1094P - Relapse free survival (RFS) at 3 years by pathological (path) response to neoadjuvant systemic treatment (NST) in patients (pts) with surgically resectable, high-risk melanoma

Background

For pts with high-risk, surgically resectable melanoma, NST demonstrated improved outcomes compared to upfront surgery and adjuvant therapy. Outcomes are most improved in pts who achieve a pathologic complete response (pCR) with any NST [targeted therapy (TT) or immune checkpoint blocked (ICB)]. Prior studies in ICB NST suggest improved outcomes associated with any path response. We evaluated updated data from 2 previously reported NST studies for long-term outcomes by path response, determined by percent tumor viability (TV).

Methods

We analyzed 2 trials in for clinical stage III/IV, resectable melanoma: NST [2 months (mo)] + adjuvant (10 mo) dabrafenib + trametinib (DT) (NCT02231775) and ICB, (NCT02519322). ICB trial arms were 8-9 wks of NST: nivolumab (nivo) (Arm A), ipilimumab 3mg/kg plus nivo 1mg/kg (Arm B) both followed by adjuvant nivo for 6 mo, and nivo + relatlimab (2 mos NST, 10 mos adjuvant) (Arm C). RFS was estimated using Kaplan Meier (KM) method and differences by path responses were evaluated by the log-rank test.

Results

97 pts of 103 treated pts underwent surgery and were evaluable for analysis by detailed path response: 49 pts on DT and 48 on ICB (11 Arm A, 10 Arm B, 28 Arm C). Median follow up for all pts was 34.5 mos (3.8-94.8). Median RFS in mos for any pt with pCR was not reached and 23.7 mos (95% CI: 11.3, 30.5) for pts with 50% TV (pNR), 11-50% TV (pPR), 1 - ≤10% TV near pCR, and 0% TV pCR. Additional clinical data and outcomes will be reported at the meeting. Table: 1094P

36 mos RFS KM rates

Conclusions

At 3 years, RFS in pts treated with NST TT and ICB with pCR continues to be superior to those with

Clinical trial identification

NCT02231775 and NCT02519322.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Novartis, BMS, MRA/Rising Tide Fondation.

Disclosure

I.C. Glitza: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Array, Novartis, Sintetica; Financial Interests, Institutional, Research Funding: BMS, Merck, Pfizer. M.I. Ross: Financial Interests, Institutional, Research Funding: Amgen; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Castle Biosciences, Merck, Novartis. J.E. Gershenwald: Financial Interests, Personal, Other, consultant, advisory board, scientific advisory board: Merck; Financial Interests, Personal, Other, consultant: Regeneron; Financial Interests, Personal, Royalties, author/coauthor of several chapters for this online clinical resource: UpToDate. J. Mcquade: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, BMS, Roche. M. Wong: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Pfizer, BMS, Regeneron, EMD Serono, ExiCure, Castle Biosciences. S. Patel: Financial Interests, Personal, Advisory Board: TriSalus, Cardinal Health, Castle Biosciences, Novartis, BMS, Pfizer, Immatics; Financial Interests, Personal, Other, Consultant for educational materials: Advance Knowledge in Healthcare; Financial Interests, Personal, Advisory Board, Advisory Board and Corporate Day speaker (unbranded): Delcath; Financial Interests, Personal, Other, Independent Data Monitoring Committee: Immunocore; Financial Interests, Personal, Other, Consultant: Guidepoint Global; Financial Interests, Institutional, Trial Chair: Provectus Biopharmaceuticals, Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Lyvgen, InxMed, Foghorn Therapeutics, IDEAYA, Novartis, Seagen, Syntrix Bio; Financial Interests, Institutional, Steering Committee Member: TriSalus Life Sciences; Non-Financial Interests, Member: ASCO, AACR, International Society of Ocular Oncology, Society for Melanoma Research; Non-Financial Interests, Leadership Role: SWOG. A. Diab: Financial Interests, Institutional, Research Funding: BMS. M. Postow: Financial Interests, Personal, Advisory Board: BMS, Chugai, Merck, Nektar, Pfizer; Financial Interests, Institutional, Coordinating PI: BMS; Financial Interests, Institutional, Local PI: Merck, Novartis. C.E. Ariyan: Financial Interests, Personal, Advisory Board: Merck, Iovance; Financial Interests, Personal, Stocks/Shares: Pfizer. V. Prieto: Financial Interests, Personal, Other, Consultant: Orlucent, Merck, Castle Biosciences, Novartis. M. Davies: Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, BMS, Sanofi-Aventis, GSK, Vaccinex, Apexigen, Eisai, Iovance, Merck, ABM Therapeutics; Financial Interests, Institutional, Coordinating PI: Pfizer; Financial Interests, Institutional, Research Grant: ABM Therapeutics, Lead Pharma, Genentech, GSK, Sanofi-Aventis, Merck, Oncothyreon; Financial Interests, Research Grant: Myriad. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer, Jazz Pharmaceuticals; Financial Interests, Institutional, Trial Chair: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Merck, RAPT Pharmaceuticals; Financial Interests, Institutional, Steering Committee Member: Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. J. Wargo: Financial Interests, Personal, Invited Speaker: Dava Oncology, Omniprex, Illumina, Gilead, PeerView, Physician Education Resource, MedImmune, Exelixis, Bristol Meyers Squibb, Medscape; Financial Interests, Personal, Advisory Board: Roche Genentech, Novartis, AstraZeneca, GSK, Merck; Financial Interests, Personal, Stocks/Shares: Micronoma, OSE therapeutics; Other, J.A.W. is an inventor on a US patent application (PCT/US17/53.717) submitted by the University of Texas MD Anderson Cancer Center which covers methods to enhance immune checkpoint blockade responses by modulating the microbiome: University of Texas MD Anderson Cancer Center. R. Amaria: Financial Interests, Personal, Advisory Board: Iovance Biotherapeutics, Novartis, Erasca; Financial Interests, Institutional, Coordinating PI: Merck, Bristol Myers Squibb, Novartis; Financial Interests, Institutional, Local PI: Iovance, Roche; Financial Interests, Institutional, Trial Chair: Obsidian. All other authors have declared no conflicts of interest.