Study of Neoadjuvant Imprime PGG and Pembrolizumab for Stage III, Resectable Melanoma

NCT04995094 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: PGG-MEL2021
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

Approximately 50 ABA+ subjects with resectable, Stage III (IIIB, IIIC, or IIID) melanoma will be included in the study and randomized in a 3:2 ratio to neoadjuvant treatment with Imprime PGG plus pembrolizumab vs. pembrolizumab monotherapy. A baseline, reference biopsy and a PET/CT scan will be obtained prior to commencing 3 cycles (9 weeks) of neoadjuvant treatment with either regimen. During Week 5, subjects will provide another biopsy to assess treatment effects on the tumor and its microenvironment. At the completion of neoadjuvant treatment and before surgery, subjects will undergo another PET/CT scan to assess radiological and metabolic response compared to baseline.

Conditions

Pathologic Stage III Cutaneous Melanoma AJCC v8

Keywords

Stage III; resectable; melanoma; Imprime; Imprime PGG; pembrolizumab; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• Pathological Response Rate (pRR)

  To determine the pathological response rate (pRR) in the surgically resected specimen post completion of neoadjuvant therapy with Imprime PGG plus pembrolizumab vs pembrolizumab monotherapy

  Within 18 months of last patient enrolled

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  Within 24 months of last patient enrolled

• Incidence of Treatment-Emergent Adverse Events

  Within 24 months of last patient enrolled

• Metabolic Response Rate

  Within 24 months of last patient enrolled

• Correlation of Metabolic Response Rate (pathological response)

  Within 24 months of last patient enrolled

• Correlation of metabolic Response Rate (RECIST response)

  Within 24 months of last patient enrolled

Other Outcomes (6)

• Circulating Tumor DNA (ctDNA)

  Within 24 months of last patient enrolled

• Degree of Necrosis and Genetic Markers in Tumor Tissue

  Within 24 months of last patient enrolled

• Tumor Microenvironment (TME)

  Within 24 months of last patient enrolled

Study Arms (2)

Imprime PGG + Pembrolizumab (Investigational ARM)

EXPERIMENTAL

Imprime PGG + Pembrolizumab (Investigational ARM)

Biological: Imprime PGG; Biological: Pembrolizumab

Pembrolizumab (Control ARM)

ACTIVE COMPARATOR

Pembrolizumab (Control ARM)

Biological: Pembrolizumab

Interventions

Imprime PGG BIOLOGICAL

Imprime PGG is a soluble, β-1,3/1,6 glucan isolated from the cell wall of a proprietary Saccharomyces cerevisiae yeast strain. Imprime PGG acts as a Pathogen-Associated Molecular Pattern (PAMP). Imprime will be administered at a dose of 4 mg/kg IV over a 2-hour infusion time on Days 1, 8 and 15 of each 3-week treatment cycle.

Also known as: BTH1677

Imprime PGG + Pembrolizumab (Investigational ARM)

Pembrolizumab BIOLOGICAL

Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein. Pembrolizumab will be administered at 200 mg IV Q3W for 9 weeks.

