batiraxcept (AVB-500)

Batiraxcept effectively reduced serum GAS6 levels at 1-h post-treatment, resulting in trough levels below the limit of detection in all cases but one. In conclusion, the combination of batiraxcept and durvalumab was safe and tolerable but did not demonstrate anti-tumor activity in a heterogenous population of patients with recurrent PROC.

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Aug 2033 --> Nov 2033 | Initiation date: Dec 2023 --> Mar 2024 | Trial primary completion date: Aug 2028 --> Nov 2028

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | N=19 --> 12

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Apr 2033 --> Aug 2033 | Initiation date: Sep 2023 --> Dec 2023 | Trial primary completion date: May 2028 --> Aug 2028

P1b/2, N=72, Terminated, Aravive, Inc. | Trial completion date: Mar 2025 --> Aug 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Aug 2023; Due to business reasons

P3, N=366, Terminated, Aravive, Inc. | There was no detriment to overall survival. No new safety signals were identified.

P1b/2, N=34, Terminated, Aravive, Inc. | N=99 --> 34 | Trial completion date: Oct 2025 --> Aug 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2024 --> Aug 2023; Due to business reasons

P1, N=19, Active, not recruiting, University of Oklahoma | Trial primary completion date: Aug 2023 --> Jan 2024

Table: 1889P Conclusions BT + cabo demonstrated acceptable tolerability and promising efficacy in treatment-refractory ccRCC pts. BT + cabo will be further studied in a P3 trial of 2L+ ccRCC patients whose disease has progressed following IO and VEGF-TKI therapies.

P1, N=36, Not yet recruiting, Washington University School of Medicine

Most importantly, AVB-500 was highly effective at decreasing tumor dissemination of bile duct tumor cells in the peritoneal cavity. This study strongly supports the idea of using the AXL receptor as a new therapeutic target to treat the growth and progression of biliary cancer.

P1b/2, N=53, Completed, Aravive, Inc. | Active, not recruiting --> Completed

P1b/2, N=99, Recruiting, Aravive, Inc. | Trial completion date: Apr 2024 --> Oct 2025 | Trial primary completion date: Apr 2023 --> Oct 2024

P1b/2, N=80, Active, not recruiting, Aravive, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jul 2023 --> Mar 2025 | Trial primary completion date: Dec 2022 --> Dec 2024

We showed that chemotherapy-resistant endometrial cancer cells (ARK1, uterine serous carcinoma and PUC198, grade 3 endometrioid adenocarcinoma) had improved sensitivity and synergy with paclitaxel and carboplatin when treated in combination with AVB-500. Finally, multiple glycolytic metabolites were lower in the tumors treated with AVB-500 + paclitaxel than in tumors treated with paclitaxel alone. Our study provides strong pre-clinical rationale for combining AVB-500 with paclitaxel in aggressive endometrial cancer models.

The GAS6/AXL inhibitor AVB-500 potentiated the effect of Trastuzumab to decrease uterine serous cancer cell proliferation and invasion in vitro and tumor burden in vivo. There was co-localization of AXL and HER2 receptors seen in both uterine serous cancer cell lines. Our data suggest that the addition of AVB-S6-500 increased the therapeutic efficacy of Trastuzumab therapy in uterine serous cancers.

Learning Objective: Conclude that the combination of Trastuzumab and AVB500 lead to decrease uterine serous cancer cell proliferation and invasion in vitro and tumor burden in vivo in uterine serous cancer cell lines that express both AXL and HER2/neu receptors.

In addition, intraperitoneal mouse models demonstrated a significant decrease in tumor burden in two cell lines. The combination of AVB-500 and bevacizumab reduced tumor burden in vivo and reduced morphogenesis and migration in vitro which are vital to the process of angiogenesis.

Compared to chemotherapy alone, AVB-500 plus carboplatin and/or paclitaxel led to decreased ovarian cancer cell survival in vitro and tumor burden in vivo. Implications: GAS6/AXL is a novel target to sensitize ovarian cancers to carboplatin and olaparib. Additionally, GAS6 levels can be associated with response to carboplatin treatment.

Key eligibility criteria: ≥ 18 years, histologically confirmed metastatic ccRCC, and progression after 1st line therapy. Enrollment began December 2020.

P1b/2, N=53, Active, not recruiting, Aravive, Inc. | Trial primary completion date: Dec 2021 --> Jan 2021

AVB-500 was well-tolerated in combination with PAC or PLD and contributed to the clinical activity of PAC in PROC patients. Subgroup analyses identified a population of PROC patients who may benefit the most from AVB-500 treatment, which will be further assessed in an ongoing Phase 3 PROC trial.

