Rimiducid
Arm 2: Parts 2 and 3 Dose ExpansionExperimentalParticipants with advanced pancreas, stomach, or prostate cancer will receive an intravenous infusion of BPX-601 at the recommended cell dose level followed by an intravenous infusion of rimiducid.
  • BPX-601
  • Rimiducid

Eligibility Criteria

        Inclusion Criteria:

          1. Participants with either:

               1. Metastatic pancreatic cancer with tumor progression after one prior standard
                  chemotherapy; or,

               2. Metastatic gastric or gastroesophageal junction cancer with tumor progression
                  after one prior standard chemotherapy; or,

               3. Hormone-refractory prostate cancer with tumor progression following treatment
                  with a taxane-containing regimen and at least one androgen synthesis inhibitor.

          2. Tumor with positive PSCA expression as determined by central testing.

          3. Participant has a radiographically measurable tumor.

          4. Age ≥18 years

          5. Participant has a life expectancy >12 weeks and is able to carry out daily life
             activities without difficulty (Eastern Cooperative Oncology Group performance status 0
             or 1).

          6. Participant has adequate venous access for apheresis or agree to use of a central line
             for apheresis collection

          7. Participant does not have significant side effects from previous anticancer treatment.

          8. Participant has adequate organ and blood cell counts.

          9. Sexually active participants must use medically acceptable methods of contraception
             for at least 1 year after study treatment.

        Exclusion Criteria:

          1. Pancreatic cancer with islet cell neoplasms or symptomatic coagulopathy.

          2. Gastric/GEJ with:

               1. Abnormal kidney function

               2. Non-healing wound, peptic ulcer, or bone fracture within 4 weeks of study
                  treatment

               3. History of gastric perforation and/or fistula within 6 months of study treatment

               4. Bowel obstruction, history or presence of other inflammatory enteropathy
                  including Crohn's disease, ulcerative colitis, or chronic diarrhea

               5. Chronic treatment with non-steroidal anti-inflammatory agents or anti-platelet
                  agents

               6. Significant bleeding disorder

               7. Symptomatic coagulopathy

          3. Prostate cancer with unstable bone lesions or symptomatic coagulopathy.

          4. Participant has a history of major surgery or treatment with other cancer therapy
             within 2-4 weeks before study treatment.

          5. Participant has an untreated brain tumor.

          6. Current severe, uncontrolled systemic disease including an ongoing, active infection
             requiring treatment with antibiotics within 2 weeks before study treatment.

          7. History of clinically significant heart problems.

          8. Participant is currently pregnant or breastfeeding.

          9. Participant requires chronic, systemic steroid therapy.

         10. Participant has an active, autoimmune disease that requires immunosuppressive therapy.
             Exceptions are vitiligo, type I diabetes, certain cases of hypothyroidism and
             psoriasis, or Hashimoto's thyroiditis on a stable dose of thyroid replacement therapy

         11. Participant is positive for Hepatitis B, Hepatitis C, HIV, syphilis, West Nile virus,
             or Chagas disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:35 days after BPX-601 treatment
Safety Issue:
Description:Incidence of dose limiting toxicity

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bellicum Pharmaceuticals

Trial Keywords

  • prostate stem cell antigen
  • BPX-601
  • AP1903
  • CAR T
  • PSCA-CAR
  • Hormone-refractory prostate cancer
  • rimiducid
  • gastric cancer
  • gastroesophageal junction cancer
  • pancreatic cancer

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