KEYNOTE-716: Phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma

Jason J Luke; Paolo A Ascierto; Matteo S Carlino; Jeffrey E Gershenwald; Jean-Jacques Grob; Axel Hauschild; John M Kirkwood; Georgina V Long; Peter Mohr; Caroline Robert; Merrick Ross; Richard A Scolyer; Charles H Yoon; Andrew Poklepovic; Piotr Rutkowski; James R Anderson; Sama Ahsan; Nageatte Ibrahim; Alexander M M Eggermont

doi:10.2217/fon-2019-0666

KEYNOTE-716: Phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma

Future Oncol. 2020 Jan;16(3):4429-4438. doi: 10.2217/fon-2019-0666. Epub 2019 Dec 24.

Authors

Jason J Luke¹, Paolo A Ascierto², Matteo S Carlino^{3

4

5

6}, Jeffrey E Gershenwald⁷, Jean-Jacques Grob⁸, Axel Hauschild⁹, John M Kirkwood¹, Georgina V Long^{5

6

10

11}, Peter Mohr¹², Caroline Robert^{13

14}, Merrick Ross⁷, Richard A Scolyer^{5

6

15}, Charles H Yoon¹⁶, Andrew Poklepovic¹⁷, Piotr Rutkowski¹⁸, James R Anderson¹⁹, Sama Ahsan¹⁹, Nageatte Ibrahim¹⁹, Alexander M M Eggermont^{13

20}

Affiliations

¹ Cancer Immunotherapeutics Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA.
² Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
³ Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.
⁴ Blacktown Cancer and Haematology Centre, Blacktown Hospital, Blacktown, NSW, Australia.
⁵ Melanoma Institute Australia, Sydney, NSW, Australia.
⁶ Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
⁷ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁸ Department of Dermatology and Skin Cancers, Hôpital de la Timone, Aix-Marseille Université, Marseille, France.
⁹ Department of Dermatological Oncology, University Hospital Schleswig-Holstein, Kiel, Germany.
¹⁰ Department of Medical Oncology, Mater Hospital, North Sydney, NSW, Australia.
¹¹ Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia.
¹² Department of Dermatology, Elbe Kliniken Buxtehude, Buxtehude, Germany.
¹³ Dermatology Unit, Department of Oncology, Gustave Roussy Cancer Centre, Villejuif, France.
¹⁴ Department of Medicine, Université Paris-Sud, Orsay, France.
¹⁵ Department of Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
¹⁶ Department of Surgical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹⁷ Department of Internal Medicine, VCU Massey Cancer Center, Richmond, VA 23298, USA.
¹⁸ Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
¹⁹ Department of Clinical Oncology, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
²⁰ Department of Medical Oncology, Gustave Roussy Cancer Institute & Université Paris-Saclay, Paris, France.

PMID: 31870188
DOI: 10.2217/fon-2019-0666

Abstract

Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant metastases are limited. Although adjuvant IFN-α2b is associated with improved relapse-free survival in patients with high-risk melanoma, toxicity and limited overall survival benefits limit its use. Adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved recurrence-free survival, compared with placebo, in patients with resected stage III melanoma in the Phase III KEYNOTE-054 trial; efficacy in patients with stage II disease has not been established. This article describes the design and rationale of KEYNOTE-716 (NCT03553836), a two-part, randomized, placebo-controlled, multicenter Phase III study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Clinical trial registry & ID: ClinicalTrials.gov, NCT03553836.

Keywords: adjuvant therapy; high-risk stage II melanoma; immune checkpoint inhibitor; pembrolizumab.

Publication types

Clinical Trial Protocol

MeSH terms

Adolescent
Adult
Antibodies, Monoclonal, Humanized / administration & dosage*
Antibodies, Monoclonal, Humanized / adverse effects
Antineoplastic Agents, Immunological / administration & dosage*
Antineoplastic Agents, Immunological / adverse effects
Chemotherapy, Adjuvant / methods
Child
Clinical Trials, Phase III as Topic
Cross-Over Studies
Dermatologic Surgical Procedures
Disease-Free Survival
Female
Humans
Male
Melanoma / immunology
Melanoma / mortality
Melanoma / pathology
Melanoma / therapy*
Multicenter Studies as Topic
Neoplasm Recurrence, Local / epidemiology*
Neoplasm Recurrence, Local / prevention & control
Neoplasm Staging
Placebos / administration & dosage
Placebos / adverse effects
Programmed Cell Death 1 Receptor / antagonists & inhibitors
Programmed Cell Death 1 Receptor / immunology
Randomized Controlled Trials as Topic
Skin Neoplasms / immunology
Skin Neoplasms / mortality
Skin Neoplasms / pathology
Skin Neoplasms / therapy*
Young Adult

Substances

Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
PDCD1 protein, human
Placebos
Programmed Cell Death 1 Receptor
pembrolizumab

Associated data

ClinicalTrials.gov/NCT03553836