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Trial record 3 of 13 for:    Biothera

Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT02981303
Recruitment Status : Recruiting
First Posted : December 5, 2016
Last Update Posted : May 11, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Biothera

Brief Summary:

Objective: To determine the Overall Response Rate (ORR) to Imprime PGG + pembrolizumab in subjects with advanced melanoma or metastatic TNBC

Safety: To characterize the safety of Imprime PGG + pembrolizumab given in combination

Hypothesis: Restore (for melanoma) or enhance (for TNBC) sensitivity to checkpoint inhibitors (CPI) by appropriate and effective stimulation of the subject's innate and adaptive immune systems in those subjects who have failed 1st line therapy

The study will incorporate Simon's optimal 2-stage design with sample size fixed at 12 subjects each in Stage 1 for advanced melanoma and for Triple Negative Breast Cancer (TNBC) subjects. The safety criterion of ≤ 4 (or ≤ 33%) subjects with Grade 3/4 adverse events in Cycle 1 within either tumor type must be met in order to proceed to Stage 2. The starting dose is 4 mg/kg for Imprime PGG. In the event there are a total of > 4 (or > 33%) of subjects with Grade 3/4 adverse events in Cycle 1, the dose of Imprime PGG will be reduced to 2 mg/kg, and Stage 1 will be repeated at a dose of 2 mg/kg with an additional cohort of n=12 subjects. For the dose that meets the safety criterion in Stage 1, at least 1 response in melanoma subjects and 2 responses in TNBC subjects amongst the 12 subjects within each tumor type must be observed in order to proceed to Stage 2.

Stage 2 will enroll an additional 17 subjects with melanoma, and 30 subjects with TNBC. For the dose that meets the Stage 1 safety criterion, success will be declared if at least 4 amongst the total of up to 29 subjects with melanoma, and 13 amongst the total of up to 42 subjects with TNBC achieve an objective response.


Condition or disease Intervention/treatment Phase
Advanced Melanoma Triple-Negative Breast Cancer Biological: Imprime PGG Drug: Pembrolizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Phase 2 Study of Imprime PGG and Pembrolizumab in Subjects With Advanced Melanoma Failing Front-line Treatment With Checkpoint Inhibitors (CPI) or Triple Negative Breast Cancer (TNBC) Failing Front-line Chemotherapy for Metastatic Disease
Study Start Date : December 2016
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Melanoma
Imprime PGG + Pembrolizumab
Biological: Imprime PGG
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.
Other Name: Imprime
Drug: Pembrolizumab
Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 protein. Pembrolizumab will be given at a fixed dose of 200 mg IV over 30 minutes on Day 1 of each 3-week treatment cycle after the Imprime infusion.
Other Name: Keytruda
Experimental: Triple Negative Breast Cancer
Imprime PGG + Pembrolizumab
Biological: Imprime PGG
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.
Other Name: Imprime
Drug: Pembrolizumab
Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 protein. Pembrolizumab will be given at a fixed dose of 200 mg IV over 30 minutes on Day 1 of each 3-week treatment cycle after the Imprime infusion.
Other Name: Keytruda



Primary Outcome Measures :
  1. Overall Response Rate (ORR) to Imprime PGG + pembrolizumab using RECIST v1.1 criteria [ Time Frame: Within 18 months of last patient enrolled ]

Secondary Outcome Measures :
  1. Time to response (TTR) using RECIST v1.1 criteria [ Time Frame: Within 24 months of last patient enrolled ]
  2. Complete response rate (CRR) using RECIST v1.1 criteria [ Time Frame: Within 24 months of last patient enrolled ]
  3. Duration of overall response (DoR) using RECIST v1.1 criteria [ Time Frame: Within 24 months of last patient enrolled ]
  4. Progression-Free Survival (PFS) and PFS rate at 6 months and 1 year using RECIST v1.1 criteria [ Time Frame: Within 24 months of last patient enrolled ]
  5. Overall survival (OS) and OS rate at 1 year using RECIST v1.1 criteria [ Time Frame: Within 24 months of last patient enrolled ]
  6. Pharmacokinetic (PK) data of Imprime PGG in combination with Pembrolizumab [ Time Frame: Within 24 months of last patient enrolled ]
    Correlate serum Imprime PGG concentration/time relationship


