TRACON Publishes Phase 2 Data for TRC102 in Recurrent Glioblastoma in Clinical Cancer Research

TRACON Pharmaceuticals, a clinical-stage biopharmaceutical company, has announced the release of Phase 2 clinical data for their DNA damage repair inhibitor, TRC102, in patients with glioblastoma. This data was published in the journal, Clinical Cancer Research. The study, titled "Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT," examines the effectiveness of TRC102 in combination with Temodar chemotherapy in patients who have experienced disease progression following initial treatments.

TRC102 was tested in 19 patients who had recurrent or progressive glioblastoma after undergoing surgical resection, Temodar, and external beam radiotherapy. The trial yielded promising results, particularly for two patients who exhibited extended survival—remaining progression-free for over 17 months and achieving an overall survival of over 32 months. RNA sequencing of these patients revealed significant activation of DNA damage response (DDR) pathways prior to the initiation of TRC102 and Temodar treatment, indicating a potential biomarker for predicting patient response to this therapeutic combination.

The study was led by Dr. Manmeet Alhuwalia, previously Chair of Neuro-Oncology at Cleveland Clinic and now Chief of Medical Oncology, Chief Scientific Officer, and Deputy Director at the Miami Cancer Institute. The authors concluded that the findings support the safety and feasibility of TRC102 combined with Temodar for recurrent glioblastoma patients and suggest further exploration of this combination in biomarker-enriched trials, especially for those with activated DDR pathways.

Dr. James Freddo, Chief Medical Officer of TRACON, highlighted the importance of these findings, stating that they provide a strong basis for further investigating TRC102 in combination with Temodar and radiotherapy for newly diagnosed patients with malignant glioma. This publication builds on previous data suggesting that patients with cancers exhibiting DDR pathway activation may be particularly responsive to TRC102.

TRC102 is also being investigated in a randomized Phase 2 clinical trial in combination with chemotherapy (pemetrexed, cisplatin, or carboplatin) and radiation therapy for stage III non-squamous non-small cell lung cancer. This trial, sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA), is expected to yield primary endpoint results in 2025. TRACON and the NCI have been collaborating to develop TRC102, with the NCI funding six Phase 1 or Phase 2 trials through the CRADA.

TRC102, also known as methoxyamine, is a small molecule inhibitor of the DNA base excision repair pathway, which is responsible for resistance to alkylating and antimetabolite chemotherapeutics. The drug received orphan drug designation from the US FDA for the treatment of malignant glioma in 2020.

Glioblastoma (GBM) is an aggressive type of malignant glioma originating from glial cells in the brain. It is the most invasive form of glial tumors, rapidly growing and spreading to nearby brain tissues. According to the National Cancer Institute, approximately 22,850 adults in the U.S. are diagnosed annually with brain and other nervous system cancers, with about 15,320 deaths. GBM accounts for 52% of all primary brain tumors, with an incidence rate of two to three per 100,000 adults annually in the U.S.

TRACON Pharmaceuticals employs a cost-efficient, CRO-independent product development platform to advance its pipeline of targeted cancer therapeutics and to collaborate with other life science companies. Their development strategy aims to bring innovative treatments to market efficiently, potentially offering new therapeutic options for patients with difficult-to-treat cancers like glioblastoma and lung cancer.