Tarvacin (bavituximab)

P2, N=7, Active, not recruiting, University of Maryland, Baltimore | Trial primary completion date: Jan 2025 --> Sep 2024

Several strategies have been envisioned to target dysregulated PS in the tumor microenvironment including PS binding proteins such as Annexin V and PS-targeting monoclonal antibodies (Bavituximab) with promising preclinical results...In vivo , Gas6-IFN-β-IFN-λ retain strong anti-tumor activities in a syngeneic model when expressed ectopically in a E0771 breast cancer model and B16-F10 melanoma models. Collectively, we report on the generation and utility of a series of novel in class IFN fusion proteins that target the immune stimulatory features of IFNs to the PS externalization in the tumor microenvironment.

P2, N=36, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed

P2, N=7, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting | N=29 --> 7

Bavituximab has activity in newly diagnosed GBM and resulted in on-target depletion of intratumoral immunosuppressive MDSCs. Elevated pre-treatment expression of myeloid-related transcripts in GBM may predict response to bavituximab.

P2, N=36, Active, not recruiting, David Hsieh | Recruiting --> Active, not recruiting

The combination of Bavi and P was well tolerated; observed AEs were consistent with known profiles for each agent. Higher ORRs were observed in CPI-naïve patients with B+ status and baseline NLR<4, and of note, in patients with PD-L1 CPS <1. Future studies may be planned to confirm the activity of Bavi in combination with P with patient selection based on a particular genetic signature.

P2, N=29, Recruiting, University of Maryland, Baltimore | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Jan 2023 --> Jan 2025

The payloads include benzosuberene-based aniline KGP156 and its phenolic congener KGP18, dihydronaphthalene-based KGP05, and indole-based OXi8006. Conjugation of thiolated Bavituximab with Mc-Val-Cit-PABC-KGP156 gave a drug/antibody ratio (DAR) of 3.6/1 after cleavage by cathepsin B and determination of released KGP156 by LC-MS. These studies revealed 1) distinct differences in cleavage rates for drug-linkers, 2) cleavage by cathepsin L, and 3) efficient cathepsin B mediated release of payload from the ADC.

P2 | N=28 | NCT03519997 | "OncXerna Therapeutics, Inc....announced final results from a Phase 2 trial of bavituximab plus pembrolizumab in patients with previously untreated advanced hepatocellular carcinoma and new biomarker data demonstrating that the Xerna TME Panel clearly identified trial participants more likely to benefit from treatment. The data were featured in a poster that was presented on January 20, 2023 at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI)....In the study featured in the ASCO GI poster, pre-treatment tumor biopsies were analyzed using the Xerna TME Panel and findings were correlated with objective tumor response to test the hypothesis that tumors with high immune scores (immune active or immune-suppressed TME subtypes [biomarker-positive]) are more likely to respond to bavituximab plus pembrolizumab than those with low immune scores (angiogenic or immune-desert TME subtypes [biomarker-negative])."

The combination of bavi + pembro is well tolerated and active in gastric cancer, including in patient with CPS<1, a group less responsive to CPI. In addition, the Xerna™ TME Panel was likely predictive of treatment response. Retrospective analysis suggests baseline NLR may have a prognostic or predictive role.

In Regimen B (800 mg), one partial response was reported in a subject with MSS-CRC treated for 263 days, and one prolonged stable disease (227 days) was reported in a gastric cancer (GC) subject previously treated with pembrolizumab plus bavituximab for less than 3 months due to progression; both subjects are continuing study treatment . Dose escalation of GB1275, up to 1200 mg in Regimens A and B, demonstrated tolerability as monotherapy and combined with pembrolizumab in subjects with advanced cancers . Encouraging antitumor activity in Regimen B (800 mg) was observed in subjects with MSS-CRC and GC . Biological activity reflected by MDSC modulations in blood and TIL Increases in tumor biopsies with GB1275 alone and with pembrolizumab supports the mechanism of GB1275 .