Incendia Therapeutics presented promising Phase 1 clinical data for PRTH-101, a first-in-class discoidin domain receptor 1 (DDR1)-targeted antibody therapy, at the International Thymic Malignancy Interest Group Annual Meeting in Milan, Italy. The therapy demonstrated encouraging anti-tumor activity in patients with recurrent/metastatic thymic epithelial carcinoma (TEC), a rare cancer with limited treatment options.
Clinical Efficacy in Thymic Cancers
Among 18 TEC patients evaluated as of September 4, 2025, PRTH-101 achieved a median progression-free survival (mPFS) of 7.9 months, substantially exceeding literature reports of 4.2 months for this patient population. The therapy showed two confirmed partial responses across tumor types, with multiple patients experiencing minor RECIST improvements and quality of life benefits.
"PRTH-101 has shown encouraging anti-tumor activity in TEC patients, particularly in those with high DDR1 expression," said Wendye R. Robbins, M.D., president and CEO of Incendia Therapeutics. "Traditionally, elevated tumor DDR1 has been associated with worsened outcomes. These results support the potential of DDR1 inhibition to overcome immune exclusion and improve outcomes in difficult-to-treat cancers, especially those with no approved therapies such as recurrent/metastatic TEC."
Novel Mechanism of Action
PRTH-101 targets DDR1, a collagen binding protein and kinase present on epithelial cells that tumor cells co-opt to build impenetrable barriers around tumors. By blocking collagen binding to DDR1, the therapy disrupts tumor-associated collagen alignment to permit immune cell access into the tumor core. In preclinical experiments, PRTH-101 demonstrated both single agent anti-tumor activity and marked augmentation of checkpoint inhibitor function.
Susan Macdonald, Ph.D., SVP Nonclinical Development and Strategy at Incendia Therapeutics, explained: "By attacking the structural and biochemical underpinnings of the TME, PRTH-101 can enable host immune cells to penetrate the tumor core and allow immunotherapies to act on the tumor, offering a potentially transformative treatment for patients with TEC and other immune excluded and fibrotic tumors."
Phase 1 Trial Design and Results
The ongoing Phase 1 trial (NCT05753722) is evaluating PRTH-101 as monotherapy (Phase 1a), in combination with pembrolizumab (Phase 1b), and in tumor-specific expansion cohorts (Phase 1c). The multi-center, open-label study expects to enroll up to 270 patients with advanced or metastatic solid tumors.
Key findings include correlations between DDR1 expression and progression-free survival with PRTH-101 treatment, both as monotherapy and in combination with pembrolizumab. Tumor responses correlated with expression of respective targets for both PRTH-101 and pembrolizumab. Multiple patients achieved prolonged stable disease beyond published expectations.
Planned Phase 2 Registration Trial
Based on the Phase 1 results, Incendia plans to initiate a pivotal Phase 2 registrational trial in 2026 for patients aged 12 years and older with recurrent or metastatic TEC. The global, open-label, two-cohort trial will evaluate PRTH-101 in combination with pembrolizumab versus pembrolizumab alone in both immune checkpoint inhibitor-refractory and ICI-naïve patient populations.
Primary and secondary endpoints will include overall response rate, progression-free survival, and safety, with exploratory assessments of advanced tumor imaging, DDR1 and PD-L1 biomarker expression, and quality-of-life measures. The trial design has been discussed with the FDA.
Broader Therapeutic Potential
Currently, no approved drugs target DDR1, making PRTH-101 a potentially first-in-class therapy. Tumor types expressing high levels of DDR1-associated collagen barriers include thymic, colorectal, pancreatic, ovarian, glioma, and non-small cell lung cancers, suggesting broader therapeutic applications beyond thymic malignancies.
The Phase 1 trial continues to evaluate DDR1 and pathway-related proteins as predictive biomarkers for treatment response, which could help identify patients most likely to benefit from this novel therapeutic approach.
