SARC028: A Phase II Study of the Anti-PD1 Antibody Pembrolizumab (MK-3475) in Patients With Advanced Sarcomas

NCT02301039 | Completed Phase 2 Results DMC

• 1 other identifier: SARC028
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to determine the efficacy of pembrolizumab in patients with advanced sarcomas.

Conditions

Soft Tissue Sarcoma; Bone Sarcoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The Objective Response Rate (ORR) is the percentage of patient's tumor that shrinks or disappears after treatment. ORR will be evaluated according to RECIST (Response Evaluation Criteria In Solid Tumors) 1.1, whereby Complete Response is defined as the disappearance of all target lesions and Partial Response is defined as at least a 30% decrease in the sum of the diameters of target lesions in reference to the baseline diameters. Overall Response (OR) = CR + PR.

  Assessments will be conducted at 8 weeks, up to 5 years

Secondary Outcomes (4)

• Adverse Events Related to Pembrolizumab Treatment in Patients With Advanced Sarcoma, by Patient

  Up to 5 years

• The Progression-free Survival (PFS)

  up to 5 yrs

• Response Rate by Immune-related Response Criteria (Ir-RC)

  Assessment at 8 weeks, up to 5 years

• Overall Survival (OS)

  up to 5 years

Study Arms (3)

Soft tissue sarcoma

EXPERIMENTAL

Patients with the following types of soft tissue sarcoma: leiomyosarcoma, poorly differentiated/de-differentiated liposarcoma, high grade pleomorphic undifferentiated sarcoma/MFH, MPNST and synovial sarcoma). Pembrolizumab will be administered at 200 mg intravenously every 3 weeks

Drug: Pembrolizumab

Bone sarcoma

EXPERIMENTAL

Patients with the following types of bone sarcoma: Ewing sarcoma, osteosarcoma, and chondrosarcoma \[de-differentiated or mesenchymal\]. Pembrolizumab will be administered at 200 mg intravenously every 3 weeks

Drug: Pembrolizumab

Expansion

EXPERIMENTAL

Patients with the following types of soft tissue sarcoma: poorly differentiated/de-differentiated liposarcoma, high grade pleomorphic undifferentiated sarcoma. Pembrolizumab was administered at 200 mg intravenously every 3 weeks

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Also known as: Mk-3475

Bone sarcoma; Expansion; Soft tissue sarcoma

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years (Age ≥ 12 years for patients with bone sarcomas).
• Histologically confirmed diagnosis of unresectable, recurrent, and/or metastatic high grade soft-tissue or bone sarcoma of one of the following subtypes: soft tissue sarcomas (leiomyosarcoma, poorly differentiated/de-differentiated liposarcoma, high grade pleomorphic undifferentiated sarcoma/MFH and synovial sarcoma), and bone sarcomas (Ewing sarcoma, osteosarcoma, and chondrosarcoma \[de-differentiated or mesenchymal\]).
• ECOG Performance Status of 0 or 1.
• At least one site of measurable disease on CT/MRI scans as defined by RECIST 1.1. Baseline imaging must be performed within 30 days of dosing.
• At least one site of accessible disease for pre- and post-treatment core biopsies for at least 20 patients per arm on the expansion cohorts.
• Patients may have received 1-3 prior systemic therapies in the metastatic setting.
• Adequate organ function within 14 days of dosing
• Must be willing to provide and have available archival tissue for PD-L1 testing.
• Written, voluntary informed consent.
• Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 120 days after last study drug administration. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study.
• Effective methods of birth control include: surgically sterile, barrier device (condom, diaphragm), contraceptive coil, intrauterine device (IUD), and abstinence.
• Life expectancy of \>12 weeks.
• Patients with central nervous system disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression for at least 4 weeks prior to screening, have no evidence of new or enlarging brain metastases, and are off steroids for at least 7 days before first dose of pembrolizumab.

You may not qualify if:

• Prior systemic therapy targeting PD-1: PD-L1 axis.
• Patients who are curable by conventional multidisciplinary management.
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
• Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation \< 2 weeks prior to screening or who have not recovered adequately from side effects of such therapy.
• Patients who have active infections requiring therapy.
• Patients that are known to be positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive), or Hepatitis C (HCV RNA \[qualitative\] is detected); patients with negative Hepatitis C antibody testing may not need RNA testing.
• Patients that have a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial.
• Patients who received systemic anti-cancer treatment prior to the first dose of study drug within the following time frames:
• Patients with active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Patients that require inhaled steroids or local steroid injections would not be excluded from the study. Patients with hypothyroidism not from autoimmune disease that is stable on hormone replacement will not be excluded from the study.
• Women who are pregnant or nursing/breastfeeding.
• Known hypersensitivity to pembrolizumab or another mAb.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Patients with untreated central nervous system disease. Patients with controlled treated CNS lesions who have undergone surgery or stereotactic radiosurgery and stable for 4 weeks are eligible.
• Inability to comply with protocol required procedures.
• Patients with medical conditions that require chronic systemic corticosteroid therapy or require any other form of immunosuppressive medication. However, patients using physiologic replacement doses of hydrocortisone, or its equivalent, will be considered eligible for this study: up to 20 mg hydrocortisone (or 5 mg of prednisone) in the morning and 10 mg hydrocortisone (or 2.5 mg prednisone) in the evening.

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

University of Southern California

Los Angeles, California, 90033, United States

Location

Medstar Health Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Oregon Health and Science University

Portland, Oregon, 97201, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D'Angelo S, Attia S, Riedel RF, Priebat DA, Movva S, Davis LE, Okuno SH, Reed DR, Crowley J, Butterfield LH, Salazar R, Rodriguez-Canales J, Lazar AJ, Wistuba II, Baker LH, Maki RG, Reinke D, Patel S. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol. 2017 Nov;18(11):1493-1501. doi: 10.1016/S1470-2045(17)30624-1. Epub 2017 Oct 4.

  PMID: 28988646 DERIVED

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Results Point of Contact

• Title: Research Manager
• Organization: Sarcoma Alliance for Research Through Collaboration

sarc@sarctrials.org

734-930-7600

Study Officials

• Hussein Tawbi, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: November 25, 2014
• Study Start: March 1, 2015
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: September 29, 2020
• Results First Posted: September 29, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)