P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM)

• ClinicalTrials.gov Identifier: NCT03288493
• Recruitment Status: Terminated
• First Posted: September 20, 2017
• Last Update Posted: May 24, 2022
• Sponsor: Poseida Therapeutics, Inc.
• Collaborator: California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): Poseida Therapeutics, Inc.

Study Description

Brief Summary:

Phase 1 of the study is comprised of an open-label, single ascending dose (SAD), multiple cohort study; a multiple dose cycle administration cohort study; and a combination administration study of P-BCMA-101 autologous T stem cell memory (Tscm) CAR-T cells in patients with relapsed / refractory MM. Followed by a Phase 2, open-label, efficacy and safety study. Rimiducid may be administered as indicated.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Biological: P-BCMA-101 CAR-T cells; Drug: Rimiducid	Phase 1; Phase 2

Detailed Description:

Phase 1 follows a 3 + 3 design of dose-escalating cohorts. Phase 2 of the study is an open-label multi-center efficacy and safety study. After a patient enrolls, leukapheresis will be performed to obtain peripheral blood mononuclear cells which will be sent to a manufacturing site to produce P-BCMA-101 CAR-T cells. The cells will then be returned to the investigational site and, after a standard chemotherapy based conditioning regimen, will be administered to the patient across 1-3 infusions, with or without combination therapy. Treated patients will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 105 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1: open label, 3 + 3 design of dose-escalating cohorts Phase 2: open label, administered as a total dose
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label, Multicenter, Phase 1 Study to Assess the Safety of P BCMA-101 in Subjects With Relapsed / Refractory Multiple Myeloma (MM) Followed by a Phase 2 Assessment of Response and Safety (PRIME)
• Actual Study Start Date: September 20, 2017
• Actual Primary Completion Date: April 27, 2022
• Actual Study Completion Date: April 27, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1: P-BCMA-101 CAR-T cells; Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells. Rimiducid may be administered as indicated.	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.
Experimental: Phase 1 P-BCMA-101 CAR-T cells (Cohort A); Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.
Experimental: Phase 1 P-BCMA-101 CAR-T cells (Cohort B); Single dose given across three intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.
Experimental: Phase 1 P-BCMA-101 CAR-T cells (Cohort C); Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.
Experimental: Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R); Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.
Experimental: Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP); Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before apheresis. Rimiducid may be administered as indicated.	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.
Experimental: Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT); Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.
Experimental: Phase 2: P-BCMA-101 CAR-T Cells; CAR-T cells administered via intravenous infusion as a total dose	Biological: P-BCMA-101 CAR-T cells; P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.; Drug: Rimiducid; Rimiducid (safety switch activator) may be administered as indicated.

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Assess the Safety of P-BCMA-101 [ Time Frame: Baseline through Day 28 ]
   Incidence and severity of treatment-emergent adverse events
2. Phase 1: Maximum tolerated dose of P-BCMA-101 [ Time Frame: Baseline through Day 28 ]
   Rate of dose limiting toxicities (DLT)
3. Phase 2: Assess the safety of P-BCMA-101 [ Time Frame: Baseline through 24 months ]
   Incidence and severity of treatment-emergent adverse events
4. Phase 2: Assess the efficacy of P-BCMA-101 (ORR) [ Time Frame: Baseline through 24 months ]

   According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

   Overall Response Rate (ORR)-Percentage of patients with complete response (CR), very good partial response (VGPR), or partial response (PR).

5. Phase 2: Assess the efficacy of P-BCMA-101 (DOR) [ Time Frame: Baseline through 24 months ]

   According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

   Duration of Response (DOR)-Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.

Secondary Outcome Measures :

1. Phase 1:Assess the safety of P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
   Incidence and severity of treatment-emergent adverse events
2. Phase 1:Assess the feasibility P-BCMA-101 [ Time Frame: Baseline through Month 24 ]
   Ability to generate protocol-proscribed doses of P-BCMA-101.
3. Phase 1: Anti-myeloma effect of P-BCMA-101 (ORR) [ Time Frame: Baseline through Month 24 ]

   According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

   Overall Response Rate (ORR)-Percentage of patients with complete response (CR), very good partial response (VGPR), or partial response (PR).

4. Phase 1: Anti-myeloma effect of P-BCMA-101 (TTR) [ Time Frame: Baseline through Month 24 ]

   According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

   Time to Response (TTR)-Time to complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.

5. Phase 1: Anti-myeloma effect of P-BCMA-101 (DOR) [ Time Frame: Baseline through Month 24 ]

   According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

   Duration of Response (DOR)-Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.

