On October 9, 2016 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported final updated results from a Phase 1b clinical trial combining TRC105 with Inlyta (axitinib) in patients with advanced or metastatic renal cell carcinoma (RCC) (Press release, Tracon Pharmaceuticals, OCT 9, 2016, View Source;p=irol-newsArticle&ID=2210295 [SID:SID1234515718]). Data were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark. Preliminary data from this trial were previously presented at the Kidney Cancer Association meeting in November 2015 and the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium in February 2015.

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The open-label dose escalation and expansion Phase 1b study enrolled a total of 18 patients (17 of whom were evaluable for response) who had received at least one prior line of therapy with a VEGF receptor tyrosine kinase inhibitor (VEGFR TKI). The median number of prior therapies in the group was three with a range of one to six. All patients in the trial received a combination of TRC105 and Inlyta. Data are summarized in the table below.

Summary of Phase 1b Results for TRC105-Inlyta Combination
Patients ORR Stable
Disease Overall Disease
Control Median PFS Median PFS in Clear Cell
RCC Subset (n=12)
N = 17 29%
(5/17) 59%
(10/17) 88%
(15/17) 11.3 months 11.3 months
For comparison, the objective response rate (ORR) seen in the large subgroup of VEGFR TKI-refractory patients treated with Inlyta (n=194) in the Inlyta AXIS Phase 3 study in second line clear cell RCC patients (a separate trial) was 11.3%, and median progression-free survival (PFS) was 4.8 months.

All patients in TRACON’s Phase 1b study have now completed treatment and the randomized Phase 2b TRAXAR clinical trial of TRC105 in combination with Inlyta is currently enrolling patients with advanced or metastatic RCC. TRACON expects top-line data from the TRAXAR study to be available in the first half of 2017. A Trials-in-Progress poster for the TRAXAR study was also presented at the meeting. The poster presentations are available on the Publications page under the News section of the TRACON website at www.traconpharma.com.

The following key additional data from the Phase 1b study were also presented at the meeting:

The recommended Phase 2 dose of TRC105 of 10 mg/kg dosed weekly was well-tolerated in combination with Inlyta and no dose limiting toxicities were observed.
The most common adverse events were low grade epistaxis, headache, fatigue, diarrhea, and gingival bleeding.
The Inlyta dose was escalated from 5 mg BID to 7 mg BID in 22% of patients and to 10 mg BID in 11% of patients.
Serum concentrations of TRC105 above target concentrations were maintained continuously at the 8 mg/kg and 10 mg/kg TRC105 dose levels.
Plasma levels of TGF-b receptor 3 (betaglycan) at baseline were significantly higher in patients with a partial response, while levels of osteopontin were significantly lower at baseline for patients that achieved a partial response. Both markers correlated with time on study and their potential prognostic/predictive value are being investigated in the Phase 2b TRAXAR study.
About the TRAXAR Phase 2b Clinical Trial in RCC

The Phase 2b TRAXAR clinical trial is a multicenter, open-label, randomized clinical trial of TRC105 in combination with Inlyta versus Inlyta in patients with advanced or metastatic RCC. The primary endpoint of the Phase 2b study is progression-free survival. The company expects to enroll approximately 150 patients who have failed one prior VEGF inhibitor in the study. Patients may have also failed one prior mTOR inhibitor and one prior immunotherapy. For additional information on this clinical trial, please visit www.clinicaltrials.gov, identifier NCT01806064.

About TRC105 (carotuximab)

TRC105 (carotuximab) is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation, and also expressed on fibroblasts, a cell that causes fibrosis. TRC105 is currently being studied in multiple Phase 2 clinical trials sponsored by TRACON or the National Cancer Institute for the treatment of solid tumor types in combination with VEGF inhibitors. The ophthalmic formulation of TRC105, DE-122, is currently in a Phase 1/2 trial for patients with wet AMD. TRC205, a second generation antibody to endoglin, is undergoing preclinical testing in models of fibrosis. For more information about the clinical trials, please visit TRACON’s website at View Source