We demonstrate that the addition AVB-500 to paclitaxel improves endometrial cancer chemo-sensitivity. We show that this therapeutic combination decreases basal glycolysis through reduced PI3K/AKT signaling. This provides a metabolic mechanism for increasing uterine cancer sensitivity to chemotherapy.

P1b/2, N=80, Recruiting, Aravive, Inc. | Not yet recruiting --> Recruiting

P3, N=500, Recruiting, Aravive, Inc. | Not yet recruiting --> Recruiting

The purpose of this study was to evaluate safety, tolerability, and preliminary efficacy of AVB-500 in combination with pegylated liposomal doxorubicin (PLD) and paclitaxel (Pac) and determine the RP2D...Exploratory analysis also suggested that improved response rates may be observed in patients who have not been exposed to bevacizumab. AVB-500 is a novel Fc fusion protein that binds the GAS6 ligand and targets GAS6/AXL pathway. AVB-500was found to be safe and tolerable in this Ph1B trial in combination with Paclitaxel or PLD. The RP2D was based upon PK/PD parameters.

We hypothesized that GAS6 inhibition with AVB-500 (AVB) sensitizes platinum-resistant cells to platinum chemotherapy by stalling replication forks and increasing replication stress...For DNA fiber assays, cells were labeled with the thymidine analog IdU for 20 minutes followed by CldU for 60 minutes and treatment with carbo, cisplatin (cis), or AVB...Combenefit analyses confirmed AVB and carboplatin were synergistic... Inhibition of the GAS6 pathway with AVB improves sensitivity of platinum-resistant cells to platinum chemotherapy by increasing replication stress and DNA damage and decreasing HR. GAS6 is a potential biomarker predictive of poor response to platinum-based neoadjuvant chemotherapy and might identify patients who would benefit from treatment with AVB.

No abstract available

No abstract available

P3, N=500, Not yet recruiting, Aravive, Inc.

P1b/2, N=53, Active, not recruiting, Aravive, Inc. | Recruiting --> Active, not recruiting | N=196 --> 53

Our objective was to determine whether GAS6/AXL inhibition with AVB500 (AVB) can increase platinum and poly(ADP-ribose) polymerase inhibitor (PARPi) response through inducing "BRCAness" in sporadic high-grade serous ovarian cancer (HGSC) models and identify the ligand GAS6 as a marker for poor response to platinum...Patient-derived xenograft (PDX) and OVCAR5 intraperitoneal (IP) mouse models were used to determine response to carboplatin, paclitaxel, and AVB (C+P+A) as well as olaparib and AVB (O+A)... Inhibition of this GAS6/AXL pathway with AVB induces BRCAness in sporadic HGSC, which leads to an improved sensitivity to carboplatin and olaparib. In addition, high levels of GAS6 can identify patients who have worse response to platinum-based chemotherapy and may benefit from this novel GAS6/AXL inhibitor.

Our objective was to determine whether GAS6/AXL inhibition with AVB500 (AVB) can increase platinum and poly(ADP-ribose) polymerase inhibitor (PARPi) response through inducing "BRCAness" in sporadic high-grade serous ovarian cancer (HGSC) models and identify the ligand GAS6 as a marker for poor response to platinum...Patient-derived xenograft (PDX) and OVCAR5 intraperitoneal (IP) mouse models were used to determine response to carboplatin, paclitaxel, and AVB (C+P+A) as well as olaparib and AVB (O+A)... Inhibition of this GAS6/AXL pathway with AVB induces BRCAness in sporadic HGSC, which leads to an improved sensitivity to carboplatin and olaparib. In addition, high levels of GAS6 can identify patients who have worse response to platinum-based chemotherapy and may benefit from this novel GAS6/AXL inhibitor.

Our objective was to determine whether GAS6/AXL inhibition with AVB500 (AVB) can increase platinum and poly(ADP-ribose) polymerase inhibitor (PARPi) response through inducing "BRCAness" in sporadic high-grade serous ovarian cancer (HGSC) models and identify the ligand GAS6 as a marker for poor response to platinum...Patient-derived xenograft (PDX) and OVCAR5 intraperitoneal (IP) mouse models were used to determine response to carboplatin, paclitaxel, and AVB (C+P+A) as well as olaparib and AVB (O+A)... Inhibition of this GAS6/AXL pathway with AVB induces BRCAness in sporadic HGSC, which leads to an improved sensitivity to carboplatin and olaparib. In addition, high levels of GAS6 can identify patients who have worse response to platinum-based chemotherapy and may benefit from this novel GAS6/AXL inhibitor.