Safety and Efficacy Study of SL-701, a Glioma-Associated Antigen Vaccine To Treat Recurrent Glioblastoma Multiforme

NCT02078648 | Completed Phase 1 Results DMC

• 1 other identifier: STML-701-0114
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 16

Brief Summary

The purpose of this study is to determine the safety and efficacy of SL-701 as a treatment for recurrent glioblastoma multiform (GBM).

Conditions

Adult Brain Glioblastoma; Glioblastoma Multiforme

Keywords

Glioma Associated Antigen; Vaccine; Adult; Recurrent Glioblastoma; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experiencing Regimen-limiting Toxicity (RLT)

  RLT included any events that occurred anytime through the first 12 doses of study treatment that were considered possibly, probably, or definitely related to investigational therapy and ranged from Grade ≥3 bronchospasm or Grade 2 bronchospasm that did not resolve within 24 hours despite appropriate medical treatment to cerebral edema associated with severe clinical manifestations (Grade 4) that were considered related to study therapy by the investigator.

  Approximately 24 weeks

• Number of Participants Experiencing Sudden or Unexpected Death Related to SL-701 or SL-701 in Combination With Bevacizumab

  A safety review occurred following each sudden or unexpected death that was not considered by the investigator to be a disease-related mortality and was considered to be related to SL-701.

  Day 1 through Month 12

• Overall Survival at 12 Months (OS-12)

  OS-12 was defined as the number of participants surviving at 12 months after the first injection of SL-701 and was calculated using the Clopper-Pearson Method.

  Up to 12 months

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  3 years

• Disease Control Rate (DCR)

  3 years

• Duration of Response (DoR)

  3 years

• Duration of Disease Control (DDC)

  3 years

• Progression-free Survival at 6 Months (PFS-6)

  Up to 6 months

Study Arms (2)

SL-701 + GM-CSF + Imiquimod

EXPERIMENTAL

Participants will receive SL-701 with the vaccine adjuvants granulocyte macrophage-colony stimulating factor (GM-CSF) injection and imiquimod topical cream. A complete dose of study drug consists of the administration of a sequence of 3 agents, SL-701 emulsion SC injection, GM-CSF SC injection, and imiquimod topical cream, within a 5-minute time frame. Topical application of imiquimod cream at the injection site is repeated at 24 hours after each SL-701 emulsion injection. For each participant, SL-701 emulsion (SL-701 in Montanide) will be administered by SC injection beginning on Day 1 with imiquimod topical cream 5% applied immediately (within 5 minutes of SL-701 emulsion injection) to the SL-701 emulsion injection site. In addition to the SL-701 emulsion injection, the participant will receive a SC injection of GM-CSF 150 μg close to the injection site of SL-701 emulsion. An additional dose of imiquimod cream will be applied at the same site by the participant 24 hours later.

Drug: SL-701 + GM-CSF; Drug: Imiquimod

SL-701; poly-ICLC 1.6 mg; bevacizumab

EXPERIMENTAL

SL-701 emulsion and the adjuvant poly-ICLC will be administered twice weekly for the initial 2 weeks, every 7 days during the subsequent 3 doses, and subsequently every 14 days for the subsequent 9 doses (16 doses total) through Week 22, and every 4 weeks thereafter. Bevacizumab will be administered every 2 weeks, subsequent to the administration of SL-701/poly-ICLC.

Drug: SL-701; poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethyl cellulose); Drug: Bevacizumab

Interventions

SL-701; poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethyl cellulose) DRUG

1.0 mL injection taken from 0.7 mL of SL-701 mixed at a 1:1 (v/v) ratio with 0.7 mL of Montanide. Preferred site of SC injection is in the right or left upper arms. Within 20 minutes following the administration of the SL-701 emulsion, poly-ICLC should be administered as an IM injection in the same extremity (within 3 cm whenever possible) as was administered the SL-701 (deltoid muscle, unless contraindicated).

Also known as: Avastin

SL-701; poly-ICLC 1.6 mg; bevacizumab

Bevacizumab DRUG

Following the administration of SL-701 and poly-ICLC, bevacizumab will be administered IV at a dose of 10 mg/kg. Bevacizumab infusions may occur over 30, 60 or 90 minutes in accordance with institutional practices and guidelines.

SL-701; poly-ICLC 1.6 mg; bevacizumab

SL-701 + GM-CSF DRUG

1.0 mL injection taken from 0.7 mL of SL-701 mixed at a 1:1 (v/v) ratio with 0.7 mL of Montanide. Preferred site of SC injection is in the right or left upper arms. 150 μg GM-CSF should be administered as a SC injection immediately after SL-701 emulsion administration and within 1 cm from the center of the SL-701 emulsion injection site.

SL-701 + GM-CSF + Imiquimod

Imiquimod DRUG

Within 5 minutes following the administration of the SL-701 emulsion, approximately 125 mg of imiquimod cream will be applied topically on the injection site. The imiquimod cream should be rubbed in until the cream is no longer visible.

