Abstract 1092P
Background
The clinical utility of ctDNA-based approaches, such as bTMB and MR, to monitor and predict response during chemo-immunotherapy was evaluated using longitudinal cohort samples from a phase IIa study of patients (pts) with advanced sqNSCLC treated with 1L avelumab in combination with cetuximab and chemotherapy (NCT03717155).
Methods
Fifty-two plasma samples were obtained from 21 pts treated with 1L avelumab, cetuximab, gemcitabine, and cisplatin for 4 x 3-week cycles followed by avelumab and cetuximab maintenance. The confirmed best overall response (BOR) per RECIST v1.1 was available for 19 pts. The GuardantOMNI liquid biopsy (LBx) assay was used to detect somatic alterations in 497 genes and generate bTMB from baseline, and MR scores from baseline and day 85. bTMB and somatic alterations influencing response were explored. MR scores were calculated using the validated Guardant Response algorithm. Associations between ctDNA metrics and BOR were assessed.
Results
We detected somatic mutations in 51 of 52 samples. Biomarker-positive pts were defined as those with high bTMB score (≥20 mut/Mb) and/or STK11, KEAP1, LRP1B, ARID1A/1B/2 mutations. Ten of 18 baseline samples were biomarker-positive; all biomarker-positive pts had a BOR of partial response (PR) or stable disease (SD) and no progressive disease (PD). Eight of 18 baseline samples were biomarker-negative, of which 5 had a BOR of PR or SD and 3 had PD. All 3 pts with PD were TMB-low and 1 had a dual STK11/KRAS alteration, which was previously shown to negatively affect the clinical benefit of immunotherapy. The average ctDNA reduction at the tumor assessment visit following day 85 LBx collection for pts with PR/SD was significantly greater than for pts with PD (82% vs 57%; P=.032).
Conclusions
We showed that plasma ctDNA analysis supported MR assessment in pts treated with avelumab combination therapy, which could indicate its clinical utility as an adjunct to RECIST in monitoring tumor response. Plasma TMB-high combined with defined somatic mutations was associated with avelumab combination benefit. Prof. F. Ciardiello and Dr. Z. Feng are acknowledged as first authors and equal contributors to this abstract.
Clinical trial identification
NCT03717155.
Editorial acknowledgement
Editorial support was provided by Abhijith Thippeswamy of ClinicalThinking, and was funded by Merck (CrossRef Funder ID: 10.13039/100009945) as part of an alliance between Merck and Pfizer.
Legal entity responsible for the study
Merck, as part of an alliance between Merck and Pfizer.
Funding
Merck (CrossRef Funder ID: 10.13039/100009945), as part of an alliance between Merck and Pfizer.
Disclosure
F. Ciardiello: Financial Interests, Institutional, Research Grant: Merck, Amgen, Roche; Financial Interests, Personal, Advisory Role: Merck, Amgen, Roche, MSD, Pierre Fabre, Servier. Z. Feng: Financial Interests, Personal, Full or part-time Employment: Merck. N.R. Smith: Financial Interests, Personal, Other, Consultant: Merck. S. Shell: Financial Interests, Personal, Full or part-time Employment: Guardant Health; Financial Interests, Personal, Stocks/Shares: Guardant Health. A. Yablonovitch: Financial Interests, Personal, Full or part-time Employment: Guardant Health; Financial Interests, Personal, Stocks/Shares: Guardant Health. G. Guezel: Financial Interests, Personal, Full or part-time Employment: Merck. J. Scheuenpflug: Financial Interests, Personal, Full or part-time Employment: Merck. All other authors have declared no conflicts of interest.