Advanced MelanomaPhase 2NCT02981303
Study of Imprime PGG and Pembrolizumab in Advanced Melanoma and Triple Negative Breast Cancer
A Phase 2 study testing Imprime PGG and Pembrolizumab in people with Advanced Melanoma and Triple-Negative Breast Cancer, run by HiberCell, Inc. at 10 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Melanoma, Triple-Negative Breast Cancer
- 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
- 64 participants
- Where
- 10 sitesUnited States
- Study dates
- 22 Feb 2017to 31 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Have signed an informed document prior to any study-specific procedures or treatment
- Be ≥ 18 years of age at time of consent
- 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
- 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)
- 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)
- 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.
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- 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.
- 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
- 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).
- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 14.3)
- Have life expectancy of 3 months or greater as determined by the treating physician
- Have adequate organ function (all screening labs should be performed within 15 days prior to treatment initiation):
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
- Alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
- Have adequate renal function as defined by the following criteria:
- Creatinine ≤ 1.5 x ULN and CrCl ≥ 30 ml/min per Cockcroft Gault formula:
- Have adequate hematologic function, defined as meeting all of the following criteria:
- Hemoglobin ≥ 9 g/dL (uncorrected by RBC transfusion)
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- Platelet count ≥ 100 × 109/L
- Have adequate coagulation functioning within 15 days prior to start of study treatment, defined by either of the following criteria:
- INR < 1.5 × ULN
- 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.
- 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
- 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.
- 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
- Be willing and have the ability to comply with scheduled visits (including geographical proximity), treatment plans, laboratory tests, and other study procedures
Who cannot join
- Has disease that is suitable for local therapy administered with curative intent
- 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
- 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.
- Has known history of active tuberculosis
- Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Has known active Hepatitis B (eg, HBsAg reactive) or Hepatitis C (eg, HCV RNA [qualitative] is detected
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- Has a history of clinically severe autoimmune disease, or history of organ transplant
- Has a history of ocular melanoma
- Has known hypersensitivity to baker's yeast
- Had previous exposure to Betafectin® or Imprime PGG
- Has hypersensitivity to pembrolizumab or any of its excipients
- 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
- 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
- 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
- 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.
- 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.
- 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 corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Has evidence of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has a history of interstitial lung disease
- Has an active infection requiring systemic therapy
- 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
- 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
- Has a known psychiatric or substance abuse disorder(s) that would interfere with informed consent or cooperation with the requirements of the trial
- 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
- With TNBC has received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4, or anti-PD-L2 agent
- Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University Cancer and Blood Center
Athens, Georgia, 30607
Piedmont Cancer Institute
Atlanta, Georgia, 30318
University of Colorado Cancer Center
Aurora, Colorado, 80045
Arizona Center for Cancer Care
Avondale, Arizona, 85392
Sarah Cannon Research Institute
Denver, Colorado, 80218
Millennium Oncology
Houston, Texas, 77090
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Thomas Jefferson University Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
John Wayne Cancer Institute
Santa Monica, California, 90404
Stony Brook University Cancer Center
Stony Brook, New York, 11794
About this study
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 TNBC Failing Front-line Chemotherapy for Metastatic Disease
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
Read more
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.
- Conditions
- Advanced Melanoma, Triple-Negative Breast Cancer
- Being tested
- Imprime PGG, Pembrolizumab
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imprime PGGBiological
Also called Imprime
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.
PembrolizumabDrug
Also called Keytruda
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.
| Study group | Role | What they receive |
|---|---|---|
| Melanoma | Experimental | Imprime PGG + Pembrolizumab Receives: Biological: Imprime PGG; Drug: Pembrolizumab |
| Triple Negative Breast Cancer | Experimental | Imprime PGG + Pembrolizumab Receives: Biological: Imprime PGG; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Efficacy Endpoint Was ORR, Defined as the Proportion of Subjects Demonstrating CR or PR Based on RECIST v1.1 Criteria.
The best response was defined as the best response recorded from the start of study treatment until the first PD based on RECIST v1.1 or start of new cancer therapy, whichever occurred earlier.
