RAPA-201 Therapy of Solid Tumors

Part of paid clinical trials in Hackensack, New Jersey.

Sponsor
Rapa Therapeutics LLC
Study ID
NCT05144698
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Esophageal Squamous Cell Carcinoma
  • Head and Neck Cancer
  • Malignant Melanoma
  • Small Cell and Non-small Cell Lung Cancer
  • Solid Tumor
  • Squamous Cell Carcinoma of Larynx
  • Squamous Cell Carcinoma of Nasopharynx
  • Squamous Cell Carcinoma of Oral Cavity
  • Squamous Cell Carcinoma of Other Specified Sites of Skin

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • RAPA-201 Rapamycin Resistant T Cells — BIOLOGICAL
    Autologous Rapamycin-Resistant Th1/Tc1 Cells
  • Chemotherapy Prior to RAPA-201 Therapy — DRUG
    Outpatient Carboplatin + Paclitaxel Regimen (CP Regimen)
  • Pembrolizumab (PD-1 Blocking Antibody) — DRUG
    Drug Therapy After RAPA-201 Therapy

Study Details

The therapy of solid tumors has been revolutionized by immune therapy, in particular, approaches that activate immune T cells in a polyclonal manner through blockade of checkpoint pathways such as PD-1 by administration of monoclonal antibodies. In this study, the investigators will evaluate the adoptive transfer of RAPA-201 cells, which are checkpoint-deficient polyclonal T cells that represent an analogous yet distinct immune therapy treatment platform for solid tumors. The administration of polyclonal, metabolically-fit RAPA-201 cells is a novel adoptive T cell therapy approach that is suitable for regenerative medicine efforts. RAPA-201 is a novel immunotherapy product consisting of reprogrammed autologous CD4+ and CD8+ T cells of Th1/Tc1 cytokine phenotype. RAPA-201, which have acquired resistance to the mTOR inhibitor temsirolimus, are manufactured ex vivo from peripheral blood mononuclear cells collected from solid tumor patients using a steady-state apheresis. The novel RAPA-201 manufacturing platform, which incorporates both an mTOR inhibitor (temsirolimus) and an anti-cancer Th1/Tc1 polarizing agent (IFN-alpha) generates polyclonal T cells with five key characteristics: 1. Th1/Tc1: polarization to anti-cancer Th1 and Tc1 subsets, with commensurate down-regulation of immune suppressive Th2 and regulatory T (TREG) subsets; 2. T Central Memory: expression of a T central memory (TCM) phenotype, which promotes T cell engraftment and persistence for prolonged anti-tumor effects; 3. Rapamycin-Resistance: acquisition of rapamycin-resistance, which translates into a multi-faceted anti-apoptotic phenotype that improves T cell fitness in the stringent conditions of the tumor microenvironment; 4. T Cell Quiescence: reduced T cell activation, as evidence by reduced expression of the IL-2 receptor CD25, which reduces T cell-mediated cytokine toxicities such as cytokine-release syndrome (CRS) that limit other forms of T cell therapy; and 5. Reduced Checkpoints: multiple checkpoint inhibitory receptors are markedly reduced on RAPA-201 cells (including but not limited to PD-1, CTLA4, TIM-3, LAG3, and LAIR1), which increases T cell immunity in the checkpoint-replete, immune suppressive tumor microenvironment. This is a non-randomized, open label, multi-site, phase I/II trial of outpatient RAPA-201 immune T cell therapy in patients with advanced metastatic, recurrent, and unresectable solid tumors that have recurred or relapsed after prior immune therapy. Patients must have tumor relapse after at least one prior line of therapy and must have refractory status to the most recent regimen, which must include an anti-PD-(L)1 monoclonal antibody. Furthermore, accrual focuses upon solid tumor disease types potentially amenable to standard-of-care salvage chemotherapy consisting of the carboplatin + paclitaxel (CP) regimen that will be utilized for host conditioning prior to RAPA-201 therapy. Importantly, carboplatin and paclitaxel are "immunogenic" chemotherapy agents whereby the resultant cancer cell death mechanism is favorable for generation of anti-tumor immune T cell responses. Thus, the CP regimen that this protocol incorporates is intended to directly control tumor progression and indirectly promote anti-tumor T cell immunity. Protocol therapy consists of six cycles of standard-of-care chemotherapy (carboplatin + paclitaxel (CP) regimen) administered in the outpatient setting every 28 days (chemotherapy administered on cycles day 1, 8, and 15). RAPA-201 cells will be administered at a target flat dose of 400 X 10\^6 cells per infusion on day 3 of cycles 2 through 6. In the original protocol design, a sample size of up to 22 patients was selected to determine whether RAPA-201 therapy, when used in combination with the CP regimen, represents an active regimen in solid tumors that are resistant to anti-PD(L)-1 checkpoint inhibitor therapy, as defined by a response rate (≥ PR) consistent with a rate of 35%. The first stage of protocol accrual consisted of n=10 patients; to advance to the second protocol accrual stage (accrual of an additional n=12 patients), RAPA-201 therapy must result in a tumor response (≥ PR) in at least 2 out of the 10 initial patients. As described below in the detailed description, this original protocol implementation demonstrated that RAPA-201 represented an active treatment regimen for solid tumor patients, and as such, the protocol was expanded to evaluate the combination of RAPA-201 therapy followed by anti-PD1 maintenance therapy.

Key Dates

Start date
Aug 1, 2021
Status verified
May 2025
Primary completion
Jan 1, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
37 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Administration of RAPA-201 cells
    RAPA-201 cells will be administered at a target flat dose of 400 x 10\^6 cells per infusion. After RAPA-201 therapy, anti-PD1 maintenance therapy (pembrolizumab, 200 mg administered intravenously every 3 weeks for up to 12 months)

Primary Outcome Measure

Determine the rate of Treatment Emergent Adverse Events of RAPA-201 using host conditioning of Carboplatin plus Paclitaxel [ Time Frame: Completion of RAPA-201 Therapy plus combination anti-PD1 maintenance therapy; occurs on average at 18-months after treatment initiation ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Hackensack University Medical CenterHackensackNew Jersey07601
Oncology Clinical Research Referral Office
[email protected]
551-996-1777
Martin Gutierrez, M.D. (PRINCIPAL_INVESTIGATOR)

Find similar trials in Hackensack, NJ

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OncologyENTSkin cancerDermatology
By research site
Hackensack University Medical Center· Hackensack, NJ

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