Tarvacin (bavituximab) / Avid Bioservices, Feng Biosciences - LARVOL DELTA

LAP it up: The role of LC3 Associated Phagocytosis (LAP) in CF (NACFC 2025) - "LAP is reduced in CF macrophages leading to decreased bacterial killing and increased inflammation. Bavituximab has emerged as a potential therapeutic candidate to increase the efficacy of CF macrophages in clearing infection and inflammation in people with CF by restoring LAP."

Immunology • Infectious Disease • Inflammation

A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: David Hsieh | Trial completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor

1922GCCC: Pembro and Bavituximab for Squamous Cell Carcinoma of Head and Neck (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: University of Maryland, Baltimore | Trial primary completion date: Jan 2025 ➔ Sep 2024

Trial primary completion date • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Phosphatidylserine (PS)-targeting chimeric Interferon (IFN) fusion proteins for anti-tumor applications. (PubMed, bioRxiv) - "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."

Journal • Breast Cancer • Melanoma • Oncology • Solid Tumor • ANXA5 • GAS6 • IFNB1

Expression, purification and characterization of phosphatidylserine-targeting antibodies for biochemical and therapeutic applications. (PubMed, Methods Cell Biol) - "Given the importance of PS in cancer immunology and immune escape, PS-targeting monoclonal antibodies have been characterized with promising immunotherapeutic potential. Here, we describe the cloning and characterization of a series of PS targeting antibodies and their potential use and utility in immuno-oncology."

IO biomarker • Journal • Oncology

A phase II study of bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC) (ASCO-GI 2015) - Abstract #345; P2, N=38; "Bavituximab and sorafenib were well tolerated in patients with advanced HCC. When compared with historical controls, combination therapy demonstrated an improvement in TTP and PFS at four months. Combination therapy increases immune tumor infiltrates."

P2 data • Hepatocellular Cancer • Oncology

Development of betabodies: the next generation of phosphatidylserine targeting agents. (PubMed, J Biol Chem) - "PS has been targeted with antibodies, such as bavituximab, that bind the phospholipid via a cofactor, β2-glycoprotein 1 (β2GP1); these antibodies showed excellent specificity for tumor vasculature and induce an immune stimulatory environment...Betabodies bind to externalized PS with high affinity (∼1 nM), without the requirement of a co-factor and localize robustly to the TME. We demonstrate that betabodies are a direct PS-targeting agent that have the potential to be used as anti-tumor therapy, drug delivery vehicles, and tools for imaging the TME."

Journal • Oncology

Clinical Outcomes of Second-Line and Beyond (2L+) Treatments (TXS) in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (aNSCLC): A Systematic Literature Review (SLR) (ISPOR 2024) - "Prior tx with docetaxel or immune checkpoint inhibitors was a common exclusion criterion...All IOs demonstrated significant improvement in OS vs CTs, except bavituximab and avelumab...One study comparing IO ± TT vs CT±TT reported a significant improvement in OS but a decrease in PFS with ramucirumab-pembrolizumab vs CT ± ramucirumab. Another study found significant improvement in OS with durvalumab vs standard of care...Tislelizumab and atezolizumab showed marked improvement per the Core Quality of Life Questionnaire and lung cancer module compared to CT. Consistent with the tx paradigm, IO mono significantly improved median OS and HRQoL. Nivolumab, tislelizumab, and sintilimab also significantly improved PFS."

Clinical • Clinical data • Metastases • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial. (PubMed, Nat Commun) - P2 | "Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment."

IO biomarker • Journal • P2 data • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial (Nature, Nat Commun) - P2 | N=36 | NCT03519997 | "Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3–11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response."

P2 data • Hepatocellular Cancer

The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial (Nature, Nat Commun) - P2 | N=36 | NCT03519997 | "Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3–11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response."

P2 data • Hepatocellular Cancer

Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P2 | N=36 | Completed | Sponsor: Massachusetts General Hospital | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

1922GCCC: Pembro and Bavituximab for Squamous Cell Carcinoma of Head and Neck (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: University of Maryland, Baltimore | Recruiting ➔ Active, not recruiting | N=29 ➔ 7

Enrollment change • Enrollment closed • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TMB

Bavituximab decreases immunosuppressive myeloid-derived suppressor cells in newly diagnosed glioblastoma patients. (PubMed, Clin Cancer Res) - P2 | "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."

Journal • Myeloid-derived suppressor cells • Brain Cancer • CNS Tumor • Glioblastoma • Immune Modulation • Oncology • Solid Tumor

A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: David Hsieh | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Phase 2 study of bavituximab (bavi), a first-in-class antibody targeting phosphatidylserine (PS), plus pembrolizumab (P) in advanced gastric or gastroesophageal junction (GEJ) cancer. (ASCO 2023) - P2 | "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."

