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Phase 1b study of AVB-500 in combination with paclitaxel or pegylated liposomal doxorubicin platinum-resistant recurrent ovarian cancer
- Source :
- Gynecologic oncology. 163(2)
- Publication Year :
- 2021
-
Abstract
- Objective GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study ( NCT03639246 ) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D). Methods Eligible patients received AVB-500 at 10, 15, or 20 mg/kg IV q2wk combined with PAC (n = 23) or PLD (n = 30). Patients were treated until progression or unacceptable toxicity. All were followed for survival. Results No dose limiting toxicities were observed and serum GAS6 was completely suppressed across the three dose levels evaluated. AVB-500 + PAC yielded better clinical activity than AVB-500 + PLD with an ORR of 34.8% (8/23, 2 complete responses) and median DoR, PFS, and OS of 7.0, 3.1, and 10.3 months, respectively. Subgroup analyses showed AVB-500 + PAC patients who had no prior bevacizumab or whose AVB-500 trough levels were >13.8 mg/L exhibited the best clinical response. The ORR and median PFS and OS in patients with these characteristics were ≥50%, ≥7.5 months, and ≥19 months, respectively. Given AVB-500 nor the combination with chemotherapy was expected to cause DLTs, the RP2D of AVB-500 was 15 mg/kg identified using an MIDD approach. Conclusion 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.
- Subjects :
- Oncology
Adult
medicine.medical_specialty
Bevacizumab
Paclitaxel
medicine.medical_treatment
Recombinant Fusion Proteins
Population
Carcinoma, Ovarian Epithelial
Targeted therapy
Polyethylene Glycols
chemistry.chemical_compound
Internal medicine
Proto-Oncogene Proteins
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
education
Aged
Aged, 80 and over
Ovarian Neoplasms
Chemotherapy
education.field_of_study
GAS6
business.industry
Obstetrics and Gynecology
Receptor Protein-Tyrosine Kinases
Middle Aged
medicine.disease
Axl Receptor Tyrosine Kinase
chemistry
Doxorubicin
Drug Resistance, Neoplasm
Toxicity
Intercellular Signaling Peptides and Proteins
Female
Neoplasm Recurrence, Local
Ovarian cancer
business
medicine.drug
Subjects
Details
- ISSN :
- 10956859
- Volume :
- 163
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Gynecologic oncology
- Accession number :
- edsair.doi.dedup.....e1fe8fce6bd84ed72e9b2ed9d83891ba