Abstract 1627P
Background
Chemotherapy regimens remain the standard 1L treatment for PC, but with limited anti-tumor activity. We amid to explore the feasibility of adding the PARPi fuzuloparib to mFOLFIRINOX in pts with LA/M PC.
Methods
This was a dose escalation (ESC) and expansion (EXP) phase Ib study. Pts were given oral fuzuloparib at escalating doses starting at 30 mg bid plus intravenous mFOLFIRINOX q2w for 8–12 cycles, followed by maintenance fuzuloparib at 150 mg bid. Dose-limiting toxicities (DLTs) were observed during the first 2 cycles. At least 1 dose cohort would be selected for EXP to collect data supporting the determination of recommended phase II dose (RP2D). Primary endpoints were DLT, maximal tolerated dose (MTD), and RP2D.
Results
As of Jan 15, 2023, 39 pts were recruited. Of them, 12 pts were enrolled in ESC phase (30 mg [n=4]; 60 mg [n=6]; 100 mg [n=2]). DLT occurred in 1 pt in 60 mg cohort (grade 4 decreased platelet count and grade 4 decreased neutrophil count lasting for ≥5 d) and 1 pt in 100 mg cohort (grade 4 decreased neutrophil count lasting for ≥5 d). Based on the tolerability and safety data during ESC, 60 mg bid was determined to be the MTD. 60 and 30 mg cohorts were expanded to 22 and 15 pts, respectively. Overall, grade ≥3 treatment-related adverse events (TRAEs) were reported in 34 (87.2%) of 39 pts; the most common were decreased neutrophil count, decreased platelet count, decreased white blood cell count, and anemia. TRAEs led to discontinuation of any study agent in 5 (12.8%) pts. Efficacy in 60 mg cohort seemed to be most favorable, with ORR of 50.0%, DCR of 94.4%, median PFS of 7.2 mo, and median OS of 12.5 mo (Table). Table: 1627P
Efficacy outcomes
| 30 mg | 60 mg | 100 mg | Overall | |
| Confirmed ORR∗, n/N (%; 95% CI) | 2/12 (16.7%; 2.1–48.4) | 9/18 (50.0%; 26.0–74.0) | 0/2 (0.0%; 0.0–84.2) | 11/32 (34.4%; 18.6–53.2) |
| Confirmed DCR∗, n/N (%; 95% CI) | 10/12 (83.3%; 51.6–97.9) | 17/18 (94.4%; 72.7–99.9) | 1/2 (50.0%; 1.3–98.7) | 28/32 (87.5%; 71.0–96.5) |
| PFS# | ||||
| Events, n/N (%) | 10/15 (66.7%) | 12/22 (54.5%) | 2/2 (100.0%) | 24/39 (61.5%) |
| Median (95% CI), mo | 7.5 (1.9–10.1) | 7.2 (5.1–13.9) | 7.2 (1.6–NR) | 7.3 (5.3–10.1) |
| OS# | ||||
| Events, n/N (%) | 10/15 (66.7%) | 15/22 (68.2%) | 1/2 (50.0%) | 26/39 (66.7%) |
| Median (95% CI), mo | 11.5 (4.0–NR) | 12.5 (7.8–NR) | NR (2.0–NR) | 11.5 (7.8–14.2) |
∗tumor response evaluable set; # full analysis set.
Conclusions
1L fuzuloparib plus mFOLFIRINOX followed by maintenance fuzuloparib was generally safe, with no unexpected toxicities, and showed encouraging efficacy in pts with LA/M PC. The RP2D of fuzuloparib combination was 60 mg bid.
Clinical trial identification
NCT04228601.
Editorial acknowledgement
Legal entity responsible for the study
Jiangsu Hengrui Pharmaceuticals.
Funding
Jiangsu Hengrui Pharmaceuticals.
Disclosure
Z. Sheng, J. Lian, Q. Shi: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals. All other authors have declared no conflicts of interest.
Resources from the same session
1701P - Cancer premium: Explaining differences in prices for cancer vs non-cancer drugs with efficacy and epidemiological endpoints in the US, Germany, and Switzerland
Presenter: Miquel Serra-Burriel
Session: Poster session 22
1702P - Real-world evidence contributions to European medicines agency’s safety and efficacy evaluations of oncology targeted therapies between 2018-2022
Presenter: Jeroen W. G. Derksen
Session: Poster session 22
1703P - Value of molecular targets and genome-targeted cancer therapies FDA-approved, 2015-2022
Presenter: Ariadna Tibau
Session: Poster session 22
1704P - Clinical benefit of cancer drugs approved by the US food and drug administration based on appropriateness of control arm and its change over time
Presenter: Molto Consolacion
Session: Poster session 22
1705P - Therapeutic value of first vs supplemental indications of drugs in the US and Europe (2011-2020): Retrospective cohort study
Presenter: Kerstin Vokinger
Session: Poster session 22