PlatΤform: A multicenter, multi-arm, academic platform trial evaluating novel agents and combinations in relapsed or refractory peripheral T-cell lymphomas Free

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous and aggressive group of mature T- or NK-cell neoplasms, with poor prognosis and limited therapeutic advances compared to B-cell lymphomas. Drug development in PTCL is hindered by disease heterogeneity and rarity, lack of predictive biomarkers and relevant preclinical models, and limited industry investment. There is an urgent need for flexible trial designs that are biomarker- or histology-driven to identify active therapies and define optimal patient subsets for future registration strategies.

PlaTform (NCT07018752) is a French academic, multicenter, open-label, multi-arm phase 1/2 platform trial evaluating novel agents or combinations in relapsed/refractory (R/R) PTCL using a master protocol framework. Patients will be enrolled and randomly assigned across available sub-studies, unless specific contraindications apply. Sub-studies may be a phase 1, a phase 1/2 or a phase 2. A shared screening process and centralized pathology review enable harmonized inclusion and integrated translational analyses. In the phase 1 sub-studies, the number of patients will be adapted to the specific needs of each sub-study. Each phase 2 sub-study will include up to 31 evaluable patients. The primary endpoint of phase 1 is determination of maximum tolerated dose and recommended phase 2 dose based on Bayesian Optimal Interval (BOIN) or Bayesian Continual Monitoring with Reassessment (BCMR) design, while the primary endpoint of phase 2 is modified progression-free survival, which includes disease progression, relapse, unplanned lymphoma therapy, or death. Secondary endpoints include overall and complete response rates, duration of response, overall survival, and safety. Exploratory objectives include correlation of genomic and immunological features with outcome, including patient-derived xenograft generation and next-generation sequencing profiling.

Eligible patients are ≥18 years old, with histologically confirmed R/R PTCL (excluding cutaneous T-cell lymphoma, T-cell large granular lymphocytic leukemia, and T-lymphoblastic lymphoma), measurable disease per Lugano 2014 criteria, ECOG performance status 0–2 (or 3 if related to lymphoma), and adequate organ function. Fresh or archival tumor tissue is required for central review and biomarker analyses. Each sub-study has additional and specific inclusion and exclusion criteria.

Two sub-studies are currently open:

• GolcAza: evaluates the combination of golcadomide and oral azacitidine in R/R follicular helper T-cell lymphoma. This is a phase 1 study, aiming to recruit 18 patients. Patients will receive various doses of golcadomide in addition to oral azacitidine for a maximum of 2 years.

• Origina-Ly-T: evaluates roginolisib, a novel, oral, non-ATP competitive, allosteric small molecule inhibitor of PI3Kδ, in R/R PTCL. This is a phase 2 trial aiming to recruit 31 patients. Roginolisib will be administered as a monotherapy over 28-day cycles for 6 cycles. Patients demonstrating clinical benefit, as per investigator's assessment, may continue roginolisib for a maximum of 30 additional cycles (total 36 cycles).

First patient-in is expected in August 2025. A third sub-study will be initiated at the end of 2025. Additional arms will be added over time based on emerging clinical or translational data, and available agents.

PlaTform represents a novel academic initiative dedicated to R/R PTCL, designed to accelerate therapeutic innovation in this underserved population.

We wish to thank the patients and their families for their participation in the clinical trials, iOnctura for providing access to roginolisib, and Bristol-Myers Squibb for providing access to golcadomide and azacitidine.