Study Evaluating SC291 in Subjects With r/r B-cell Malignancies (ARDENT)

Sponsor

Sana Biotechnology (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05878184

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

SC291-101 is a Phase 1 study to evaluate SC291 safety and tolerability, anti-tumor activity, cellular kinetics, immunogenicity, and exploratory biomarkers.

Condition or Disease	Intervention/Treatment	Phase
Non Hodgkin Lymphoma Chronic Lymphocytic Leukemia	Drug: SC291	Phase 1

Detailed Description

This is an open-label, single arm, Phase 1, first-in-human (FIH) study to evaluate the safety and tolerability of SC291 administered intravenously (IV) following a standard lymphodepleting chemotherapy regimen of cyclophosphamide and fludarabine in subjects with NHL or CLL who have received two or more prior systemic treatments per standard of care (or after autologous stem cell transplant [ASCT] for NHL). This study will be conducted in 2 parts. Phase 1a: dose finding using a 3+3 design in subjects with NHL or CLL. Phase 1b: dose expansion to further evaluate safety and efficacy at the RP2D in subjects with LBCL and CLL.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

54 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study Evaluating SC291, a Hypoimmune, Allogeneic CD19-directed CAR T Cell Therapy, in Relapsed and/or Refractory B-cell Malignancies (ARDENT)

Actual Study Start Date :

May 2, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SC291 Plus Chemotherapy Regimen A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment with SC291	Drug: SC291 SC291 is an allogeneic CAR-T cell therapy Other Names: Cyclophosphamide Fludarabine

Arm

Intervention/Treatment

Experimental: SC291 Plus Chemotherapy Regimen

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment with SC291

Drug: SC291

SC291 is an allogeneic CAR-T cell therapy

Other Names:

Cyclophosphamide

Fludarabine

Outcome Measures

Primary Outcome Measures

Evaluate safety and tolerability of SC291 [24 months]
Safety and Tolerability: Proportion of subjects experiencing adverse events and dose-limiting toxicities

Secondary Outcome Measures

Evaluate preliminary anti-tumor activity of SC291 [24 months]
Preliminary anti-tumor activity: Proportion of subjects with an objective response (including partial response or complete response)
Evaluate cellular kinetics and persistence of SC291 [24 months]
Cellular kinetics-related parameters evaluated by CAR T cell copy number
Evaluate cellular kinetics and persistence of SC291 [24 months]
Cellular kinetics related peak (Cmax) in peripheral blood
Evaluate cellular kinetics and persistence of SC291 [24 months]
Area under the concentration time curve (AUC) in peripheral blood
Evaluate host immunogenicity to SC291 [24 months]
Incidence of anti-CD19-directed CAR antibodies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female subjects aged 18-75 years at the time of signing informed consent.
Diagnosis of NHL (WHO 2016 criteria) or CLL (iwCLL criteria), including:
Large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise -
specified (including DLBCL arising from indolent lymphoma), primary mediastinal large -- - B-cell lymphoma, high grade B-cell lymphoma, follicular lymphoma grade 3B
Follicular lymphoma (dose escalation only except for follicular lymphoma grade 3B)
Marginal zone lymphoma (dose escalation only)
Mantle cell lymphoma (dose escalation only)
CLL or SLL
Relapsed/refractory disease after at least 2 prior systemic regimens per standard of care or after autologous stem cell transplant
ECOG performance status of 0 or 1.
At least one measurable lesion per Lugano Classification (NHL); CLL subjects must meet iwCLL treatment criteria
Life expectancy ≥12 weeks

Exclusion Criteria:

Prior anti-CD19 therapy including CD19-directed CAR T treatment or other CD19-directed antibody or cell therapy (e.g., NK cell). (Part 2 dose expansion only - prior approved CD19-directed CAR T therapy required)
History of primary central nervous system (CNS) lymphoma or presence of CNS metastases
Systemic anticancer therapy (including platinum-based chemotherapies and I/O therapies) or radiotherapy within 14 days of SC291 (28 days for biologics)
Autologous HSCT within 6 weeks of treatment with SC291 (or allogeneic HSCT at any time).
Active autoimmune disease or any other diseases requiring immunosuppressive therapy or corticosteroid therapy (defined as >20 mg/day prednisone or equivalent).
History or presence of cardiac or CNS disorders as defined in the protocol