Ramucirumab in pediatric and young adult patients (Pts) with relapsed/refractory (R/R) desmoplastic small round cell tumor (DSRCT) or synovial sarcoma (SS): Results from the CAMPFIRE study.

Abstract

11574 Background: Few effective therapies exist for pts with R/R DSRCT and SS, and hence, their prognosis remains poor. Preclinical data suggested the relevance of vascular endothelial growth factor receptor 2 (VEGFR2) inhibition in these diseases. We evaluated the efficacy of ramucirumab (RAM, VEGFR2 receptor antagonist) + chemotherapy vs. chemotherapy alone in pediatric and young adult pts with R/R DSRCT (JV01) or SS (JV02). Methods: JV01 and JV02 were randomized, global, multicenter, Phase 1/2 studies in pts aged ≤29 years with R/R DSRCT or SS and evaluated pts treated with RAM + cyclophosphamide/vinorelbine (CV; JV01) and RAM + gemcitabine/docetaxel (GD; JV02). Pts were randomized 2:1 to the experimental and control groups. The primary endpoint was progression-free survival (PFS) per RECIST v1.1, analyzed via a Bayesian hierarchical model allowing adaptive borrowing on effect size (log hazard ratio [HR]) between JV01 and JV02 and control arm augmentation with historical (real world) data. Interim futility required a probability (Pr) of PFS (HR < 1) > 60%, and intervention success at final analysis was declared at Pr > 99%. Frequentist analysis (1-sided α = 0.1) was performed as a sensitivity analysis. Safety was a secondary endpoint. Results: Baseline characteristics were balanced between the treatment arms in both studies: RAM+CV, n = 20; CV, n = 10; RAM+GD, n = 16; GD, n = 7. JV02 met the futility criterion (Table) and was suspended without completing enrollment. JV01 fully enrolled but did not meet the primary endpoint at the final analysis (PFS HR = 0.7, 98% credible interval = 0.3, 1.7; pr [HR < 1] = 86.4% vs. 99%). However, frequentist analysis in JV01 showed that pts in the RAM+CV arm had a numerical improvement of 5 months in median PFS vs. the CV arm. Overall, no significant safety events were reported in either study. Conclusions: The PFS outcome was not met for either rare disease. The numerical trend in JV01 is noteworthy, especially considering the limited treatment options available for DSRCT. Safety was consistent with the known profiles of the individual treatments and the population. Clinical trial information: NCT04145700 , NCT04145349 . JV01 JV02 RAM+CV (n=20) CV (n=10) HR(80% CrI) b RAM+GD (n=16) GD (n=7) HR (80% CrI) b Median PFS (months), 98% Crl a Median PFS (months), 98% Crl a Primary Bayesian Analysis 5.7(3.2, 10.0) 3.7(1.8, 8.3) 0.7(0.3, 1.7)Pr (HR <1) = 86.4 % 3.7(1.5, 11.5) 6(2.1, 18.0) 1.8(0.8, 3.1)Pr (HR <1) = 20.1% PFS events, n 16 8 9 5 Frequentist Analysis c 6.8(5.5, 10.4) 1.7(1.4, 2.7) 0.5(0.3, 0.8)p = 0.082 2.1(1.9, 6.1) 2.0 (1.4, NR) 0.7(0.3, 1.5)p = 0.544 CI = confidence interval; CrI = credible interval; CV = cyclophosphamide/vinorelbine; GD = gemcitabine/docetaxel; HR = hazard ratio; NR = not reached; PFS = progression-free survival; Pr = probability; RAM = ramucirumab. a Posterior median. b Posterior mean displayed. c 80% CI for JV01 and JV02.