Other Outcome Measures:
  1. ORR based on irRECIST [ Time Frame: Within 24 months of last patient enrolled ]
  2. PFS based on irRECIST [ Time Frame: Within 24 months of last patient enrolled ]
  3. Correlate levels of baseline serum anti-β-glucan antibody (ABA) with objective response and treatment outcomes [ Time Frame: Within 24 months of last patient enrolled ]
  4. Correlate changes in immune cell activation markers, such as CD86 expression in tumor biopsy samples* and in peripheral blood immune cells with objective response and treatment outcome [ Time Frame: Within 24 months of last patient enrolled ]
  5. In tumor biopsies, correlate changes in the tumor immune microenvironment including TILs (Tumor-infiltrating Lymphocytes) and tumor-infiltrating myeloid cells with objective response and treatment outcome [ Time Frame: Within 24 months of last patient enrolled ]
  6. Correlate PD-L1 expression in tumor biopsy samples (in tumor cells and myeloid cells) with objective response and treatment outcome [ Time Frame: Within 24 months of last patient enrolled ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have signed an informed document prior to any study-specific procedures or treatment
  2. Be ≥ 18 years of age at time of consent
  3. For Melanoma Subjects: Have histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic (Stage IV) melanoma not amenable to local therapy, and irrespective of PD-L1 status
  4. For TNBC Subjects: Have histologically or cytologically confirmed diagnosis of metastatic (Stage IV) TNBC, and irrespective of PD-L1 status. TNBC is defined as negative immunohistochemistry (IHC) assays for Estrogen Receptor (ER), and Progesterone Receptor (PR), and HER2 negative (IHC 0 or 1+, or 2+ by IHC confirmed negative by FISH)
  5. Have documented objective radiographic or clinical disease progression after PD-1/PD-L1 +/- anti-CTLA-4 inhibitor therapy (melanoma) or after at least 1 line of chemotherapy for metastatic disease (TNBC)
  6. Have resolution of all previous treatment-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (less than or equal to Grade 2) or alopecia. If subject received major surgery or radiation therapy of > 30 Gy, must have recovered from the toxicity and/or complications from the intervention.
  7. Have at least one radiologically measurable lesion as per RECIST v1.1 defined as a lesion that is at least 10 mm in longest diameter or lymph node that is at least 15 mm in short axis imaged by CT scan or MRI and obtained by imaging within 28 days prior to start of study treatment. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  8. Have peripheral blood levels of IgG anti-β-glucan antibody (ABA) of ≥ 20 mcg/mL as determined by an ELISA test within 28 days prior to start of study treatment
  9. Be willing to consider providing fresh tissue for biomarker analysis, and, based on the adequacy of the tissue sample quality, for assessment of biomarker status. Repeat samples may be required if adequate tissue is not provided. Newly obtained biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded block specimens are preferred to slides.

    Note: Information on 1 tumor biopsy sample is mandatory and is as follows: (1) To determine eligibility, historical (diagnostic) tumor biopsy official pathology report +/- an archival sample. Additional biopsy samples, preferably obtained from the same localized region, are highly desirable when feasible at the following time points: (2) Sample before the first dose of study treatment, (3) Sample after completion of Cycle 2 but before the start of Cycle 3 dosing, and (4) Sample either at the time of response or at the End of Study Visit (if no response).

  10. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 14.3)
  11. Have life expectancy of 3 months or greater as determined by the treating physician
  12. Have adequate organ function (all screening labs should be performed within 15 days prior to treatment initiation):

    1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN
    2. Aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
    3. Alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
  13. Have adequate renal function as defined by the following criteria:

    Creatinine ≤ 1.5 x ULN and CrCl ≥ 30 ml/min per Cockcroft Gault formula:

  14. Have adequate hematologic function, defined as meeting all of the following criteria:

    1. Hemoglobin ≥ 9 g/dL (uncorrected by RBC transfusion)
    2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
    3. Platelet count ≥ 100 × 109/L
  15. Have adequate coagulation functioning within 15 days prior to start of study treatment, defined by either of the following criteria:

    1. INR < 1.5 × ULN
    2. OR for subjects receiving warfarin or low molecular weight heparin (LMWH), the subjects must, in the Investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
    3. Activated Partial Thromboplastin Time (aPTT) < 1.5 × ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  16. Female subjects of childbearing potential as defined in Section 5.7.2 must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  17. If of childbearing potential as defined in Section 5.7.2, must be willing to use an adequate method of contraception (see Section 5.7.2) from the first dose of study medication through 120 days after the last dose of study medication
  18. Be willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

