^
    2ms
    Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma. (PubMed, J Immunother Cancer)
    Consistent with our hypothesis, ex vivo manufacturing using mTOR inhibition and IFN-α polarization consistently yielded a novel RAPA-201 DP that possessed a desirable phenotype relative to cytokine phenotype, memory status, and checkpoint expression. RAPA-201 recipients had preservation of T cell counts and Th1 cytokine secretion yet had increased T cell receptor clonality that associates with antitumor responses in the setting of monoclonal antibody checkpoint therapy. RAPA-201 therapy overcomes previous barriers to effective autologous polyclonal T-cell therapy, as it is feasible to manufacture, exquisitely safe to administer, and mediates remission in patients with RRMM.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-1 (Programmed cell death 1) • CD73 (5'-Nucleotidase Ecto) • IFNA1 (Interferon Alpha 1) • LAIR1 (Leukocyte Associated Immunoglobulin Like Receptor 1)
    |
    cyclophosphamide • sirolimus • fludarabine IV • pentostatin • RAPA-201
    2ms
    RAPA-201 Therapy of Solid Tumors (clinicaltrials.gov)
    P1/2, N=22, Recruiting, Rapa Therapeutics LLC | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jan 2024 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • BRCA (Breast cancer early onset)
    |
    EGFR mutation • ALK translocation • BRCA mutation
    |
    carboplatin • paclitaxel • Torisel (temsirolimus) • sirolimus • RAPA-201
    4ms
    Phase 2b of RAPA-201 Cell Therapy in Post-PD-(L)-1 Melanoma (clinicaltrials.gov)
    P2, N=65, Not yet recruiting, Rapa Therapeutics LLC
    New P2 trial
    |
    carboplatin • paclitaxel • Torisel (temsirolimus) • sirolimus • RAPA-201
    almost2years
    RAPA-201 Therapy of Solid Tumors (clinicaltrials.gov)
    P1/2, N=22, Recruiting, Rapa Therapeutics LLC | Phase classification: P2 --> P1/2 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Jan 2023 --> Jan 2024
    Phase classification • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • BRCA (Breast cancer early onset)
    |
    EGFR mutation • ALK translocation • BRCA mutation
    |
    carboplatin • paclitaxel • Torisel (temsirolimus) • sirolimus • RAPA-201
    over3years
    RAPA-201 Therapy of Solid Tumors (clinicaltrials.gov)
    P2, N=22, Recruiting, Rapa Therapeutics LLC
    New P2 trial
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • BRCA (Breast cancer early onset)
    |
    EGFR mutation • ALK translocation • BRCA mutation
    |
    paclitaxel • Torisel (temsirolimus) • sirolimus • RAPA-201
    over3years
    Metabolically Reprogrammed Polyclonal Autologous Rapa-201 Cell Therapy Yields a Promising Safety and Efficacy Profile in Relapsed and Refractory Multiple Myeloma (RRMM) (ASH 2021)
    In a first-generation trial using ex vivo rapamycin, polyclonal autologous Th1/Tc1 (RAPA-101) cells were safe and associated with delayed relapse when administered after hematopoietic cell transplantation in high-risk MM patients. Now, we are evaluating temsirolimus for manufacture of second-generation RAPA-201 cells...Bridging chemotherapy during manufacturing (Cycle 1) and host conditioning prior to RAPA-201 infusion consisted of the 14-day PC regimen [pentostatin (4 mg/m 2 IV; days 1, 4, 8, 12; dose adjusted/omitted with renal insufficiency); cyclophosphamide (100-200 mg PO, days 1-5 and days 8-12)]...RAPA-201 therapy represents a new paradigm that utilizes stringent mTOR inhibition to reprogram Th1/Tc1 cells for enhanced metabolic fitness and induction of in vivo T cell clonal expansion, thus providing an alternative to gene-modified targeted T cell therapy. With these promising safety and efficacy results, current RAPA-201 developmental efforts are directed towards completing protocol accrual in parallel with the design and implementation of next-generation clinical trials.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • IL10 (Interleukin 10) • CCR7 (Chemokine (C-C motif) receptor 7) • IL13 (Interleukin 13) • IL4 (Interleukin 4) • SELL (Selectin L)
    |
    CCR7 expresion
    |
    cyclophosphamide • Torisel (temsirolimus) • sirolimus • pentostatin • RAPA-201