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

• Sponsor: Poseida Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03288493
• Collaborator: California Institute for Regenerative Medicine (CIRM) (Other)
• Enrollment: 105
• Locations: 16
• Arms: 8
• Actual Duration (Months): 55.2
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.1

Study Details

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
• 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 dosePhase 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: Sep 20, 2017
• Actual Primary Completion Date: Apr 27, 2022
• Actual Study Completion Date: Apr 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 [Baseline through Day 28]

   Incidence and severity of treatment-emergent adverse events

2. Phase 1: Maximum tolerated dose of P-BCMA-101 [Baseline through Day 28]

   Rate of dose limiting toxicities (DLT)

3. Phase 2: Assess the safety of P-BCMA-101 [Baseline through 24 months]

   Incidence and severity of treatment-emergent adverse events

4. Phase 2: Assess the efficacy of P-BCMA-101 (ORR) [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) [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 [Baseline through Month 24]

   Incidence and severity of treatment-emergent adverse events

2. Phase 1:Assess the feasibility P-BCMA-101 [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) [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) [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) [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) [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) [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 [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) [Baseline through Month 24]

   Incidence and severity of CRS events graded using Lee criteria (Lee, 2014)

10. Phase 2: Evaluate Efficacy Endpoints (IL-6) [Baseline through Month 24]

    Rate of IL-6 antagonist

11. Phase 2: Evaluate Efficacy Endpoints (C) [Baseline through Month 24]

    Corticosteroid Use

12. Phase 2: Evaluate Efficacy Endpoints (R) [Baseline through Month 24]

    Rimiducid Use

13. Phase 2: Evaluate Efficacy Endpoints (OS) [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) [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) [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) [Baseline through Month 24]

    Minimum residual disease negative rate

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	University of California Davis	Davis	California	United States	95618
3	University of California San Diego	San Diego	California	United States	92093
4	University of California San Francisco	San Francisco	California	United States	94143
5	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
6	University of Chicago	Chicago	Illinois	United States	60637
7	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
8	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201
9	Johns Hopkins University	Baltimore	Maryland	United States	21231
10	Wayne State - Karmanos Cancer Institute	Detroit	Michigan	United States	48201
11	John Theurer Cancer Center	Hackensack	New Jersey	United States	07601
12	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
13	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee	United States	37203
14	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
15	MD Anderson Cancer Center	Houston	Texas	United States	77030
16	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Poseida Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03288493
• Other Study ID Numbers: P-BCMA-101-001
• First Posted: Sep 20, 2017
• Last Update Posted: May 24, 2022
• Last Verified: May 1, 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

Study Results

No Results Posted as of May 24, 2022