Abstract 1226P
Background
Immune checkpoint inhibitors (ICI) are efficacious in subsets of OGA but predictive biomarkers beyond MMR and PD-L1 status are needed. Results from a phase II, multicentre, randomised, adaptive study (PLATFORM) showed that maintenance durvalumab (A3) did not prolong progression free or overall survival (PFS or OS) after platinum-fluoropyrimidine 1L CTx over surveillance (A1) in HER2 negative OGA. The Xerna™ TME RNA panel uses ≈100 genes to classify the TME along an immune and angiogenic axis into Angiogenic (A), Immune Active (IA), Immune Desert (ID) and Immune Suppressed (IS) phenotypes. We hypothesised that a high immune score (IA+IS) is predictive of ICI benefit compared to a low immune score (A+ID).
Methods
PD-L1 Combined Positive Score (CPS, SP263) and RNASeq were performed on FFPE archival biopsies from patients (pts) randomised to A1 and A3. Gene expression data was analysed using a machine learning artificial neural network algorithm to assign a TME subtype. Survival analyses (median follow-up: 39 months (m)) comparing IA+IS vs A+ID and CPS <5 vs ≥5 were conducted.
Results
TME data were available for 82 pts (A1: 38; A3: 44). 51.2% were IA+IS and 100% MMR proficient. 42.7% were CPS <5, 54.9% CPS ≥5 and 2.4% unknown. In A3, 6 and 12m PFS as well as 24m OS rates were higher in IA+IS vs A+ID (Table). Survival benefit was limited to the 12m PFS rate in A3 CPS ≥5 vs <5; no 6m PFS or 24m OS gain was seen. IA+IS showed a more pronounced treatment effect favouring A3 over A1 for both PFS and OS (PFS HR 0.64; OS HR 0.60) compared to A+ID (PFS HR 0.76; OS HR 0.84). A similar trend was observed in CPS ≥5 (PFS HR 0.61; OS HR 0.63) and <5 (PFS HR 0.72; OS HR 0.93). 36% (n=15/42) of IA+IS pts were CPS <5 compared to 53% (n=20/38) of A+ID pts. Table: 1226P
PFS and OS results
| Outcome | Xerna TME Panel | PD-L1 CPS | |||
| IA+IS | A+ID | <5 | ≥5 | ||
| n=22 | n=22 | n=17 | n=26 | ||
| A3 survival rates | 6m PFS | 35% | 27.3% | 31.3% | 28% |
| 12m PFS | 25% | 4.6% | 12.5% | 16% | |
| 24m OS | 35% | 22.7% | 31.3% | 24% | |
| HR (97.5% CI) | |||||
| n=42 | n=40 | n=35 | n=45 | ||
| A3 vs A1 | PFS | 0.64 (0.29 – 1.4) | 0.76 (0.36 – 1.57) | 0.72 (0.32 – 1.64) | 0.61 (0.29 – 1.27) |
| OS | 0.60 (0.26 – 1.37) | 0.84 (0.39 – 1.81) | 0.93 (0.40 – 2.18) | 0.63 (0.29 – 1.34) |
Conclusions
IA+IS phenotypes in HER2 negative OGA are indicative of improved survival with maintenance durvalumab compared to A+ID and may identify pts who benefit from ICI more consistently than CPS ≥5.
Clinical trial identification
NCT02678182.
Editorial acknowledgement
Legal entity responsible for the study
The Royal Marsden NHS Foundation Trust.
Funding
The Royal Marsden NHS Foundation Trust OncXerna Therapeutics, Inc. AstraZeneca.
Disclosure
C.Y.K. Fong: Financial Interests, Personal, Other, Chair and speaker at BMS I-O Academy Educational Meeting: Bristol Myers Squibb. S. Iyer: Financial Interests, Institutional, Full or part-time Employment: Oncxerna Therapeutics, Inc., Eli Lilly and Company; Financial Interests, Institutional, Stocks/Shares: Oncxerna Therapeutics, Inc., Eli Lilly and Company. L. Ausec: Financial Interests, Institutional, Full or part-time Employment: Genealis; Financial Interests, Institutional, Stocks/Shares: Genealis. A. Gregorc: Financial Interests, Institutional, Full or part-time Employment: Genealis; Financial Interests, Institutional, Stocks/Shares: Genealis. D. Pointing: Financial Interests, Institutional, Full or part-time Employment: Genealis, GBS Inc; Financial Interests, Institutional, Stocks/Shares: Genealis, Function Better Inc, GBS Inc; Financial Interests, Institutional, Advisory Role: Function Better Inc. L. Benjamin: Financial Interests, Institutional, Officer: Oncxerna Therapeutics, Inc.; Financial Interests, Institutional, Full or part-time Employment: Oncxerna Therapeutics, Inc.; Financial Interests, Institutional, Stocks/Shares: Oncxerna Therapeutics, Inc.; Financial Interests, Institutional, Leadership Role: Oncxerna Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. N. Starling: Financial Interests, Personal, Advisory Board: GSK, Novartis, MSD Oncology, Servier, AstraZeneca, Pfizer; Financial Interests, Personal, Invited Speaker: Clinical Options, Eli Lilly, Pierre Fabre, Amgen, Merck Serono; Financial Interests, Institutional, Research Grant, Sept 2017 (24m) Paid to institution research: Merck; Financial Interests, Institutional, Research Grant, Nov 2017 (48m) -Paid to institution research fund: AstraZeneca; Financial Interests, Institutional, Research Grant, Jan 2018 - Paid to institution research fund: Pfizer; Financial Interests, Institutional, Research Grant, July 2018 (36m) Paid to institution research fund: BMS. T.S. Waddell: Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb, Pfizer, Ipsen, Roche, Eisai; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel, accommodation, expenses: EUSA Pharma, Bristol Myers Squibb, Ipsen; Financial Interests, Personal, Advisory Role: Roche, Pfizer, Ipsen, Bristol Myers Squibb, Merck Sharp & Dohme, Eisai; Financial Interests, Personal, Invited Speaker: Pfizer, Ipsen, Bristol Myers Squibb, EUSA Pharma. R. Petty: Financial Interests, Personal, Advisory Board: BMS, Servier, Lilly, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, Servier, Pzfier, BMS; Financial Interests, Personal, Other, Funding to attend Congress: BMS; Financial Interests, Personal, Other, Funding to attend congress: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boston Biomedical, MSD, Clovis, Five Prime Therapeutics, Lilly, Merck Serano, Jansen, Roche, Amgen, Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Institutional, Product Samples: Lilly. M. Uhlik: Financial Interests, Institutional, Full or part-time Employment: Oncxerna Therapeutics, Inc., Hibercell, Inc.; Financial Interests, Institutional, Stocks/Shares: Oncxerna Therapeutics, Inc., Hibercell, Inc.; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company, Rigel Pharmaceuticals. I. Chau: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli-Lilly, MSD, Roche, Merck-Serono, AstraZeneca, OncXerna, Pierre Fabre, Boehinger Ingelheim, Astella, Incyte, GSK, Sotio, Daiichi-Sankyo, Eisai; Financial Interests, Personal, Other, DMC chairman: Five Prime Therapeutics; Financial Interests, Personal, Invited Speaker: Eisai, Eli-Lilly, Servier; Financial Interests, Institutional, Invited Speaker: Cilag-Janssen, Eli-Lilly. D. Cunningham: Financial Interests, Institutional, Research Grant: MedImmune/AZ, Clovis, Eli Lilly, 4SC, Bayer, Celgene, Leap, Roche; Non-Financial Interests, Advisory Role: OVIBIO. All other authors have declared no conflicts of interest.