Response assessment occurred every 6 weeks after the first dose of study drug.
Measured: From the start of study treatment until the first PD based on RECIST v1.1 or start of new cancer therapy, whichever occurred earlier, up to 24 months.
Secondary outcomes (5)
Time to Response (TTR) Using RECIST v1.1 Criteria
For the subset of subjects with a confirmed CR or PR (RECIST v1.1), TTR was defined as time from the date of the first dose to the first response (the CR/PR prior to the confirmation).
Measured: TTR was defined as time from the date of the first dose to the first response, up to 24 months.
Complete Response Rate (CRR)
Complete response rate (CRR) using RECIST v1.1 criteria
Measured: The time from the date of the first dose to the first response (CR), up to 24 months.
Duration of Overall Response (DoR) Using RECIST v1.1 Criteria
For the subset of subjects with a confirmed CR or PR (RECIST v1.1), DoR was defined as the time from the first documented evidence of CR or PR (the response prior to the confirmation) until the time of documented PD (based on radiological assessments per RECIST v1.1) or death due to any cause, whichever occurred earlier.
Measured: time from the first documented evidence of CR or PR (the response prior to the confirmation) until the time of documented PD (based on radiological assessments per RECIST v1.1) or death due to any cause, whichever occurred earlier.
Progression-Free Survival (PFS) Per RECISTv1.1
Progression free survival was defined as the time from the date of the first dose until the first PD or death due to any cause, whichever occurred first.
Measured: time from the date of the first dose until the first PD or death due to any cause, whichever occurred first.
Overall Survival (OS)
Overall survival was defined as the time from the date of the first dose until the date of death due to any causes.
Measured: Time from date of study day 1 until date of death due to any cause.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study start22 Feb 2017
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Advanced MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- HiberCell, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Jeremy D Graff, PhD, Study director, HiberCell, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981303
- Sponsor's protocol ID
- BT-CL-PGG-MEL/BCA-1621/MK3475
- Status last verified
- Jun 2024
- First submitted
- 22 Nov 2016
- Last updated
- 9 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alison Stopeck, Michele Anne Gargano, Nick Niles, Blaine Rathmann, Michael Jon Chisamore, Nandita Bose, and Jose Luis Iglesias. A multicenter, open-label, phase 2 study of odetiglucan (IMPRIME PGG) and pembrolizumab in patients with metastatic breast cancer (mBCA) who have progressed through prior hormonal therapy. Journal of Clinical Oncology. 2022; Volume 40, Number 16_suppl. https://doi.org/10.1200/JCO.2022.40.16_suppl.TPS1115
Chan ASH, Kangas TO, Qiu X, Uhlik MT, Fulton RB, Ottoson NR, Gorden KB, Yokoyama Y, Danielson ME, Jevne TM, Michel KS, Graff JR, Bose N. Imprime PGG Enhances Anti-Tumor Effects of Tumor-Targeting, Anti-Angiogenic, and Immune Checkpoint Inhibitor Antibodies. Front Oncol. 2022 May 26;12:869078. doi: 10.3389/fonc.2022.869078. eCollection 2022.
PubMed 35692755Steven O'Day, Virginia F. Borges, Bartosz Chmielowski, Ruta D. Rao, Maysa M. Abu-Khalaf, Alison Stopeck, Petros Nikolinakos, Melinda L. Telli, Bin Xie, Montaser F. Shaheen, Paulette Mattson, Michele Anne Gargano, Joanna Cox, Vassiliki Karantza, Michael Jon Chisamore, Bruno Osterwalder, Nandita Bose, Mark T. Uhlik, and Jeremy Graff. An open label, multicenter phase II study combining imprime PGG (PGG) with pembrolizumab (P) in previously treated metastatic triple-negative breast cancer (mTNBC). Journal of Clinical Oncology. 2019; Volume 37, Number 15_suppl. https://doi.org/10.1200/JCO.2019.37.15_suppl.2550
Uhlik M, et al. Response and clinical benefit assessment of the combination of the Dectin-1 agonist Imprime PGG and anti-PD-1 Pembrolizumab in chemotherapy-resistant metastatic triple negative breast cancer. San Antonio Breast Cancer Symposium. 2019. PD-02.
