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

Phase 1

Active, not recruiting

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

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.

Recruitment & Eligibility

Inclusion Criteria

Male or female subjects aged 18-80 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

Arm && Interventions

Group	Intervention	Description
SC291 Plus Chemotherapy Regimen	SC291	A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment with SC291

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Area under the concentration time curve (AUC) in peripheral blood
Evaluate host immunogenicity to SC291	24 months	Incidence of anti-CD19-directed CAR antibodies

Locations (10): City of Hope
🇺🇸
Duarte, California, United States
Stanford Cancer Institute
🇺🇸
Palo Alto, California, United States
Northside Hospital
🇺🇸
Atlanta, Georgia, United States
University of Kansas Medical Center
🇺🇸
Fairway, Kansas, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
Peter MacCallum Cancer Centre
🇦🇺
Melbourne, Victoria, Australia
Linear Clinical Research Ltd
🇦🇺
Nedlands, Western Australia, Australia