74: Interim Results of a Phase II Trial of Regional Melphalan via Limb Infusion and Systemic PD1 Blockade in Patients with Extremity Sarcoma

Friday, March 24, 2023

1:01 PM – 1:13 PM

Location: Veterans Memorial Auditorium

Abstract Presenter(s)

Edmund Bartlett, MD

Assistant Attending, Gastric and Mixed Tumor Service
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure(s): Excite International Inc: Other (Terminated, January 3, 2022); SkylineDx: Research Grant (Ongoing)

First Author(s)

Edmund Bartlett, MD

Assistant Attending, Gastric and Mixed Tumor Service
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure(s): Excite International Inc: Other (Terminated, January 3, 2022); SkylineDx: Research Grant (Ongoing)

Author(s)

SD

Sandra D'Angelo, MD

Associate attending
Department of Medicine, United States

Disclosure information not submitted.
CK

Ciara Kelly, MD

Assistant Attending
Department of Medicine, United States

Disclosure information not submitted.
ER

Evan Rosenbaum, MD

Assistant Attending
Department of Medicine, United States

Disclosure information not submitted.
SM

Sujana Movva, MD

Assistant Attending
Department of Medicine, United States

Disclosure information not submitted.
JE

Joseph Erinjeri, MD

Attending
Department of Radiology, United States

Disclosure information not submitted.
CF

Charles Fisher, BA

Chief Anesthetist
Department of Anesthesia, United States

Disclosure information not submitted.
Samuel Singer, MD

Director MSK Sarcoma Center
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure information not submitted.
CA

Cristina Antonescu, MD, PhD

Attending
Department of Pathology, United States

Disclosure information not submitted.
Charlotte E. Ariyan, MD, PhD

Associate Attending, Gastric & Mixed Tumor Service
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure(s): Amgen Inc. and Merck & Co., Inc.: Consultant (Terminated); Iovance Biotherapeutics: Consultant (Ongoing); pfizer: Ownership Interest (Ongoing)

Disclosure(s):

Edmund Bartlett, MD: Excite International Inc: Other (Terminated, January 3, 2022); SkylineDx: Research Grant (Ongoing)

Charlotte E. Ariyan, MD, PhD: Amgen Inc. and Merck & Co., Inc.: Consultant (Terminated); Iovance Biotherapeutics: Consultant (Ongoing); pfizer: Ownership Interest (Ongoing)

Introduction: Checkpoint inhibition demonstrates modest activity in a limited number of select sarcoma subtypes. We undertook a phase II clinical trial to examine the efficacy of combining regional chemotherapy via isolated limb infusion (ILI) and concurrent systemic pembrolizumab in patients with locally advanced or metastatic extremity sarcoma.

Methods: In a single-center, single-arm phase II clinical trial (NCT04332874), patients with locally advanced or metastatic extremity sarcoma were treated with an initial dose of pembrolizumab (200mg), followed by ILI with melphalan and dactinomycin, and subsequent systemic pembrolizumab (once every 3 weeks) post-ILI (Figure). The primary objective is to estimate progression-free survival at 6-months by RECIST 1.1.

Results: To-date, nine patients have enrolled and been treated on protocol, including three patients with undifferentiated pleomorphic sarcoma, three with myxofibrosarcoma, one with angiosarcoma, one with clear cell sarcoma, and one with extra-axial chordoma. Five patients presented with unresectable or multifocal locoregional disease, the other four presented with advanced locoregional and distant metastases. At 6 months, 4 patients have ongoing partial responses to therapy: two with recurrent and multifocal regional myxofibrosarcoma; one with advanced primary extra-axial chordoma and lung metastases; and one with unresectable recurrent UPS and distant metastases, who experienced a complete pathologic response in the extremity. All patients had Weiberdink grade 1-2 (mild to moderate erythema/edema) following ILI. Immune-related toxicities include two cases of thyroiditis, and one patient who developed both diabetes, and adrenal insufficiency.

Conclusions: We report the early results of a phase II study of patients with extremity sarcoma treated with a combination of systemic pembrolizumab and isolated limb infusion. In the small number of patients treated to-date, promising responses have been observed and correlative studies are ongoing. Side effects have been manageable and are consistent with what would be anticipated from either therapy alone. Study enrollment is ongoing with a goal accrual of 30 patients.

Learning Objectives:

Understand the rational for the combination of isolated limb perfusion with systemic pembrolizumab in patients with extremity sarcoma
Describe the initial outcomes in sarcoma patients treated with isolated limb perfusion and systemic pembrolizumab
Describe the initial safety in sarcoma patients treated with isolated limb perfusion and systemic pembrolizumab