  1. Has disease that is suitable for local therapy administered with curative intent
  2. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  3. Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
  4. Has known history of active tuberculosis
  5. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  6. Has known active Hepatitis B (eg, HBsAg reactive) or Hepatitis C (eg, HCV RNA [qualitative] is detected
  7. Has a history of clinically severe autoimmune disease, or history of organ transplant
  8. Has a history of ocular melanoma
  9. Has known hypersensitivity to baker's yeast
  10. Had previous exposure to Betafectin® or Imprime PGG
  11. Has hypersensitivity to pembrolizumab or any of its excipients
  12. Had a prior anti-cancer monoclonal antibody (except immune CPI in the case of melanoma subjects) within 30 days prior to start of study treatment, or failure to recover to CTCAE Grade 1 or better from the adverse events of prior therapies
  13. Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Study Day 1 or who has not recovered from adverse events due to a previously administered agent or major surgery
  14. Has 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
  15. Has known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  16. Has known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  17. Has active autoimmune disease requiring systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteriod replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  18. Has evidence of (non-infectious) pneumonitis that required steroids or current pneumonitis
  19. Has a history of interstitial lung disease
  20. Has an active infection requiring systemic therapy
  21. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator
  22. Has a clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome within ≤180 days prior to start of study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  23. Has a known psychiatric or substance abuse disorder(s) that would interfere with informed consent or cooperation with the requirements of the trial
  24. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  25. With TNBC has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4, or anti-PD-L2 agent
  26. Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02981303


Contacts

Locations
United States, Arizona
Arizona Center for Cancer Care Recruiting
Avondale, Arizona, United States, 85392
Contact: Victoria Noboa    623-536-2580    VNOBOA@ARIZONACCC.COM   
Principal Investigator: Clarence Adoo, M.D., FACP         
United States, California
John Wayne Cancer Institute Recruiting
Santa Monica, California, United States, 90404
Contact: Linda Lepe    310-582-7249    Linda.Lepe2@providence.org   
Principal Investigator: Steven O'Day, M.D.         
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Paula Fisk    720-848-0676    Paula.Fisk@ucdenver.edu   
Contact: Brad McKay       Brad.McKay@ucdenver.edu   
Principal Investigator: Virginia Borges, MD         
Sarah Cannon Research Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Lori Hannan    720-754-4649    Lori.Hannan@scresearch.net   
Contact: Holly Gindes    720-754-4630    Holly.Gindes@helathonecares.com   
Principal Investigator: Gerald Falchook, MD         
United States, Georgia
University Cancer and Blood Center Recruiting
Athens, Georgia, United States, 30607
Contact: Jamie Hodgson    706-353-2990 ext 279    jhodgson@universitycancer.com   
Principal Investigator: Petros Nikolinakos, MD         
Piedmont Cancer Institute Recruiting
Atlanta, Georgia, United States, 30318
Contact: Polly Searcy    678-298-3238    psearcy@piedmontcancerinstitute.com   
Principal Investigator: Rajni Sinha, MD         
United States, New York
Stony Brook University Cancer Center Recruiting
Stony Brook, New York, United States, 11794
Contact: Jennifer Hofecker    631-638-0857    Jennifer.Hofecker@stonybrookmedicine.edu   
Contact: Patricia Delli Bovi       Patricia.DelliBovi@stonybrookmedicine.edu   
Principal Investigator: Alison Stopeck, MD         
United States, Pennsylvania
Thomas Jefferson University Sidney Kimmel Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Noelle Sowers    215-955-0087    Noelle.Sowers@jefferson.edu   
Contact: Rita Murphy    215-955-9626    Rita.Murphy@jefferson.edu   
Principal Investigator: Maysa Abu-Khalaf, MD         
United States, Texas
Millennium Oncology Recruiting
Houston, Texas, United States, 77090
Contact: John Waldron    877-870-2640    JWaldron@wmrad.com   
Principal Investigator: Mary Crow, MD         
Sponsors and Collaborators
Biothera
Merck Sharp & Dohme Corp.

Responsible Party: Biothera
ClinicalTrials.gov Identifier: NCT02981303     History of Changes
Other Study ID Numbers: BT-CL-PGG-MEL/BCA-1621/MK3475
First Posted: December 5, 2016    Key Record Dates
Last Update Posted: May 11, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Breast Neoplasms
Melanoma
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Antineoplastic Agents