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Pathologic Stage III Cutaneous Melanoma AJCC v8Phase 2NCT04995094

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

A Phase 2 study testing Imprime PGG and Pembrolizumab in people with Pathologic Stage III Cutaneous Melanoma AJCC v8, run by HiberCell, Inc. at 4 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Imprime PGG and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
4 sitesUnited States
Study dates
15 Aug 2021to 18 May 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Willing and able to comply with all protocol-specified assessments and the study visit schedule.

Who cannot join

  • 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
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  • 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
  • Had previous exposure to Imprime PGG
  • Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF, or recombinant erythropoietin) within 4 weeks prior to Study Day 1
  • Any condition which could interfere with, or the treatment for which might interfere with the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the subject's risk by participating in the study
  • Subject is under legal custodianship
  • First-degree relatives of the investigator, study staff or the sponsor.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093-0990

  • Ichan School of Medicine at Mount Sinai

    New York, New York, 10029

  • Allegheny Health Network

    Pittsburgh, Pennsylvania, 15212

  • Innovative Clinical Research Institute

    Whittier, California, 90603

Other trials in United States

About this study

Official title: A Phase II, Neoadjuvant, Randomized, Multicenter Study of Imprime PGG Plus Pembrolizumab in Subjects With Stage III, Resectable Melanoma

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.

Read the detailed description

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.

Subjects will then undergo surgical resection. A pre-surgical assessment of operability will be done by the responsible surgeon, and the investigator will ensure that adverse events occurring during the treatment period have resolved to the minimal acceptable level that would not place the subject at undue risk or delay surgery for more than 1 week after the last dose of Imprime or 3 weeks after last dose of pembrolizumab, when subjects will undergo surgical resection.

The surgical specimen will be locally and centrally assessed by a pathologist to determine the pathological response (pCR, pMR, pPR) induced by the neoadjuvant treatment (central read will be blinded). Following surgery, subjects will be followed for safety for 90 days. The total duration of systemic treatment will be 3 cycles (9 weeks). In the Investigational arm, surgery should be performed no more than a week after the subject's last dose of Imprime PGG and in the Control arm, surgery should be performed within 3 weeks of the subject's last dose of pembrolizumab.

Being tested
Imprime PGG, Pembrolizumab
Keywords
Stage III, resectable, melanoma, Imprime, Imprime PGG, pembrolizumab, neoadjuvant
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Imprime PGGBiological

    Also called BTH1677

    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.

  • PembrolizumabBiological

    Also called KEYTRUDA®

    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.

Study groups in NCT04995094
Study groupRoleWhat they receive
Imprime PGG + Pembrolizumab (Investigational ARM)ExperimentalImprime PGG + Pembrolizumab (Investigational ARM)
Receives: Biological: Imprime PGG; Biological: Pembrolizumab
Pembrolizumab (Control ARM)Active comparatorPembrolizumab (Control ARM)
Receives: Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Within 18 months of last patient enrolled

Secondary outcomes (9)

  1. Overall Response Rate (ORR)

    Radiological overall response rate (ORR) (by RECIST 1.1)

    Measured: Within 24 months of last patient enrolled

  2. Incidence of Treatment-Emergent Adverse Events

    Safety of neoadjuvant treatment (incidence of treatment-emergent adverse events, change from baseline in physical findings, ECGs, and laboratory results)

    Measured: Within 24 months of last patient enrolled

  3. Metabolic Response Rate

    Metabolic Response Rate (assessed by PET per EORTC recommendations)

    Measured: Within 24 months of last patient enrolled

  4. Correlation of Metabolic Response Rate (pathological response)

    Correlation of metabolic response rate with pathological response

    Measured: Within 24 months of last patient enrolled

  5. Correlation of metabolic Response Rate (RECIST response)

    Correlation of metabolic response rate with RECIST response.

    Measured: Within 24 months of last patient enrolled

  6. Correlation of Pathological Response Rate (RECIST)

    Correlation of pathological response rate with RECIST response

    Measured: Within 24 months of last patient enrolled

  7. Incidence of Surgical Delays or Complications

    Incidence of surgical delays or complications, including post-operative infections

    Measured: Within 24 months of last patient enrolled

  8. Opinion of Operability

    Comparison pre and post treatment portion of participants with disease amendable to complete tumor resection as judged by the responsible surgeon to compare surgeon's opinion of operability

    Measured: Within 24 months of last patient enrolled

  9. Severity of treatment-emergent adverse events

    Safety of neoadjuvant treatment (treatment-emergent adverse events, change from baseline in physical findings, ECGs, and laboratory results)

    Measured: Within 24 months of last patient enrolled

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2021
  2. Study start15 Aug 2021
  3. Primary completion18 Feb 2023 (estimated)
  4. Study completion18 May 2023 (estimated)

Why it stopped: Enrollment challenges, study not feasible

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04995094
Sponsor's protocol ID
PGG-MEL2021
Status last verified
Oct 2021
First submitted
19 Jul 2021
Last updated
5 Nov 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Imprime PGG and Pembrolizumab in people with Pathologic Stage III Cutaneous Melanoma AJCC v8, run by HiberCell, Inc. at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Response Rate (pRR) (time frame: Within 18 months of last patient enrolled). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04995094.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.

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