Orego is an anti-CA 125 cancer vaccine whereas nivo is a programmed death-1 inhibitor. Both agents are clinically active in advanced EOC. We hypothesize that their combination will elicit a systemic CA 125-specific T cell response which is synergistic, safe and clinically efficacious in rEOC patients (pts).
Pts with rEOC, fallopian tube or primary peritoneal carcinoma who have received ≥2 prior chemotherapy lines were recruited in this phase Ib/IIa study. Study objectives were to characterize the safety and tolerability of orego + nivo, and determine the recommended dose for expansion (RDE)/recommended phase II dose (RP2D) of this combination. Using a modified 3 + 3 design, pts were treated starting at orego 2mg Q4W (dose level 1) + nivo 240mg Q2W. 2 lower doses of orego were specified in case of dose-limiting toxicities (DLT). A minimum of 6 and maximum of 18 pts would be accrued for dose finding. Additional 14 pts will be treated at RP2D in the dose expansion cohort.
6 pts with median age 61 years (range 52.0 – 63.0) and ECOG performance status 1 were treated at dose level 1. All had EOC (4 high grade serous, 2 clear cell) and a median of 4 (range 3 – 9) treatment lines before study entry. No DLT were observed. Treatment-related adverse events (AE) included grade 1 events of arthralgia, rash, transaminitis, fatigue, and anorexia. 2/6 (33.3%) pts experienced grade 1-2 thyroid-related immune-related AE. 5 serious adverse events (SAE) were observed but they were deemed unlikely/not related to study treatment, including 2 episodes of grade 4 sepsis in 1 pt who eventually died of progressive disease (PD). Dose delay of orego and nivo occurred in 1 pt because of hospitalization for fever (SAE) followed by scheduling reasons. Dose omissions of nivo occurred in 2 pts due to grade 4 sepsis in 1 pt, and grade 1 thyroiditis in another. Analysis of exploratory immune correlate(s) is underway and will be reported at the meeting.
Orego 2mg Q4W with nivo 240mg Q2W was selected as the RDE/RP2D to treat rEOC. Further evaluation of safety and efficacy of this novel combination is ongoing in our dose expansion cohort.
Clinical trial identification
Legal entity responsible for the study
National Cancer Centre Singapore.
J.J. Chan: Advisory role: Eisai, Pfizer; Travel, Accommodations, Expenses: Synthon, Novartis, Pfizer. T.J.Y. Tan: Advisory role: Novartis, Pfizer; Research funding: Bayer, Novartis; Travel, Accommodations, Expenses: Merck Sharp & Dohme, Eisai, Pfizer. J.W.K. Chia: Honoraria: AstraZeneca; Consulting or Advisory role: Tessa Therapeutics, Biomark, Aslan Pharmaceuticals, MSD, AstraZeneca, Roche; Research funding: Bayer, Bristol Myers Squibbs; Travel, Accommodations, Expenses: AstraZeneca, Bristol Myers Squibbs. All other authors have declared no conflicts of interest.