788O - Association of pre-treatment ctDNA with disease recurrence and clinical and translational factors in patients with stage IIIB-D/IV melanoma treated with adjuvant immunotherapy (CheckMate 915)

Background

In patients (pts) with resectable melanoma, circulating tumor DNA (ctDNA) detection post-resection may be useful to inform disease state and recurrence risk.

Methods

Post-resection pre-treatment plasma from 1127 pts with stage IIIB-D/IV resected melanoma treated with nivolumab + ipilimumab vs nivolumab in the phase 3 CheckMate 915 study (NCT03068455) was retrospectively evaluated for ctDNA status and level, using a tumor-guided, pt-specific panel of up to 200 variants (Invitae Personalized Cancer MonitoringÔ). Kaplan-Meier and Cox regression models were used to evaluate the association between ctDNA status and recurrence-free survival (RFS), alone and combined with baseline clinical factors and biomarkers, including interferon-γ, TMB, tumor PD-L1, CD8+ T cells, tumor thickness, ulceration, and lymph node involvement.

Results

Overall pre-treatment ctDNA prevalence was ∼16% (95% CI: 14%–18%) and similar across most baseline demographics. A trend of greater ctDNA+ prevalence in higher stage III substages of melanoma was observed (IIIB = 11% [35/333], IIIC = 18% [110/596], IIID = 41% [13/32]). Pre-treatment ctDNA was associated with an increased risk of recurrence (HR 1.87, 95% CI: 1.48–2.36; Table). No significant interaction between ctDNA status and treatment arm was seen (ratio of hazard ratios: 0.99, 95% CI: 0.63–1.57). Patients with ctDNA present exhibited a greater rate of recurrence, seen as early as week 13 of therapy (Table). Distant metastasis-free survival results were similar. In composite analyses, improved RFS prediction was observed after combining ctDNA with clinical factors and biomarkers. Table: 788O

RFS probability by pre-treatment ctDNA status in CheckMate 915 treated patients

Conclusions

Pre-treatment ctDNA was associated with increased risk of early recurrence across treatment arms. ctDNA is a useful biomarker for combined analyses predicting outcome for adjuvant melanoma.

Clinical trial identification

NCT03068455.

Editorial acknowledgement

Professional medical writing and editorial assistance was provided by Emily Motola, PharmD, and Matthew Weddig, BA, of Spark Medica Inc, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

G.V. Long: Financial Interests, Personal, Advisory Board: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Merch Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Austr, Pierre Fabre, Provectus, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc. K. Desai: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. T. Tang: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. J.S. Weber: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Sponsor/Funding: Bristol Myers Squibb. S. Dolfi: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. C. Ritchings: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. S. Huang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M. Bolisetty: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. M. Sausen: Financial Interests, Institutional, Full or part-time Employment: Personal Genome Diagnostics; Financial Interests, Institutional, Stocks/Shares: Personal Genome Diagnostics. M. Del Vecchio: Non-Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Novartis, Merck Sharpe & Dohme; Non-Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Merck Sharpe & Dohme; Non-Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb, Novartis; Non-Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Novartis, Merck Sharpe & Dohme; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pierre Fabre. J. Larkin: Financial Interests, Personal, Research Grant: Achilles, Bristol Myers Squibb, MSD, Nektar, Novartis, Pfizer, Roche, Immunocore, Aveo, Pharmacyclics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, MSD, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, Aveo ; Financial Interests, Personal, Other, Honorariums, consultancy, speaker fee: Eisai, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honorariums, speaker fee: Novartis, Pfizer; Financial Interests, Personal, Other, Honorariums, Consultancy: Incyte; Financial Interests, Personal, Other, Honorariums: touchIME, touchEXPERTS, Royal College of Physicians, Cambridge Healthcare Research, RGCP, VJOncology, Agence Unik; Financial Interests, Personal, Other, Consultancy: iOnctura, Apple Tree, Debipharm; Financial Interests, Personal, Other, Speaker fee: Pierre Fabre, Ipsen, Roche, EUSA Pharma, Aptitude, AstraZeneca, GSK, Calithera, Ultimovacs, Seagen, eCancer, Inselgruppe, Goldman Sachs, MSD. J. Baden: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb, Johnson & Johnson. D. Balli: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. H. Chang: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb. J. Loffredo: Financial Interests, Institutional, Full or part-time Employment: Janssen; Financial Interests, Institutional, Stocks/Shares: Janssen. N. Zhang: Financial Interests, Institutional, Full or part-time Employment: Janssen; Financial Interests, Institutional, Stocks/Shares: Janssen. M. Wind-Rotolo: Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Agios Pharmaceuticals; Financial Interests, Institutional, Full or part-time Employment: Agios Pharmaceuticals. D. Tenney: Financial Interests, Institutional, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Institutional, Stocks/Shares: Bristol Myers Squibb.