Breast Cancer Plenary Session: O'Day S, et al. A phase 2 trial of pembrolizumab and a novel innate immune activator, Imprime PGG, in metastatic triple negative breast cancer. AACR 2020. (#10531)
Late Breaking Abstract: Chan ASH, et al. Clinical benefit evident with early immunopharmacodynamic responses in prior-checkpoint failed metastatic melanoma patients treated with Imprime PGG and Pembrolizumab. SITC 2019. (#P862)
Stopeck AT, Abu-Khalaf M, Borges V, Chmielowski B, Rao R, Xie B, Dudek AZ, Mina L, O'Shaughnessy J, Chisamore M, Mattson P, Gargano M, Cox J, Osterwalder B, Drees J, Harrison B, Chan ASH, Qiu X, Ottoson N, Bose N, Uhlik M, Graff J, Iglesias J. Phase 2 trial of imprime and pembrolizumab immunotherapy in metastatic triple negative breast cancer patients who have progressed beyond first line chemotherapy. J Immunol. 2025 Jul 1;214(7):1529-1538. doi: 10.1093/jimmun/vkaf079.
PubMed 40338159
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 TNBC Failing Front-line Chemotherapy for Metastatic Disease
- ClinicalTrials.gov ID
- NCT02981303
- Acronym / sponsor ID
- BT-CL-PGG-MEL/BCA-1621/MK3475
- Conditions
- Advanced Melanoma, Triple-Negative Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- HiberCell, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 22 Feb 2017 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 5 Dec 2016 (estimated)
- Results
- Posted 9 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melanoma | Experimental | Biological: Imprime PGG, Drug: PembrolizumabImprime PGG + Pembrolizumab |
| Triple Negative Breast Cancer | Experimental | Biological: Imprime PGG, Drug: PembrolizumabImprime PGG + Pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Have signed an informed document prior to any study-specific procedures or treatment
- Be ≥ 18 years of age at time of consent
- 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
- 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)
- 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)
Key exclusion criteria (26 listed)
- Has disease that is suitable for local therapy administered with curative intent
- 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
- 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.
- Has known history of active tuberculosis
- Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imprime PGGAlso: ImprimeImprime 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. | Biological | Melanoma, Triple Negative Breast Cancer |
| PembrolizumabAlso: KeytrudaPembrolizumab 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. | Drug | Melanoma, Triple Negative Breast Cancer |
Primary outcome
The Primary Efficacy Endpoint Was ORR, Defined as the Proportion of Subjects Demonstrating CR or PR Based on RECIST v1.1 Criteria.
Time frame: From the start of study treatment until the first PD based on RECIST v1.1 or start of new cancer therapy, whichever occurred earlier, up to 24 months.
The best response was defined as the best response recorded from the start of study treatment until the first PD based on RECIST v1.1 or start of new cancer therapy, whichever occurred earlier. Response assessment occurred every 6 weeks after the first dose of study drug.
5 secondary outcomes
Time to Response (TTR) Using RECIST v1.1 Criteria
Time frame: TTR was defined as time from the date of the first dose to the first response, up to 24 months.
Complete Response Rate (CRR)
Time frame: The time from the date of the first dose to the first response (CR), up to 24 months.
Duration of Overall Response (DoR) Using RECIST v1.1 Criteria
Time frame: time from the first documented evidence of CR or PR (the response prior to the confirmation) until the time of documented PD (based on radiological assessments per RECIST v1.1) or death due to any cause, whichever occurred earlier.
Progression-Free Survival (PFS) Per RECISTv1.1
Time frame: time from the date of the first dose until the first PD or death due to any cause, whichever occurred first.