Also known as: KEYTRUDA®

Imprime PGG + Pembrolizumab (Investigational ARM); Pembrolizumab (Control ARM)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• ≥18 years of age
• Histologically confirmed diagnosis of resectable\* AJCC (8th edition) Stage IIIB, IIIC or IIID cutaneous or unknown primary melanoma (except for any in-transit or satellite metastases) (\*Resectable Stage III disease is defined as disease that is amenable to complete tumor resection (anticipated to be an R0 resection) as judged as judged by the responsible surgeon. Criteria to judge resectability include, but are not limited to, lesions located in anatomically inaccessible areas, or invading vascular or neural structures, or technical or other reasons preventing their complete removal)
• No prior systemic treatment for melanoma (subjects who were previously resected, relapsed and are once again resectable are eligible)
• RECIST 1.1 measurable disease:
• a.) ≥ 10mm in the longest diameter for primary (if applicable) lesions or lymph node and/or ≥ 15mm in the shortest diameter for lymph nodes b) Sufficient nodal +/1 primary lesions amenable to ≥ 2 excisional/ core biopsies
• No prior radiotherapy to nodal basin
• Subject consents to provide 2 newly obtained core or excisional biopsies from non-nodal, non-bone lesions (within 28 days prior to C1D1 and during Wk 5 of treatment), the use of the resected surgical specimen and additional blood samples for translational research correlative studies
• Have peripheral blood levels of IgG anti-β-glucan antibody (ABA) of ≥ 20 mcg/mL as determined by an ELISA test prior to (within 90 days) start of study treatment
• ECOG PS 0-1 (within 7 days of starting treatment)
• Estimated life expectancy of ≥12 weeks, in the opinion of the Investigator
• Adequate organ function, including all of the following within 15 days before Day 1:
• a.) Hematological: i.) Absolute neutrophil count (ANC) ≥ 1.5×109/L (\> 1,500/mm3) (subject may not use G-CSF or GM-CSF to achieve this level) ii.) Platelets ≥ 100×109/L (\>100,000 per mm3) iii.) Hemoglobin level \>9 gm/dL. Packed red blood cell transfusion is acceptable, as long as the subject has a stable result of \>9 gm/dL for at least 1week post-transfusion. Erythropoietin should not be used to achieve this level iv.) Adequate coagulation function at screening as determined by prothrombin time (PT) International Normalized Ratio (INR) \< 1.5 times the upper limit of normal (ULN) and partial thromboplastin time (PTT) \< 1.5 times the ULN v.) Lymphocyte count \>1500 cells/mL b.) Intact immune system as demonstrated by CD4 count \>500 cells/mm3 and CD8 count \>150 cells/mm3 c.) Renal: i.) Serum creatine or measured and calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN and creatinine clearance ≥30 mL/min, per Cockcroft Gault formula d.) Hepatic: i.) Serum total bilirubin ≤1.5× ULN or direct bilirubin ≤ ULN for a subject with total bilirubin levels \>1.5× ULN ii.) AST/ALT \< 2.5 x ULN iii.) Albumin \>3 g/dL
• Have a negative PCR test at screening for SARS-COV-2 RNA
• Women of childbearing potential (WOCBP) must have 2 negative serum or urine pregnancy tests during Screening, the second within 24 hours prior to the first administration of study drug, and must agree to use highly effective physician-approved contraception from Screening to a minimum of 90 days following the last study drug administration

You may not qualify if:

• Prior therapy for melanoma (resection of a previous melanoma lesion is acceptable)
• Subjects with uveal or mucosal melanoma
• Pregnant, lactating or not practicing adequate contraception (premenopausal women), or expecting to conceive or father children within the duration of the trial, starting from Screening to 90 days following the last dose of drug administration
• Prior radiotherapy in the previous 2 weeks. Radiotherapy to presenting tumor is prohibited
• Administration of a live, attenuated vaccine within 28 days prior to Day 1 or anticipation that such a live attenuated vaccine will be required during the study
• History of autoimmune disease, including but not limited to inflammatory bowel disease, systemic lupus erythematosus, and autoimmune hepatitis, requiring systemic treatment in previous 12 months
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone \[\>10mg\], dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 15 days prior to Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
• Immunodeficiency, natural or iatrogenic (steroids, immunosuppressants)
• History of malignancy within the last 3 years. Subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years
• Known CNS metastasis of leptomeningeal disease
• Known history of HIV, Hepatitis B, active Hepatitis C or tuberculosis
• History of pneumonitis including interstitial lung disease
• Has a known hypersensitivity to any component of protocol therapy, or their vehicle(s)
• Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NYHA Grade 2), unstable angina pectoris, cardiac arrhythmia, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or psychiatric illness
• Has a fever \>38oC within 3 days before the first dose of study treatment

Sponsors & Collaborators

• HiberCell, Inc.: lead

Study Sites (4)

UC San Diego Moores Cancer Center

La Jolla, California, 92093-0990, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Ichan School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

BTH1677; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: August 6, 2021
• Study Start: August 15, 2021
• Primary Completion: February 18, 2023
• Study Completion: May 18, 2023
• Last Updated: November 5, 2021

Record last verified: 2021-10

Locations

US (4)