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Phase 3 TERZO Trial to Evaluate Duvelisib in Rare T-Cell Lymphoma Following Promising Phase 2 Results

• The upcoming TERZO trial will assess duvelisib against standard chemotherapy in patients with nodal T-cell lymphoma with follicular helper T phenotype, addressing a significant treatment gap in rare lymphomas.

• Phase 2 PRIMO study demonstrated promising results with duvelisib showing a 48% overall response rate and 33.3% complete response rate in relapsed/refractory PTCL patients.

• The TERZO trial aims to enroll 124 patients across EU and UK, with progression-free survival as the primary endpoint, potentially leading to regulatory approval if successful.

The landscape of T-cell lymphoma treatment may soon expand with the launch of the phase 3 TERZO trial (NCT06522737), investigating the PI3K-δ and PI3K-γ inhibitor duvelisib in patients with nodal T-cell lymphoma with follicular helper T phenotype, a rare subtype of peripheral T-cell lymphoma (PTCL).

Strong Preclinical Foundation and Previous Success

"The preclinical data supporting the mechanism of action and the potential efficacy of duvelisib in hematologic malignancies, including PTCL, are quite strong," states Christopher P. Fox, PhD, clinical professor at the University of Nottingham. The drug's potential builds on substantial evidence demonstrating anticancer activity through PI3K inhibition.

Promising Phase 2 PRIMO Results

The phase 2 PRIMO study provided compelling evidence for duvelisib's efficacy in relapsed/refractory PTCL. Among 123 patients, the treatment achieved:
  • 48% overall response rate
  • 33.3% complete response rate
  • Median duration of response of 7.89 months
  • Median overall survival of 12.35 months
The study employed an innovative dosing strategy, starting with 75mg twice daily for two cycles before reducing to 25mg twice daily, balancing efficacy with toxicity management.

Safety Profile and Management

The treatment demonstrated a manageable safety profile, with common adverse effects including increased liver enzymes and decreased neutrophil counts. While 97.6% of patients experienced treatment-emergent adverse effects, the frequency of severe immune-mediated toxicities was lower compared to other PI3K inhibitors.

TERZO Trial Design and Objectives

The TERZO trial represents a pivotal step forward, comparing duvelisib against investigator's choice of gemcitabine or bendamustine. Key features include:
  • 1:1 randomization
  • 124 planned participants across EU and UK
  • Primary endpoint: progression-free survival
  • Secondary endpoints including overall survival and quality of life
  • Scheduled to begin March 2025

Potential Impact on Treatment Landscape

"If [findings from] TERZO are positive and we see statistically significant superiority of duvelisib in terms of PFS, this would be a practice-changing study if the toxicity profile is deemed to be acceptable," Fox emphasizes. Success could mark a significant advancement in targeted therapy for this rare lymphoma subtype, potentially leading to regulatory approval.
The trial addresses a critical unmet need, as current treatment options for relapsed/refractory PTCL are limited, with brentuximab vedotin being the only approved agent for specific PTCL subtypes in the EU and UK.
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