SL-701 + GM-CSF + Imiquimod

Eligibility Criteria

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

You may qualify if:

• years of age or older.
• Histologically confirmed GBM or World Health Organization (WHO) Grade IV variants (gliosarcoma, glioblastoma with oligodendroglial features, or giant cell glioblastoma).
• Unequivocal evidence of a first tumor recurrence or progression on the initial treatment regimen (prior to enrollment on this study), consisting of surgical intervention (biopsy and/or resection), radiation, and temozolomide chemotherapy, as assessed by MRI or CT scan of the brain with or without contrast within 14 days prior to the start of SL-701. If receiving corticosteroids, the dose must be stable or decreasing for at least 5 days prior to the scan. Participants unable to undergo MRI because of non-compatible devices can be enrolled, provided CT scans are obtained and are of sufficient quality. For each participant, the same imaging technique should be performed throughout the study, for purposes of assessing tumor response or PD.
• For participants who have undergone resection of recurrent or progressive tumor prior to study enrollment, the following conditions must apply:
• Recovery from the effects of surgery.
• Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, an MRI should be performed:
• No later than 96 hours (h) in the immediate post-operative period; or
• At least 4 weeks post-craniotomy (7 days for stereotactic biopsy), within 14 days prior to the start of SL-701, and on a corticosteroid dosage that has been stable or decreasing for at least 5 days.
• Participants who have not had resection of recurrent or progressive disease must have measurable disease.
• At least 56 of the approximately 76 participants treated must have measurable disease, defined as at least one, contrast-enhancing lesion measuring at least 1 cm in 2 planes (axial, coronal, or sagittal).
• No evidence of hemorrhage on the baseline MRI or CT scan other than those that are Grade ≤ 1 and either post-operative or stable on at least two consecutive scans.
• Recovery from prior therapy toxicity, defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia and lymphopenia).
• At least 12 weeks from prior radiotherapy to the start of SL-701 unless there is new enhancement outside of the radiation field or unequivocal histopathologic evidence of recurrent tumor subsequent to radiotherapy.
• No chemotherapy or investigational agent for at least 3 weeks prior to the start of SL-701.
• Human leukocyte antigen (HLA)-A2 positive.

You may not qualify if:

• Prior cancer chemotherapy, bevacizumab (or other vascular endothelial growth factor \[VEGF\]/VEGF receptor \[VEGFR\]-directed agent), or an investigational agent for recurrent/progressive GBM or prior bevacizumab as part of initial therapy (prior chemotherapy or investigational agents are permitted as part of initial therapy; VEGF/VEGFR-directed agents are not permitted).
• Contrast-enhancing tumor that is any of the following:
• Multi-focal (defined as two separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid-attenuated inversion recovery (FLAIR) or T2 sequences);
• Associated with either diffuse subependymal or leptomeningeal dissemination; or
• ≥ 4 cm in any dimension.
• Requirement of systemic corticosteroid therapy \> 4 mg/day of dexamethasone or equivalent or requirement of increasing dose of systemic corticosteroids during the 7 days prior to the start of SL-701 treatment.
• Surgical resection or major surgical procedure within 4 weeks prior to the start of SL-701, or stereotactic biopsy within 7 days prior to the start of SL-701.
• Radiation therapy, local therapy (except for surgical re-resection), or systemic therapy following first recurrence/progressive disease. Excluded local therapies include stereotactic radiation boost, implantation of carmustine biodegradable wafers (Gliadel), intratumoral or convection-enhanced delivery administered agents, etc.
• Active infection requiring intravenous antibiotics.
• History of cancer (other than GBM) within the past 2 years that has metastatic or local recurrence potential and could negatively impact survival and/or potentially confound tumor response assessments within this study.
• Clinically significant cardiovascular disease (for example, uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction or stroke within 6 months of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus infection, Hepatitis B, or Hepatitis C, or has taken an immunosuppressive agent within 4 weeks prior to the start of SL-701 treatment. Participants with vitiligo, type 1 diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Any condition which in the investigator's opinion makes the participant unsuitable for study participation.
• Requires therapeutic anticoagulation with warfarin at baseline; participants must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed.
• Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead

Study Sites (16)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

George Washington University

Washington D.C., District of Columbia, 20052, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Piedmont Cancer Institute

Atlanta, Georgia, 30309, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Columbia University Medical Center

New York, New York, 10027, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15260, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Baylor Charles A Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

poly ICLC; Polylysine; Carboxymethylcellulose Sodium; Bevacizumab; Granulocyte-Macrophage Colony-Stimulating Factor; Imiquimod

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Lysine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Peptides; Methylcellulose; Cellulose; Glucans; Polysaccharides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Clinical Development & Medical Affairs - Solid Tumors
• Organization: Stemline Therapeutics, Inc.

clinicaltrials@menarinistemline.com

1-973-775-2845

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2014
• First Posted: March 5, 2014
• Study Start: May 1, 2014
• Primary Completion: September 1, 2017
• Study Completion: January 22, 2018
• Last Updated: February 3, 2025
• Results First Posted: December 6, 2023

Record last verified: 2025-01

Locations

US (16)