Imviva Biotech Receives FDA IDE Authorization for clonoSEQ® Assay in TENACITY-01 Clinical Trial

FDA Authorizes clonoSEQ Assay for Imviva's TENACITY-01 Trial

Imviva Biotech announced that the U.S. FDA granted Investigational Device Exemption (IDE) authorization for Adaptive Biotechnologies’ clonoSEQ® assay for use in its TENACITY-01 clinical trial (NCT07070219). This trial evaluates CTD402, Imviva’s allogeneic anti-CD7 CAR-T cell therapy, for relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) and MRD-positive T-ALL/LBL. The highly sensitive next-generation sequencing-based clonoSEQ assay will identify eligible patients with MRD levels of 0.1% or higher for enrollment and precisely evaluate post-treatment minimal residual disease to support exploratory analyses.

• The FDA's IDE authorization is a crucial step for the TENACITY-01 trial, enabling the integration of clonoSEQ for highly sensitive MRD assessment. This authorization signifies the assay's capability for use in a regulated clinical program where results can inform patient management and accelerate clinical decision-making for CTD402.
• The clonoSEQ assay will serve two key functions: identifying patients with T-ALL/LBL who have MRD levels of 0.1% or higher for enrollment eligibility, and accurately detecting and quantifying MRD in post-treatment bone marrow samples to support comprehensive exploratory analyses of CTD402's efficacy.
• The TENACITY-01 trial investigates CTD402, an investigational allogeneic anti-CD7 CAR-T cell therapy, in a patient population facing high relapse rates despite improved remission. CTD402 incorporates advanced cell engineering, including TCR and HLA class II knockout, and proprietary ANSWER™ inhibitory ligands, aiming to provide an 'off-the-shelf' solution with immediate availability.

Addressing High Relapse Rates in T-ALL/LBL

Despite advances in frontline chemotherapy, T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) remains a high-risk disease with a prognosis inferior to B-precursor ALL, driven by frequent relapse, chemotherapy resistance, and a paucity of actionable molecular targets. Current regimens achieve five-year event-free survival rates of 80–90%; however, approximately 20% of patients experience relapse, at which point prognosis becomes dismal. Addressing these gaps requires a deeper understanding of molecular drivers and the development of targeted therapeutic strategies.

• Limited molecular stratification: Unlike B-precursor ALL, T-ALL lacks well-characterized prognostic cytogenetic or molecular abnormalities to guide therapy selection or support a robust targeted treatment framework, impeding personalized treatment approaches.

• Chemotherapy resistance and refractory relapse: Drug resistance and refractory relapses represent the most critical clinical challenges in T-ALL, with primary refractory or relapsed T-ALL and mixed phenotype myeloid/T-cell acute leukemia carrying particularly dismal prognoses. Nelarabine-based regimens remain the standard of care at relapse, underscoring the limited evolution of salvage options.

• Absence of effective targeted immunotherapy: Effective targeted immunotherapies are largely lacking for T-ALL. CAR-T cell therapy is complicated by shared antigen expression between malignant and healthy T cells, resulting in CAR-T cell fratricide, T-cell aplasia, and risk of blast contamination during manufacturing.

• Resistance mediated by PTEN loss and PI3K-AKT-mTOR activation: Loss of PTEN — through mutation or posttranslational inactivation — is common in primary T-ALL, driving chronic PI3K-AKT-mTOR1 activation, γ-secretase inhibitor (GSI) resistance, and suppression of p53-mediated apoptosis, collectively undermining multiple therapeutic strategies.

• JAK3 mutation conferring ruxolitinib resistance: JAK3 mutations function independently of JAK1 and IL2RG, conferring high oncogenic potential and resistance to ruxolitinib, meaning standard JAK inhibitor strategies may be ineffective in this molecular subgroup.

• Urgent need for molecularly informed, personalized approaches: There is a critical unmet need to characterize the molecular alterations driving leukemogenesis at relapse in order to implement precision therapies with higher efficacy and reduced adverse effect profiles.

TENACITY-01: Evaluating CTD402 in T-ALL/LBL

Several clinical trials have investigated novel therapeutic strategies in T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LBL), spanning newly diagnosed and relapsed/refractory settings across pediatric and adult populations. The studies below represent a cross-section of phase 2 and phase 3 designs evaluating chemotherapy combinations, targeted agents, and immunotherapy backbones.