What To Look Out For In Glioblastoma At ASCO

Highlights of abstracts at the upcoming American Society of Clinical Oncology meeting include early studies in recurrent glioblastoma from Bristol-Myers Squibb Co., Tracon Pharmaceuticals Inc.andZiopharm Oncology Inc., according to a meeting preview from BioMedTracker.

Glioblastoma multiforme is a high-risk space, considering all of the past trial failures, but it also offers rewards for sponsors that succeed in even marginal improvements and researchers are hopeful about the potential of checkpoint inhibitors (see related story, (Also see "Can Checkpoint Inhibitors Jump-Start Glioblastoma Drug Development?" - Pink Sheet, 23 May, 2016.)).

Bristol is presenting updated data from the first cohort of the CheckMate 143 study at the ASCO meeting, which will be held June 3-7 in Chicago.

One ASCO abstract (#2014) includes data for 20 patients with recurrent GBM who took the PD-1 inhibitor Opdivo (nivolumab) alone versus two different doses of a combination with CTLA-4 inhibitor Yervoy (ipilimumab).

According to the study abstract, the 12-month overall survival rate was 40% for Opdivo alone versus 30% or 25% for the combination of Yervoy/Opdivo, depending on the dose – figures that BioMedTracker described as "encouraging."

Opdivo alone was also better tolerated than the combination, "consistent with observations in other tumor types," analysts noted.

Bristol said it will be presenting additional, updated data at the meeting.

BioMedTracker analysts also dubbed Tracon as one of six companies to watch at the meeting, based on Phase II recurrent GBM data for TRC105 (Abstract #2035). The candidate is a first-in-class human chimeric monoclonal antibody that binds to CD105 (endoglin), a receptor over-expressed on proliferating endothelium that is required for angiogenesis. The drug has shown efficacy in kidney cancer in the past and with its novel mechanism could play a role for multiple cancers treated with Roche's Avastin (bevacizumab), the analysts noted.

The study tested TRC1-5 with Avastin in Avastin-refractory patients. Median overall survival for 15 patients in the study taking the combination was 5.75 months, "which is higher than the 4 month OS historical control data for [bevacizumab]-refractory GBM, but a larger controlled study is necessary to determine the actual clinical benefit," the report notes. The combination was also well-tolerated.

'While these are early results in only 15 patients, we believe that the benefit of the combination of TRC105 in bevacizumab-naive patients could be even greater as endoglin upregulation is hypothesized to be a VEGF inhibitor escape pathway," the report adds.

The combination is in Phase II for Avastin-naïve GBM.

Ziopharm's updated Phase I results for its adenovector-based technology-based candidate Ad-RTS-hiL-12 in combination with oral veledimex (IXN-1001), an activator ligand, in heavily pretreated, recurrent glioma, including GBM, at ASCO are also noteworthy.

One injection of Ad-RTS-hIL-12 was administered into patients' brain tumors and veledimex was given orally to activate production of IL-12, an anti-cancer cytokine, and an immune response at the tumor site, the abstract notes (#2052).

"Even at its lowest dose, the presence of IL-12 in the bloodstream could be detected, demonstrating that veledimex is bioavailable and crosses the blood-brain barrier at sufficient levels," the investigators reported.

With follow-up of 6.2 months, 10 of 11 patients were alive.

BioMedTracker analysts said that the "results confirm the ability to trigger an immune response in brain tumor cells via an oral agent and are encouraging for the further development of this adenoviral vector-based technology."