6. Phase 1: Anti-myeloma effect of P-BCMA-101 (PFS) [ Time Frame: Baseline through Month 24 ]

   According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

   Progression Free Survival (PFS)-Time from P-BCMA-101 treatment to progressive disease.

7. Phase 1: Anti-myeloma effect of P-BCMA-101 (OS) [ Time Frame: Baseline through Month 24 ]

   According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

   Overall Survival (OS)-Duration of survival from time of treatment with P-BCMA-101.

8. Phase 1: The effect of cell dose to guide selection of doses for further assessment in Phase 2/3 studies [ Time Frame: Baseline through Month 24 ]
   Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)
9. Phase 2: Incidence and severity of cytokine release syndrome (CRS) [ Time Frame: Baseline through Month 24 ]
   Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)
10. Phase 2: Evaluate Efficacy Endpoints (IL-6) [ Time Frame: Baseline through Month 24 ]
    Rate of IL-6 antagonist
11. Phase 2: Evaluate Efficacy Endpoints (C) [ Time Frame: Baseline through Month 24 ]
    Corticosteroid Use
12. Phase 2: Evaluate Efficacy Endpoints (R) [ Time Frame: Baseline through Month 24 ]
    Rimiducid Use
13. Phase 2: Evaluate Efficacy Endpoints (OS) [ Time Frame: Baseline through Month 24 ]

    According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

    Overall Survival (OS)-Duration of survival from time of treatment with P-BCMA-101.

14. Phase 2: Evaluate Efficacy Endpoints (PFS) [ Time Frame: Baseline through Month 24 ]

    According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

    Progression Free Survival (PFS)-Time from P-BCMA-101 treatment to progressive disease.

15. Phase 2: Evaluate Efficacy Endpoints (TTR) [ Time Frame: Baseline through Month 24 ]

    According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma:

    Time to Response (TTR)-Time to complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.

16. Phase 2: Evaluate Efficacy Endpoints (MRD) [ Time Frame: Baseline through Month 24 ]
    Minimum residual disease negative rate

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males or females, ≥18 years of age
• Must have a confirmed diagnosis of active MM
• Must have measurable MM
• Must have relapsed / refractory MM, having received treatment with proteasome inhibitor and IMiD [Phase 2: Must have relapsed / refractory MM, and refractory to last line of therapy, having received treatment with proteasome inhibitor, an IMiD, CD38 targeted therapy and undergone autologous stem cell transplant (ASCT) or not a candidate for ASCT.]
• Must have adequate hepatic, renal, cardiac and hematopoietic function

Exclusion Criteria:

• Is pregnant or lactating
• Has inadequate venous access and/or contraindications to leukapheresis
• Has active hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, amyloidosis, significant autoimmune, CNS or other malignant disease
• Has an active second malignancy (not disease-free for at least 5 years) in addition to MM, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma.
• Has active autoimmune disease
• Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy, etc.
• Has an active systemic infection
• Has hepatitis B or C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome.
• Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol
• Has receiving immunosuppressive or other contraindicated therapies within the excluded time frame from entry
• Has CNS metastases or symptomatic CNS involvement
• Has a history of having undergone allogeneic stem cell transplantation, or any other allogeneic or xenogeneic transplant, or has undergone autologous transplantation within 90 days.
• Unable to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation. (Cohorts R and RP only).
• History of thromboembolic disease within the past 6 months, regardless of anticoagulation (Cohorts R and RP only).

Contacts and Locations

Locations

United States, Arizona

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

United States, California

University of California Davis

Davis, California, United States, 95618

University of California San Diego

San Diego, California, United States, 92093

University of California San Francisco

San Francisco, California, United States, 94143

United States, Colorado

Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

United States, Kansas

University of Kansas Cancer Center

Westwood, Kansas, United States, 66205

United States, Maryland

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201

Johns Hopkins University

Baltimore, Maryland, United States, 21231

United States, Michigan

Wayne State - Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, New Jersey

John Theurer Cancer Center

Hackensack, New Jersey, United States, 07601

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, United States, 37203

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Washington

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Poseida Therapeutics, Inc.

California Institute for Regenerative Medicine (CIRM)

Investigators

• Study Director: Rajesh Belani, M.D.; Sponsor Executive Medical Director

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.

• Responsible Party: Poseida Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03288493
• Other Study ID Numbers: P-BCMA-101-001
• First Posted: September 20, 2017
• Last Update Posted: May 24, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Poseida Therapeutics, Inc.:

CAR-T cells

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases