RAPA-201 / Rapa Therap - LARVOL DELTA

RAPA-201 T Cell Therapy for Relapsed, Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: Rapa Therapeutics LLC | Recruiting ➔ Completed | N=27 ➔ 15

Enrollment change • Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

Phase 2b of RAPA-201 Cell Therapy in Post-PD-(L)-1 Melanoma (clinicaltrials.gov) - P2 | N=65 | Not yet recruiting | Sponsor: Rapa Therapeutics LLC | Initiation date: Mar 2025 ➔ Nov 2025

Trial initiation date • Melanoma • Oncology • Solid Tumor

RAPA-201 Therapy of Solid Tumors (clinicaltrials.gov) - P1/2 | N=37 | Recruiting | Sponsor: Rapa Therapeutics LLC | N=22 ➔ 37

Enrollment change • Breast Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Head and Neck Cancer • Laryngeal Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • BRCA • EGFR

Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma. (PubMed, J Immunother Cancer) - P2 | "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."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD73 • IFNA1 • LAIR1 • PD-1

Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma (J Immunother Cancer) - P2 | N=27 | NCT04176380 | Sponsor: Rapa Therapeutics LLC | "From December 2020 to December 2022, 14 patients with RRMM received a median of three RAPA-201 infusions (median dose, 80×106 cells). RAPA-201 drug products (DPs) were: polyclonal; enriched for TCM cells; reduced for immune checkpoint expression, including PD1, CD73, and LAIR1; and preferentially secreted Th1 cytokines. The median chemotherapy dose administered per cycle was 1,817 mg total for cyclophosphamide (range, 1,100–2,200) and 2.35 mg/M2 for pentostatin (range, 0–16). Nine of 14 patients (64%) achieved disease remission, with eight partial responses and one stringent complete response. Median progression-free survival was 6.0 months (range, 2.1 to>16.8 months)."

P2 data • Multiple Myeloma

RAPA-201 Therapy of Solid Tumors (clinicaltrials.gov) - P1/2 | N=22 | Recruiting | Sponsor: 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 • Bladder Cancer • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Laryngeal Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ALK • BRCA • EGFR

Phase 2b of RAPA-201 Cell Therapy in Post-PD-(L)-1 Melanoma (clinicaltrials.gov) - P2 | N=65 | Not yet recruiting | Sponsor: Rapa Therapeutics LLC

New P2 trial • Melanoma • Oncology • Solid Tumor

Ex vivo chemotherapy resistance of metabolically reprogrammed autologous Th1/Tc1 cells (RAPA-201): Towards the clinical translation of immune-sparing host conditioning (SITC 2023) - P1/2 | "Methods RAPA-201 were manufactured using one-week culture in temsirolimus- and IFN-α-containing media and tested for sensitivity to chemotherapy inhibition (temsirolimus, TEM; etoposide, VP-16; paclitaxel, PTX; carboplatin, CBCCA; and topotecan, TOPO; see table 1/figure 1: concentrations and exposure intervals). It is important to harness RAPA-201 chemotherapy resistance for clinical translation, as we have now successfully achieved through use of CBCCA/PTX immune-sparing conditioning to safely facilitate RAPA-201 regression of post-PD-(L)1 solid tumors. Finally, given RAPA-201 resistance to topotecan, which is in the topoisomerase I drug class commonly utilized as payload for antibody-drug-conjugates (ADC), it will be important to clinically translate combination therapy involving RAPA-201 and ADC agents."

Preclinical • Gastrointestinal Cancer • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Pancreatic Cancer • Solid Tumor • ABCB1 • IFNA1 • TOP1

Metabolically reprogrammed autologous Th1/Tc1 cell therapy (RAPA-201) yields promising safety and efficacy in post-PD-(L)1 solid tumor patients without lymphodepleting host conditioning (SITC 2023) - "2 RAPA-201 is also resistant to chemotherapy, including carboplatin (CBCCA), paclitaxel (PTX), and topotecan (Park JH et al, separate abstract submitted to SITC 2023)...Autologous RAPA-201 were manufactured using one-week culture in temsirolimus- and IFN-α-containing media (cryopreserved, 80–400 x 106 cells)...And, the remarkable RAPA-201 response rate (overall, 50%) for end-stage malignancy likely emanates from an ability of functionally-optimized T cells to target tumors in the context of disease-specific, immune-sparing conditioning. Ongoing efforts seek to characterize RAPA-201 mechanism of action, breakout clinical trial efforts in responsive tumor types (melanoma, SCLC), and continue evaluation of RAPA-201 in potentially sensitive tumor types (NSCLC, head and neck, gastric, bladder, triple-negative breast, and renal cell)."

Clinical • Hematological Malignancies • Lung Cancer • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • IFNA1

RAPA-201 Therapy of Solid Tumors (clinicaltrials.gov) - P1/2 | N=22 | Recruiting | Sponsor: 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 • Bladder Cancer • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Laryngeal Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ALK • BRCA • EGFR

Metabolically Reprogrammed Polyclonal Autologous Rapa-201 Cell Therapy Yields a Promising Safety and Efficacy Profile in Relapsed and Refractory Multiple Myeloma (RRMM) (ASH 2021) - P2 | "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..."

Clinical • IO biomarker • Febrile Neutropenia • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Nephrology • Oncology • Renal Disease • Transplantation • CCR7 • CD4 • CD8 • IFNG • IL10 • IL13 • IL15 • IL2RA • IL4 • IL5 • IL7 • PD-1 • SELL • TNFA

RAPA-201 Therapy of Solid Tumors (clinicaltrials.gov) - P2; N=22; Recruiting; Sponsor: Rapa Therapeutics LLC

New P2 trial • Bladder Cancer • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Laryngeal Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • ALK • BRCA • EGFR

RAPA-201 T Cell Therapy for Relapsed, Refractory Multiple Myeloma (clinicaltrials.gov) - P2; N=27; Recruiting; Sponsor: Rapa Therapeutics LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology