1697P - Phase II randomized double-blind trial of axitinib (Axi) +/- PF 04518600, an OX40 antibody (PFOX) after PD1/PDL1 antibody (IO) therapy (Tx) in metastatic renal cell carcinoma (mRCC): Final analysis

Background

Resistance to IO Tx continues to result in poor outcomes. OX40 (CD-134) mediates IO resistance. Co-stimulatory PFOX activates exhausted T-cells, and dendritic cells and increases proliferation, effector function, and survival of T cells. We hypothesized that PFOX + Axi would improve progression free survival (PFS) vs. Axi in patients (pts) with mRCC after IO Tx. The interim analysis (IA), tested this hypothesis when ≥ 33 events were observed, and rejected it (p = 0.0089) and the study was subsequently closed to new accrual.

Methods

Pts with clear cell mRCC were stratified for IMDC risk groups then randomized 1:1 to Axi 5mg po bid + PFOX 0.3mg/kg iv (Arm 1) or placebo (PL) iv (Arm 2) on Day 1 of a 2-week cycle. The primary endpoint was PFS expecting a hazard ratio (HR) of 0.5 favoring Arm 1; secondary endpoints were overall survival (OS), objective response rate (ORR), duration of response (DOR) per RECIST v1.1, and safety/tolerability.

Results

Between Feb 2018 and Oct 2021 a total of 60 pts were randomly assigned and treated with Axi+PFOX (N=30) or Axi+PL (N=30). As of April 2024, 51 PFS events had occurred. The study did not meet its primary endpoint of PFS. At a median follow up of 37.8 mo, median PFS was 9.5 (95% CI: 5.9-14.5) mo. for Arm 1 vs. 8.5 (95% CI: 5.5-11) mo. for Arm 2 (HR=1.02 [95% CI: 0.59-1.78] p=0.93). After adjusting by prior lines of Tx, HR=0.96 [95% CI: 0.55-1.68] p=0.89. Median OS was Arm1: 27.8 (95% CI: 18.9, 53.3) vs. Arm2: 35.7 (95% CI: 13.3, NA) (adjusted HR=1.10 [95% CI: 1.06 -4.74], adjusted by performance status, IMDC risk group and prior lines of Tx, p=0.79). Median DOR Arm1: 10.5 (range: 3.5-16.6) mo. vs Arm2 7.4 (range: 1.8-18.4) mo. 5 pts discontinued Tx due to TRAE, 3 in Arm 1 (1 grade 3 hypertension, 1 grade 2 stroke, 1 grade 3 bullous dermatitis) and 2 in Arm 2 (1 grade 4 ALT and 1 grade 3 AST elevation). Table: 1697P

Conclusions

In IO-pretreated mRCC pts, Axi + PFOX did not improve PFS compared to Axi alone.

Clinical trial identification

NCT03092856.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Pfizer.

Disclosure

All authors have declared no conflicts of interest.