703P - Prognostic scores for immunotherapy-based phase one trials (P1T): To GRIm or not to GRIm?

Background

Prognostic scores are useful to better select patients (pts) who may benefit from P1T. The Royal Marsden Hospital (RMH) score (Lactate deshydrogenase (LDH), albumin, number of metastatic sites) was the first validated prognostic score in the area of chemotherapy and targeted agents (TA) P1T. More recently, GRIm-Score (LDH, albumin, neutrophil-to-lymphocyte ratio) was shown as a better prognostic score for patients treated with immune-checkpoint therapies. We aimed to compare RMH and GRIm scores in the area of new immunotherapy (IT) agents P1T, monotherapy or in combination.

Methods

We performed a retrospective analysis of adult pts enrolled into P1T evaluating at least one IT at the Centre Léon Bérard, between 2012 and 2022. Univariate and multivariate analyses were conducted to assess the prognostic value of RMH and GRIm scores at screening for overall survival (OS) and progression-free survival (PFS).

Results

We identified 411 pts from 36 P1T, of whom 119 (29.0%) received IT monotherapy, 240 (58.4%) bi-IT, 49 (11.9%) IT monotherapy associated with TA and 3 (0.7%) IT triplet. The median age was 62 years [20 - 83] and the median number of previous lines was 2 [0 - 11]. The most common tumor types were colorectal (n=69), pancreatic (n=52), breast, (n=45), lung cancers (n=45), melanoma (n=31) and urothelial carcinomas (n=27). The median OS was 8.8 months [95%CI 7.7 – 10.0] and the median PFS, based on iRECIST criteria, was 2.2 months [95%CI 2.0 – 2.7]. At screening, 77.1% of patients (n=317) had a favorable RMH score (<2) and 81.5% (n=326) had a favorable GRIm-score (<2), with a discordance of 14.8% between both scores. In multivariate analyses, a favorable GRIm-score was associated with better OS (HR 0.47 [95% CI 0.34-0.65, p < 0.001), together with Performans Status (PS) 0 vs 1 (HR 0.76 [95% CI 0.59-0.99], p = 0.039) whereas RMH was not (HR 0.75, 95%CI [0.53-1.05], p = 0.091). Similarly, GRIm-score and PS were associated with better PFS, with respective HR 0.65 [95%CI 0.50 – 0.85], p = 0.002 and 0.66 [95% CI 0.53-0.82], p < 0.001, contrary to RMH.

Conclusions

While our results confirm RMH as suboptimal to determine the prognosis of patients included in P1T trials evaluating IT, GRIm-score and PS at screening both appear as highly reliable prognostic factors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Corbaux: Financial Interests, Institutional, Local PI: Sensorion. L. Verlingue: Financial Interests, Personal, Stocks/Shares, CEO of Resolved dedicated to treatment approval prediction: Resolved; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Contract for bioinformatic analysis: Pierre Fabre, Servier; Non-Financial Interests, Advisory Role: Klineo; Non-Financial Interests, Institutional, Proprietary Information, As part of the Drug Development Department (DITEP) of Gustave Roussy and of the Phase 1 unit of Centre Léon Bérard, as medical doctor, LV report being: Principal/sub-Investigator of Clinical Trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd., Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd., Forma Tharapeutics, Gamamabs, Genentech, GSK, H3 Biomedicine, F. Hoffmann-La Roche AG, Imcheck Therapeutics, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma A: Pharmas. M. Brahmi: Financial Interests, Personal, Invited Speaker, Invited speaker in a local meeting on GIST treatment in 2019: Bayer; Financial Interests, Personal, Invited Speaker, Invited speaker in a local meeting on immunotherapy: Amgen. A. Swalduz: Financial Interests, Personal, Advisory Board: Roche, AZD, BMS, MSD, Takeda, Pfizer, Amgen, Boehringer; Financial Interests, Personal, Other, Travel: Pfizer, Roche. C. Terret: Financial Interests, Institutional, Invited Speaker, Local Symposium on RE+ HER2-Breast cancer in older women: treatment innovation and perspective: Lilly. P. Cassier: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Roche, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Other, Advisor: OSE Immunotherapeutics; Financial Interests, Institutional, Local PI: AbbVie, Blueprint, Boehringer Ingelheim, Bristol Myers Squibb, Exelixis, GSK, Incyte, Janssen, Loxo/Eli Lilly, Novartis, Roche, Taiho, Toray Industries; Financial Interests, Institutional, Coordinating PI: Amgen, Transgene; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. A. Vinceneux: Financial Interests, Personal, Invited Speaker: Pfizer, Astellas, BMS; Financial Interests, Institutional, Coordinating PI: Loxo Lilly, BioNTech, Emergence Therapeutics; Financial Interests, Institutional, Local PI: Janssen, Roche, AstraZeneca, Ipsen, Exelixis, Exscienta, Kinnate. All other authors have declared no conflicts of interest.