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 (OSR@12) 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% OSR@12 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: LBA54
|All (n=88)||CPS>1 (n=55)||CPS>5 (n=41)|
|Arm A||Arm B||Arm A||Arm B||Arm A||Arm B|
|mPFS||3.2 mo||10.7 mo||2.2 mo||11 mo||2 mo||11 mo|
|mDOR||5.8 mo||9.2 mo||-||-||-||-|
|mOS||16.4 mo||21.8 mo||16.4 mo||21.8 mo||12.5 mo||22.4 mo|
mPFS – median PFS, PFSR@12 - PFS rate at 12 months, mDOR - duration of response, OSR@12 - 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.
Clinical trial identification
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A. Stein: Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Advisory Board: BMS. All other authors have declared no conflicts of interest.