LBA48 - Pathologic response and exploratory analyses of neoadjuvant-adjuvant versus adjuvant pembrolizumab (PEM) for resectable stage IIIb-IV melanoma from SWOG S1801

Background

Primary efficacy results from SWOG S1801 showed an improved event-free survival (EFS) in patients who received neoadjuvant-adjuvant (NAT) PEM compared to adjuvant (AT) PEM. In pooled analyses and smaller neoadjuvant studies, pathologic response has been suggested as an important surrogate marker of clinical outcome.

Methods

S1801 was a randomized phase II trial for clinically detectable, resectable AJCC 8th edition stage IIIB-IV melanoma. Participants were randomized 1:1 to AT PEM (surgery then 18 doses of PEM q3w) or NAT PEM (3 doses pre-operative PEM, surgery, 15 doses PEM q3w). Sites submitted surgical specimens for central review. For determination of pathologic response to NAT, these specimens were assessed for percentage of necrosis and viable tumor by a single pathologist blind to the clinical results.

Results

As of August 31, 2023, 281 participants had surgery (138 NAT, 143 AT). Of those randomized to NAT, 109 specimens were reviewed for pathologic response, 89 were lymph node specimens. Pathologic response and recurrence-free survival (RFS) outcomes for these lymph node specimens are shown in the table. 130 of 138 NAT participants who underwent surgery had RECIST response data; 15 (12%) achieved complete response (CR), 50 (38%) partial response (PR) for an overall response rate of 50%; 50 (38%) experienced stable disease (SD), and 15 (12%) progression of disease (PD). Table: LBA48

¹RFS measured from date of surgery

Conclusions

The use of NAT with single-agent PEM in resectable stage IIIB-IV melanoma results in a 51% major pathologic response rate (pCR + pnCR) with 40% pathologic complete responses. 2-year RFS rates are highest in those achieving pathologic or radiographic response.

Clinical trial identification

NCT03698019.

Editorial acknowledgement

Legal entity responsible for the study

SWOG.

Funding

SWOG, Merck Sharp & Dohme.

Disclosure

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. C.D. Lao: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Institutional, Local PI, Research funding: BMS, Novartis, Genentech, Oncosec. A. Hegde: Financial Interests, Institutional, Local PI: BeiGene, Jounce Therapeutics, Cytomx Therapeutics, Calithera Biosciences Inc, AstraZeneca Pharmaceuticals LP, Arcus Biosciences Inc, Takeda Pharmaceuticals Company Ltd, AbbVie Inc. E. Buchbinder: Financial Interests, Personal, Advisory Board: Instilbio, Nektar, Novartis, BMS, Iovance, Merck, Sanofi, Xilio; Financial Interests, Institutional, Coordinating PI: Genentech, Partners therapeutics; Other, Spouse employment: AstraZeneca, Takeda. V.K. Sondak: Financial Interests, Personal, Advisory Board: Merck, Bristol Myers Squibb, Iovance, OncoSec, Regeneron, Ultimovacs; Financial Interests, Personal, Other, Independent Data Safety Monitoring Committee: Alkermes, Novartis; Financial Interests, Personal, Other, Independent medical monitor for clinical trial: Genesis Drug Discovery & Development; Financial Interests, Institutional, Research Grant, Research grant to institution: Turnstone Biologics; Financial Interests, Institutional, Coordinating PI, Per patient funding to institution to support clinical trial: Skyline DX; Financial Interests, Institutional, Local PI, Research grant to institution: Neogene Therapeutics. A. Ribas: Financial Interests, Personal, Advisory Board, Honoraria for consulting: Amgen, Astra-Zeneca, Merck, Novartis, Jazz; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: Apricity, Appia, Arcus, Compugen, Immpact, Lutris, MapKure, Merus, PACT Pharma, Synthekine, Tango; Financial Interests, Personal, Member of Board of Directors, Member of the Board of Directors: Arcus, Lutris, PACT Pharma; Financial Interests, Personal, Stocks/Shares, Stock ownership: 4C Biomed, Apricity, Appia, Arcus, Compugen, Highlight, ImaginAb, Immpact, Immunesensor, Inspirna, Isoplexis, Lutris, MapKure, Merus, Pluto, Synthekine, PACT Pharma, Tango, Advaxis, CytomX, RAPT, Kite-Gilead; Financial Interests, Personal, Advisory Board: Arsenal Bio; Financial Interests, Institutional, Funding: Agilent, Bristol-Myers Squibb; Non-Financial Interests, Advisory Role, Member of the scientific advisory board: Highlight, Immunesensor, Inspirna, Pluto. V. Prieto: Financial Interests, Personal, Other, Consultant: Orlucent, Merck, Castle Biosciencies, Novartis. All other authors have declared no conflicts of interest.