Overall Survival (OS)
Time frame: Time from date of study day 1 until date of death due to any cause.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundAlison Stopeck, Michele Anne Gargano, Nick Niles, Blaine Rathmann, Michael Jon Chisamore, Nandita Bose, and Jose Luis Iglesias. A multicenter, open-label, phase 2 study of odetiglucan (IMPRIME PGG) and pembrolizumab in patients with metastatic breast cancer (mBCA) who have progressed through prior hormonal therapy. Journal of Clinical Oncology. 2022; Volume 40, Number 16_suppl. https://doi.org/10.1200/JCO.2022.40.16_suppl.TPS1115
- Background: PubMed 35692755Chan ASH, Kangas TO, Qiu X, Uhlik MT, Fulton RB, Ottoson NR, Gorden KB, Yokoyama Y, Danielson ME, Jevne TM, Michel KS, Graff JR, Bose N. Imprime PGG Enhances Anti-Tumor Effects of Tumor-Targeting, Anti-Angiogenic, and Immune Checkpoint Inhibitor Antibodies. Front Oncol. 2022 May 26;12:869078. doi: 10.3389/fonc.2022.869078. eCollection 2022.
- Results publicationSteven O'Day, Virginia F. Borges, Bartosz Chmielowski, Ruta D. Rao, Maysa M. Abu-Khalaf, Alison Stopeck, Petros Nikolinakos, Melinda L. Telli, Bin Xie, Montaser F. Shaheen, Paulette Mattson, Michele Anne Gargano, Joanna Cox, Vassiliki Karantza, Michael Jon Chisamore, Bruno Osterwalder, Nandita Bose, Mark T. Uhlik, and Jeremy Graff. An open label, multicenter phase II study combining imprime PGG (PGG) with pembrolizumab (P) in previously treated metastatic triple-negative breast cancer (mTNBC). Journal of Clinical Oncology. 2019; Volume 37, Number 15_suppl. https://doi.org/10.1200/JCO.2019.37.15_suppl.2550
- Results publicationUhlik M, et al. Response and clinical benefit assessment of the combination of the Dectin-1 agonist Imprime PGG and anti-PD-1 Pembrolizumab in chemotherapy-resistant metastatic triple negative breast cancer. San Antonio Breast Cancer Symposium. 2019. PD-02.
- Results publicationBreast Cancer Plenary Session: O'Day S, et al. A phase 2 trial of pembrolizumab and a novel innate immune activator, Imprime PGG, in metastatic triple negative breast cancer. AACR 2020. (#10531)
- Results publicationLate Breaking Abstract: Chan ASH, et al. Clinical benefit evident with early immunopharmacodynamic responses in prior-checkpoint failed metastatic melanoma patients treated with Imprime PGG and Pembrolizumab. SITC 2019. (#P862)
- Derived from this study: PubMed 40338159Stopeck AT, Abu-Khalaf M, Borges V, Chmielowski B, Rao R, Xie B, Dudek AZ, Mina L, O'Shaughnessy J, Chisamore M, Mattson P, Gargano M, Cox J, Osterwalder B, Drees J, Harrison B, Chan ASH, Qiu X, Ottoson N, Bose N, Uhlik M, Graff J, Iglesias J. Phase 2 trial of imprime and pembrolizumab immunotherapy in metastatic triple negative breast cancer patients who have progressed beyond first line chemotherapy. J Immunol. 2025 Jul 1;214(7):1529-1538. doi: 10.1093/jimmun/vkaf079.
- Individual participant dataSharing planned: No
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Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy D Graff, PhD study director
HiberCell, Inc.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imprime PGG and Pembrolizumab in people with Advanced Melanoma and Triple-Negative Breast Cancer, run by HiberCell, Inc. at 10 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 29 inclusion and 26 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: finished, as of the sponsor's last update on 9 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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?
Yes. Results are posted in the registry (first posted 9 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Primary Efficacy Endpoint Was ORR, Defined as the Proportion of Subjects Demonstrating CR or PR Based on RECIST v1.1 Criteria. (time frame: From the start of study treatment until the first PD based on RECIST v1.1 or start of new cancer therapy, whichever occurred earlier, up to 24 months.). 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 NCT02981303, which also lists 7 linked publications.
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 9 Jul 2024.