136P - Circulating hPG80 (WNT pathway activation) as a potential new prognostic/predictive factor of immunotherapy (ICI) efficacy: ONCOPRO prospective study

Background

There is an unmet need for predictors of immune checkpoint inhibitor (ICI) efficacy. WNT/β-catenin signaling activation is associated with immunosuppression. hPG80 is released from cancer cells to blood due to WNT pathway activation in multiple cancers (You et al, eBioMedicine 2020). ONCOPRO (NCT03787056) was a large prospective case-control study, where hPG80 blood titers were measured in 421 patients with 16 different cancers. Here, the prognostic/predictive values of hPG80 concentrations at different timepoints were assessed in 3 metastatic cancers usually treated with ICI (lung NSCLC, kidney RCC, Head and Neck H&N).

Methods

Of 421 ONCOPRO patients, 45 had NSCLC (treated with 1^st line ICI/any line ICI: 47%/80%); 24 RCC (72%/84%); 20 H&N cancers (35%/90%). The prognostic/predictive values of blood hPG80 levels measured with ELISA DxPG80.lab kit (< or ≥ median) at baseline, and at each treatment cycle, were explored for median PFS/OS (mPFS/mOS), and hazard-ratio (HR) [95% CI].

Results

No prognostic value of baseline hPG80 level at diagnosis was found. However, a low hPG80 titer (< median, vs ≥ median) after 2 cycles of the 1^st line treatment (with ICI or not) was associated with a trend for better PFS/OS in NSCLC (mPFS, NR vs 5.9 mo, HR = 0.46 [0.19-1.08]; mOS, NR vs 19.3 mo, HR = 0.28 [0.09-0.91]); in RCC (mPFS, NR vs 5.9 mo, HR= 0.25 [0.05-1.21]; OS, immature); and in ICI treated H&N (OS, HR = 0.55 [0.10-3.01]), suggesting hPG80 prognostic value. The potential predictive value for ICI efficacy was explored. In patients treated without 1^st line ICI (53% of NSCLC, 65% of H&N), hPG80 after 2 cycles was not associated with PFS (NSCLC, HR = 0.96 [0.26-3.59]; H&N: HR = 1.58 [0.26-9.52]). However, in patients treated by 1^st line ICI (47% of NSCLC; 72% of RCC), it was associated with a clinically better PFS (NSCLC: mPFS, NR vs 6.6 mo, HR = 0.11 [0.01-0.89]; RCC, mPFS, NR vs 6.2 mo, HR = 0.46 [0.09-2.39]).

Conclusions

ONCOPRO prospective study suggests that blood levels of hPG80 after 2 cycles of ICI-based treatment (as an indicator of WNT/β-catenin activation change) may be a potential prognostic and clinically relevant predictive factor of the benefit from ICI in different solid cancers, warranting further development.

Clinical trial identification

NCT03787056; Sponsor Lyon University Hospital (Hospices Civils de Lyon) Information provided by Lyon University Hospital (Hospices Civils de Lyon, Responsible Party) Last Update Posted 2021-07-16.

Editorial acknowledgement

Legal entity responsible for the study

Lyon University Hospital.

Funding

Biodena Care.

Disclosure

B. You: Financial Interests, Personal, Advisory Role: Consulting for MSD, AstraZeneca, GSK-Tesaro, Bayer, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad, Menarini, Gilead, EISAI, Pharma&.. B. Vire: Financial Interests, Personal, Full or part-time Employment: BiodenaCare. All other authors have declared no conflicts of interest.