TRACON reports that TRC102, temozolomide combination fails Phase II glioblastoma trial

TRACON Pharmaceuticals on Monday presented findings at the Society for Neuro-Oncology (SNO) annual meeting, indicating that TRC102 (methoxyamine) plus temozolomide, which Merck & Co. markets as Temodar, did not meet the primary efficacy endpoint in a Phase II trial of patients with recurrent glioblastoma. According to TRACON, TRC102 is a small molecule inhibitor of the base excision repair (BER) pathway that causes resistance to temozolomide chemotherapy in preclinical tumour models.

The trial involved 19 patients with glioblastoma who received TRC102 and temozolomide at the time of recurrence following first-line therapy with temozolomide and radiation therapy. The primary endpoint was demonstrating objective responses as measured by Response Assessment in Neuro-Oncology criteria.

TRACON noted that two patients exhibited evidence of clinical benefit and met the secondary endpoint of progression-free survival (PFS) beyond six months. The company said "both patients, who demonstrated PFS for more than 11 months, remain alive over 30 months following treatment initiation with TRC102 and [temozolomide] for recurrent glioblastoma." TRACON also pointed out that "PFS of greater than 11 months was associated with N-methylpurine DNA glycosylase expression, a biomarker that initiates the BER pathway of resistance that is inhibited by TRC102."

CEO Charles Theuer remarked "we recognised that the primary endpoint of objective response in the Phase II trial of [temozolomide] and TRC102 represented a high efficacy hurdle, that of resensitising recurrent glioblastoma patients to [temozolomide] treatment." He added that TRACON "will continue to focus on identifying possible biomarkers that are prognostic of response to TRC102 in four ongoing clinical trials supported by the National Cancer Institute." 

Aside from recurrent glioblastoma, TRC102 is in early-stage testing in combination with temozolomide for use in relapsed solid tumours and lymphomas, as well as in combination with Eli Lilly's Alimta (pemetrexed) in advanced solid tumours or mesothelioma. The therapy is also being evaluated together with chemoradiation for potential use in non-squamous non-small-cell lung cancer.


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