LBA54 Ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in previously untreated HER2 positive locally advanced or metastastic esophagogastric adenocarcinoma (EGA): Results of the randomized phase II INTEGA trial (AIO STO 0217)

Abstract

In 1st line EGA, the addition of PD-1 inhibitors to chemotherapy improved outcome in selected patient populations. The INTEGA trial compared different immunotherapy regimens in 1st line HER2+ EGA. INTEGA is a randomized exploratory phase II investigator initiated trial with two experimental arms. Patients (pts) with previously untreated (for advanced disease) HER2+ (local status - IHC3+ or 2+/ISH+) EGA were randomized to receive trastuzumab (trast) and nivolumab (nivo) (240mg or 1mg/kg with ipi) in combination with either ipilimumab (ipi) (4x 3mg/kg every 3 weeks) (arm A) or mFOLFOX6 (arm B) for up to 12 months. The 1° endpoint was to increase the 12month overall survival rate ([email protected]) from 55% (trast/chemo - ToGA regimen) to 70% in each arm. Between March 2018 and May 2020 a total of 97 pts were enrolled and 88 randomized (44 per arm) in 21 German sites. Baseline characteristics were female/male 18/70, median age 61 (range 41-80), ECOG 0/1 54/34, GEJ/stomach 66/22, prior surgery for primary tumor in 24 patients and were well balanced between groups. Central posthoc biomarker analysis (ongoing) yet showed PD-L1 CPS>1 in 55 and >5 in 41 pts and HER2 positivity in 76 pts while 8 were negative (incl. one failed ISH). The 1° endpoint of 70% [email protected] was reached in arm B, but not in arm A (57%) (Table). Treatment related grade 3/4 AE/SAE occurred in 29/15 pts in arm B and in 20/17 pts in arm A. Liquid biopsy analyses showed strong correlation of high ctDNA load with shorter PFS/OS and emergence of truncating HER2 mutations on trast.Table: LBA54All (n=88)CPS>1 (n=55)CPS>5 (n=41)Arm AArm BArm AArm BArm AArm BORR32%56%38%65%29%68%mPFS3.2 mo10.7 mo2.2 mo11 mo2 mo11 mo[email protected]15%37%15%34%7%37%mDOR5.8 mo9.2 mo----mOS16.4 mo21.8 mo16.4 mo21.8 mo12.5 mo22.4 mo[email protected]57%70%54%70%51%69%mPFS – median PFS, [email protected] - PFS rate at 12 months, mDOR - duration of response, [email protected] - OS rate at 12 months, mo - months Open table in a new tab mPFS – median PFS, [email protected] - PFS rate at 12 months, mDOR - duration of response, [email protected] - OS rate at 12 months, mo - months Trast/nivo/FOLFOX showed increased efficacy compared to the ToGA regimen, whereas trast/nivo/ipi did not improve OS over trast/chemo. Subgroupanalyses are ongoing and will be presented.