BP1. Neoadjuvant Pembrolizumab in Stage IIB/C Melanoma: Updated Clinical Outcomes and Translational Data from Phase 2 Trial NCT03757689

Friday, March 6, 2026

8:02 AM - 8:09 AM MST

Location: 301A

Co-Author(s)

AL

Anthony Lee, BS

University of Pennsylvania
Philadelphia, Pennsylvania, United States
GW

Guanning Wang, PhD

University of Pennsylvania
Philadelphia, Pennsylvania, United States
SM

Sheryl Mitnick, MPH, BSN (she/her/hers)

Program Manager
University of Pennsylvania
Philadelphia, Pennsylvania, United States
PG

Phyllis Gimotty, PhD

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania
Philadelphia, Pennsylvania, United States
Gracia M. Vargas, MD

Resident
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Russell A. Simons, MD, MPH

Resident
Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
John T. Miura, MD

Assistant Professor of Surgery
Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
TM

Tara C. Mitchell, MD

Hematologist oncologist
Division of Hematology-Oncology, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
RA

Ravi K. Amaravadi, MD

Division of Hematology-Oncology, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
LS

Lynn M. Schuchter, MD

Division of Hematology-Oncology, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
XX

Xiaowei Xu, MD, PhD

Professor of Pathology and Laboratory Medicine
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
MD

Michael A. Davies, MD, PhD

Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
RA

Rodabe N. Amaria, MD

Melanoma Medical Oncology
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center
Houston, Pennsylvania, United States
JC

Jason A. Chesney, MD, PhD

Professor of Medicine
Division of Medical Oncology and Hematology, University of Louisville
Louisville, Kentucky, United States
Roi Weiser, MD

Assistant Professor
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Jeffrey E. Gershenwald, MD (he/him/his)

Professor
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
KM

Kelly M. McMasters, MD, PhD (he/him/his)

Ben A. Reid, Sr., MD Professor and Chair
Department of Surgery, University of Louisville
Louisville, Kentucky, United States
AH

Alexander C. Huang, MD

Assistant Professor
Division of Hematology-Oncology, Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
GK

Giorgos C. Karakousis, MD (he/him/his)

Professor of Surgery
Department of Surgery, University of Pennsylvania Health System, United States

Primary Presenter(s)

M. Saad Farooq, MD, MSTR

General Surgery Resident
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States

Slides

Introduction: Clinical stage IIB/C melanoma is a high-risk subset with outcomes comparable to stage IIIA/B disease. Herein we report updated clinical outcomes from NCT03757689, the first trial to assess neoadjuvant pembrolizumab (pembro) in clinical stage IIB/C melanoma. Additionally, we report preliminary translational data leveraging biospecimens from trial patients (pts).

Methods: In this investigator-initiated phase 2 multicenter single-arm trial, pts with clinical stage IIB/C melanoma (n=63) received a single dose of neoadjuvant pembro 3 weeks (wks) prior to wide excision (WE) and sentinel lymph node (SLN) biopsy, followed by adjuvant pembro every 3 wks for up to 1 year (y). Recurrence-free (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analysis was used to identify factors associated with recurrence. The NanoString platform was used to analyze bulk gene expression from SLNs of trial pts (n=39). Peripheral blood was immunophenotyped using spectral flow cytometry (n=10).

Results: Of 63 evaluable pts, 11 (17%) experienced a recurrence at the latest follow-up (median follow-up time: 27 months). Estimated 3-y RFS was 79% overall (IIB: 86%, IIC: 73%), with a median time-to-recurrence of 10.7 months. 3-y OS was 85% overall (IIB: 88%, IIC: 84%).
In pts with residual primary tumor at the time of WE (n=28), 3-y RFS was 66% vs 91% for those without residual tumor (n=35; log-rank p=0.015). On multivariable analysis, presence of residual tumor was significantly associated with recurrence (adjusted hazard ratio: 6.39, p=0.032).
On flow cytometric analysis of peripheral blood, proliferation of exhausted CD8 T cell populations significantly increased 3-wks after a single dose of neoadjuvant pembro (PD1⁺CD39⁺Ki67⁺: 10.8% pre vs 22.0% post, p< 0.001). Additionally, melanoma-specific CD8 T cells targeting MART-1 and gp100 were identified using combinatorial tetramers.
Gene expression analysis of the SLN showed significant relative increases in genes associated with immune activation (GZMA, CXCL9) and exhaustion (LAG3, TIGIT) in SLN- pts (n=25) vs stage I controls (n=9; p< 0.05). In SLN+ pts (n=14), genes associated with immune activation (CXCL9), immunoregulation (IL2RA), exhaustion (LAG3, TIGIT), and melanoma (DCT, TYR, MLANA) demonstrated increased expression (p< 0.05).

Conclusions: In this updated analysis of NCT03757689, clinical stage IIB/C melanoma pts receiving neoadjuvant pembro exhibited favorable RFS/OS, along with significant immunologic changes in the systemic circulation and SLN.

Learning Objectives:

Assess clinical efficacy of neoadjuvant pembrolizumab in clinical stage IIB/C melanoma with regards to recurrence-free and overall survival.
Characterize immunologic changes in the systemic circulation and sentinel lymph node of trial patients from flow cytometry and gene expression analysis.
Understand factors associated with recurrence in this patient population.