Phase 1b study of AVB-500 in combination with paclitaxel or pegylated liposomal doxorubicin platinum-resistant recurrent ovarian cancer.
Gynecol Oncol
; 163(2): 254-261, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34474927
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
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Recombinant Fusion Proteins
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Antineoplastic Combined Chemotherapy Protocols
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Carcinoma, Ovarian Epithelial
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Neoplasm Recurrence, Local
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adult
/
Aged
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Aged80
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Female
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Humans
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Middle aged
Language:
En
Journal:
Gynecol Oncol
Year:
2021
Document type:
Article