FDA grants Orphan Drug Designation to Tracon’s TRC102 in malignant glioma including GBM

TRC102 is being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA). TRC102 was evaluated in a Phase 2 trial in combination with Temodar chemotherapy in 19 patients with progressive or recurrent GBM who progressed following Temodar and external beam radiotherapy. Extended survival was observed in two patients for more than two years, both of whom demonstrated activation of the DNA base excision repair pathway and demonstrated hyperactivation of DNA damage response genes. TRC102 was also evaluated in combination with chemotherapy and external beam radiotherapy in a separate Phase 1 study of 15 patients with newly diagnosed non-squamous cell non-small cell lung cancer that resulted in a response by the Radiographic Evaluation Criteria in Solid Tumors (RECIST) in all patients, including three patients who had a complete response to treatment.

GBM (also called glioblastoma) is a fast-growing malignant glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults (12,630 men and 10,280 women) are diagnosed with brain and other nervous system cancer annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors.

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics.

Tracon to begin pivotal study of envafolimab

Charles Theuer, M.D., Ph.D., President and CEO of the company said “we are focused on advancing envafolimab as a single agent and in combination with Yervoy (ipilimumab) for the treatment of the sarcoma subtypes of UPS and MFS, both of which have been shown to be responsive to immune checkpoint inhibition treatment.” 

From the PR: 

The FDA determined the acceptability of the following key aspects of the proposed pivotal trial:

  • Multi-center, open-label, randomized, non-comparative, parallel cohort study.
  • Planned total enrollment of 160 patients, with 80 patients enrolled into cohort A of treatment with single agent envafolimab and 80 patients enrolled in cohort B with envafolimab and Yervoy.
  • Primary endpoint of objective response rate (ORR) with duration of response a key secondary endpoint.
  • Open-label format with blinded independent central review of endpoint data.
  • Eligible patients will have received one prior cancer therapy, but no prior checkpoint inhibitor therapy.

Envafolimab is a redacted, single-domain antibody against PD-L1 that is administered by subcutaneous injection without the need for an adjuvant. Envafolimab is currently dosing in Phase 1 trials in the U.S. and Japan and is being studied in China in a Phase 2 registration trial as a single agent in MSI-H tumor patients, and in a Phase 3 registration trial in combination with gemcitabine and oxaliplatin in biliary tract cancer. Subject to positive data from the MSI-H registrational trial, 3D Medicines, TRACON’s corporate partner for this program, plans to file a BLA in China for envafolimab in 2020 based on ORR in MSI-H patients. The filing would be based on the principle that the response rate required for approval in China is similar to the response rate seen with Keytruda and Opdivo in MSI-H patients from separate clinical trials per their U.S. product package inserts.