AB013. A pivotal phase 2 trial to compare PRTH-101, a monoclonal antibody targeting discoidin domain receptor 1 (DDR1), in combination with an immune checkpoint inhibitor (ICI) and ICI alone, for the treatment of recurrent or metastatic thymic epithelial carcinoma (TEC)
Clinical Trial in Progress (Study Protocol)

AB013. A pivotal phase 2 trial to compare PRTH-101, a monoclonal antibody targeting discoidin domain receptor 1 (DDR1), in combination with an immune checkpoint inhibitor (ICI) and ICI alone, for the treatment of recurrent or metastatic thymic epithelial carcinoma (TEC)

Joseph Paul Eder, Susan Macdonald, Irena Webster

Incendia Therapeutics, Cambridge, MA, USA

Correspondence to: Susan Grace Macdonald, PhD. Incendia Therapeutics, One Canal Park, Suite 200, Cambridge, MA 02141, USA. Email: sue.macdonald@incendiatx.com.

Background: PRTH-101 is a humanized monoclonal that blocks the interaction of collagen with the extracellular domain of discoidin domain receptor 1 (DDR1) and has been studied in a phase 1, all-comers clinical trial (NCT05753722). In that trial, patients with thymic carcinoma or thymoma were treated with PRTH-101 alone or in combination with pembrolizumab. We observed stable disease, one confirmed partial response, multiple minor RECIST improvements, and improved quality of life in patients across all tumor types. Based on these results, a world-wide registrational trial is planned, to be initiated in 2026, enrolling patients ≥12 years old with recurrent or metastatic thymic epithelial carcinoma (TEC). The objective of this article is to describe the planned phase 2 pivotal study.

Methods: This open-label trial is a two-cohort trial. Cohort 1 will enroll ~45 immune checkpoint inhibitor (ICI)-refractory patients for treatment with PRTH-101 plus pembrolizumab. The sample size provides 90% power with a one-sided alpha =0.05 to detect a difference between the hypothesized null median progression-free survival (mPFS) of 3 months and target mPFS of 6 months. Cohort 2 will enroll ~84 ICI-naive patients randomized 1:1 to a pembrolizumab alone group and a PRTH-101 plus pembrolizumab group. The sample size provides 80% power with a one-sided alpha =0.05 and hazard ratio of 0.05, assuming an interim analysis for futility and efficacy when half of the expected 73 progression-free survival (PFS) events have occurred. Primary objectives are PFS, safety, and tolerability. Secondary objectives will assess pharmacokinetics and anti-drug antibodies. Exploratory endpoints include tumor evaluation by magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), analyses of efficacy by expression of programmed death-ligand 1 (PD-L1) and DDR1, and assessment of health-related quality-of-life. There will be two planned data cut offs (DCOs) for the primary endpoint of PFS: for futility (DCO1), to occur when approximately 30% of PFS events have been observed in cohort 2; and a final analysis (DCO2) to occur when approximately 73 PFS events in Cohort 2 have been observed.

Discussion: The design allows for comparison of the efficacy of PRTH-101 plus pembrolizumab and pembrolizumab alone in ICI-naïve patients, and for evaluation of PRTH-101 benefit when added with pembrolizumab in patients previously refractory to immune checkpoint inhibitors. Trial sub-analyses may identify patients most likely to benefit from treatment with PRTH-101 alone or in combination with pembrolizumab.

Trial Registration: Pending.

Keywords: PRTH-101; discoidin domain receptor 1 (DDR1); programmed death-ligand 1 (PD-L1); pivotal; pembrolizumab

Acknowledgments

None.

Footnote

Funding: This study was supported by Incendia Therapeutics.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-25-ab013/coif). S.M., J.P.E. and I.W. are the employees of Incendia Therapeutics and received support for attending meetings and stock options from Incendia Therapeutics. J.P.E. and S.M. may be named as an inventor on a methods-of-use patent for PRTH-101. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study will be conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Relevant institutional ethics approval and informed consent has not been obtained as the trial registration is still pending.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

doi: 10.21037/med-25-ab013
Cite this abstract as: Eder JP, Macdonald S, Webster I. AB013. A pivotal phase 2 trial to compare PRTH-101, a monoclonal antibody targeting discoidin domain receptor 1 (DDR1), in combination with an immune checkpoint inhibitor (ICI) and ICI alone, for the treatment of recurrent or metastatic thymic epithelial carcinoma (TEC). Mediastinum 2025;9:AB013.

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