IO biomarker • Metastases • P2 data • Anemia • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Microsatellite Instability • Oncology • Solid Tumor • MSI • PD-L1

Bavituximab decreases immunosuppressive myeloid-derived suppressor cells in newly diagnosed glioblastoma patients (Clin Cancer Res) - P2 | N=36 | NCT03139916 | "Thirty-three adults with isocitrate-dehydrogenase-wild-type GBM received 6 weeks of concurrent chemoradiation, followed by 6 cycles of temozolomide (C1-C6). Bavituximab was given weekly, starting week 1 of chemoradiation, for at least 18 weeks....The study met its primary endpoint with an OS-12 of 73% (95% CI 59-90%). Decreased pre-C1 rCBF (HR 4.63, p=0.029) and increased pre-C1 Ktrans were associated with improved OS (HR 0.09, p=0.005). Pre-treatment, overexpression of myeloid-related genes in tumor tissue was associated with longer survival. Post-treatment, tumor specimens contained fewer immunosuppressive MDSCs (p=0.01)."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: David Hsieh | Trial completion date: Apr 2024 ➔ Apr 2025 | Trial primary completion date: Apr 2023 ➔ Apr 2024

Metastases • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Aberrantly exposed phosphatidylserine as a drug delivery target in pancreatic cancer (AACR 2023) - "To this point, PS has been targeted with antibodies, such as Bavituximab, that have shown excellent specificity for tumor vasculature and an immune stimulatory environment evidence by polarization of macrophages to a pro-inflammatory M1-like phenotype, a reduction in myeloid-derived suppressor cells, enhanced maturation of dendritic cells and increased primed T cell activity...The mechanism of action has not yet been fully elucidated; however, it may involve the interaction between the β2GP1 domains and endogenous LPS. This first-in-class tumor targeting therapeutic has potential to provide efficacy in therapy-resistant pancreatic tumors via targeted drug delivery as well as modulation of the immuno-microenvironment like its PS targeting predecessors."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Targeting anticancer agents to the tumor microenvironment with cathepsin B cleavable drug-linker conjugates of phosphatidylserine-binding proteins (AACR 2023) - "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."

Biomarker • Tumor microenvironment • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CTSB

1922GCCC: Pembro and Bavituximab for Squamous Cell Carcinoma of Head and Neck (clinicaltrials.gov) - P2 | N=29 | Recruiting | Sponsor: University of Maryland, Baltimore | Trial completion date: Jan 2025 ➔ Jan 2027 | Trial primary completion date: Jan 2023 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TMB

MRI CHANGES IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS TREATED AS PART OF A PHASE II TRIAL WITH BAVITUXIMAB, RADIATION, AND TEMOZOLOMIDE (SNO 2018) - P2; ": Combining bavituximab with radiation and temozolomide results in decreased enhancing tumor volume, permeability, and cerebral perfusion. Continued patient accrual and imaging marker evaluation are underway to investigate the correlation between bavituximab, MRI changes, and survival."

Clinical • P2 data • Brain Cancer • Oncology • Solid Tumor

Targeting phosphatidylserine enhances the antitumor response to radiation therapy and immune checkpoint blockade in a preclinical melanoma Model (SITC 2018) - P1b/2; "Finally, we found an increase of PS expression on immune cells in the blood of melanoma patients 4-7 days post RT supporting the rationale for translating of this therapy into the clinic. Conclusions This finding highlights the potential of combining these agents to improve outcome in patients that are refractory to anti-PD-1 and may inform the design of future clinical trials with the human PS targeting antibody (Bavituximab) in multiple cancers"

Checkpoint inhibition • IO biomarker • PD(L)-1 Biomarker • Preclinical • Melanoma

Phase 2 trial of pembrolizumab (pembro) and bavituximab (bavi) in advanced hepatocellular carcinoma (HCC). (ASCO-GI 2023) - P2 | "The combination of bavi and pembro appears to be well tolerated in this patient population and has a toxicity profile comparable to monotherapy immune checkpoint inhibitor. Preliminary analyses suggests that bavi and pembro may have promising anti-tumor activity in advanced HCC. Clinical trial information: NCT03519997."

Metastases • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Final clinical results from SUNRISE: A phase III, randomized, double-blind, placebo-controlled multicenter trial of bavituximab plus docetaxel in patients with previously treated stage IIIb/IV nonsquamous non-small cell lung cancer (ESMO 2017) - P3; "The combination of B+D was well-tolerated though no OS difference was observed compared to D alone in the ITT population of previously treated nonsquamous NSCLC. An exploratory analysis of patients who received subsequent ICI found significantly longer OS in patients who received prior B+D than those who received D and support further clinical investigation of B+ICI in NSCLC."

Biomarker • Checkpoint inhibition • Clinical • P3 data • Non Small Cell Lung Cancer