RAPA-201 Therapy of Solid Tumors

NCT05144698 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RAPA-201-STP-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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. 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. 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. 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.

Conditions

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

Keywords

Refractory to Checkpoint Therapy; PD-1; PD-L1; Adoptive T cell therapy; Regenerative Medicine

Outcome Measures

Primary Outcomes (1)

• Determine the rate of Treatment Emergent Adverse Events of RAPA-201 using host conditioning of Carboplatin plus Paclitaxel

  To determine the safety of RAPA-201 cell therapy when used in combination with a carboplatin plus paclitaxel (CP) standard-of-care chemotherapy regimen and in combination with anti-PD1 maintenance therapy. Specifically, the treatment will be determined to be safe if the following parameters are met: (Metric #1) using the metric of "grade 4/grade 5 toxicity toxicity attributable to the RAPA-201 cell therapy": for positive determination of safety, this metric must occur in 1 or fewer patients out of the initial 10 patients.

  Completion of RAPA-201 Therapy plus combination anti-PD1 maintenance therapy; occurs on average at 18-months after treatment initiation

Secondary Outcomes (3)

• Overall Response Rate

  One (1) year after the last dose of RAPA-201 cells.

• Progression Free Survival (PFS) and Overall Survival (OS)

  One (1) year after the last dose of RAPA-201 cells.

• Quality of Life (QOL)

  One (1) year after the last dose of RAPA-201 cells.

Other Outcomes (1)

• T Cell Immune Reconstitution

  One (1) year after study start.

Study Arms (1)

Administration of RAPA-201 cells

EXPERIMENTAL

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)

Biological: RAPA-201 Rapamycin Resistant T Cells; Drug: Chemotherapy Prior to RAPA-201 Therapy; Drug: Pembrolizumab (PD-1 Blocking Antibody)

Interventions

RAPA-201 Rapamycin Resistant T Cells BIOLOGICAL

Autologous Rapamycin-Resistant Th1/Tc1 Cells

Also known as: RAPA-201 cells

Administration of RAPA-201 cells

Chemotherapy Prior to RAPA-201 Therapy DRUG

Outpatient Carboplatin + Paclitaxel Regimen (CP Regimen)

Administration of RAPA-201 cells

Pembrolizumab (PD-1 Blocking Antibody) DRUG

Drug Therapy After RAPA-201 Therapy

Administration of RAPA-201 cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Advanced metastatic, recurrent, and unresectable solid tumor that has relapsed after ≥ one prior line of therapy.
• Subject must have received prior therapy with disease-specific regimens that have been established to convey a clinical benefit. Alternatively, subject must have been offered such regimens and provided written documentation of refusal to receive such regimens.
• Subject with solid tumors with genetic alterations and mutations (including but not limited to BRAF, BRCA, EGFR mutations, and ALK translocations) must have either received targeted therapy for such conditions or provided written documentation of refusal to receive such regimens.
• Exposure to an anti-PD-(L)1 monoclonal antibody therapeutic in the most recent line of prior therapy.
• Documented refractory status to the most recent regimen, which must include an anti-PD-(L)1 monoclonal antibody, as defined by lack of response after at least two cycles of therapy or relapse within 12-months of initiation of anti-PD-(L)1-containing therapy.
• Solid tumor disease types that are eligible for enrollment consist of:
• head and neck cancer (squamous cell carcinoma of oral cavity, larynx, nasopharynx, and other sites);
• malignant melanoma;
• small cell carcinoma, thoracic and extra-thoracic; and,
• non-small cell lung cancer.
• Presence of measurable disease to permit monitoring by RECISTv1.1 Criteria.
• Must have a potential source of autologous T cells potentially sufficient to manufacture RAPA-201 cells, as defined by a circulating absolute lymphocyte count (ALC) of ≥ 300 cells/μL.
• Patients must be ≥ two weeks from last solid tumor cancer chemotherapy, major surgery, radiation therapy and/or participation in investigational trials.

You may not qualify if:

• Other active malignancy (except non-melanoma skin cancer).
• Life expectancy \< 4 months.
• Seropositivity for HIV, hepatitis B, or hepatitis C, unless such conditions are in stable condition using adequate treatment.
• Uncontrolled hypertension.
• History of cerebrovascular accident within 6 months of enrollment.
• Myocardial infarction within 6 months prior to enrollment.
• NYHA class III/IV congestive heart failure.
• Uncontrolled angina/ischemic heart disease.
• Cancer metastasis to the central nervous system, unless such metastasis has been adequately treated.
• Pregnant or breastfeeding patients.
• Patients of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.
• Patients may be excluded at the discretion of the PI or if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk.

Sponsors & Collaborators

• Rapa Therapeutics LLC: lead

Study Sites (1)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Melanoma; Esophageal Squamous Cell Carcinoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Daniel Fowler, M.D.

  Rapa Therapeutics LLC

  STUDY DIRECTOR

Central Study Contacts

Daniel Fowler, M.D.

CONTACT

(301) 518-3104; dan@rapatherapeutics.com

Jennifer Sunga - Regulatory Affairs Associate

CONTACT

(571) 277-4916; jsunga@rapatherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Non-randomized, open label, multi-site, phase I/II trial

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: December 3, 2021
• Study Start: August 1, 2021
• Primary Completion: January 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)