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Study of Intratumoral G100 With Or Without Pembrolizumab or Rituximab In Participants With Follicular Non-Hodgkin's Lymphoma (MK-3475-174/IMDZ-G142)

Sponsor
Immune Design (Industry)
Overall Status
Terminated
CT.gov ID
NCT02501473
Collaborator
Merck Sharp & Dohme LLC (Industry)
52
Enrollment
8
Arms
41.9
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase 1/2 open label trial of G100 in participants with low grade Non-Hodgkin's Lymphoma (NHL). G100 is composed of glucopranosyl lipid A in a stable emulsion and is a potent TLR4 (toll-like receptor-4) agonist. G100 will be administered by direct injection (intratumorally) into tumors of low grade NHL with or without standard low dose radiation therapy. Preclinical models and clinical studies in other cancers such as Merkel cell carcinoma have demonstrated that G100 administered in this manner can alter the tumor microenvironment, activate dendritic cells, T cells and other immune cells and induce systemic anti-tumor immune responses. In this trial, the safety, immunogenicity, and preliminary clinical efficacy of G100 will be examined alone or with pembrolizumab.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

This is a multi-center Phase 1/2 open label trial of intratumoral G100 in participants with low grade NHL. Eligible participants with NHL will be enrolled and receive G100 to an accessible tumor mass. Clinical response will be evaluated in the injected tumor and systemic (abscopal) responses will be evaluated in distal areas involved with tumor.

The study will be conducted in 5 parts. In Part 1, Dose Escalation, 2 sequentially enrolled cohorts of participants will be treated at one of 2 dose levels of G100 using a standard escalation design. In this portion of the study, both follicular and marginal zone NHL will be eligible. In Part 2, 2 groups of participants with follicular NHL may be examined. One group will be randomly assigned to receive either single agent G100 intratumorally at the maximum safe dose determined in Part 1 following local radiation or will receive the same treatment regimen sequentially administered with pembrolizumab. A second treatment group may be explored if the safety profile in Part 1 is acceptable. In this optional group, participants with injectable tumors of 4 cm or greater would be enrolled and treated with a higher dose of G100. In Part 3, expansion of a higher dose (20µg of G100) in participants with follicular NHL will be enrolled to receive local radiation therapy and intratumoral G100. In Part 4, Dose Escalation and Expansion, a dose of 20µg of G100 will be examined as a treatment of 1 or more tumors (up to 4) with pembrolizumab in order to establish safety and examine clinical and biomarker responses in participants receiving increasing total systemic doses of G100 and Part 5, will evaluate standard induction therapy with rituximab (anti-CD20) in combination of escalating doses of intratumoral G100 in single tumors.

The primary goal of this study is to determine the safety and tolerability of different doses of G100 when administered by intratumoral injection. The development of anti-tumor immune responses and preliminary evidence of clinical responses in local and distal tumor sites will also be examined.

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2 Study of Intratumoral G100 With Or Without Pembrolizumab or Rituximab In Patients With Follicular Non-Hodgkin's Lymphoma
Actual Study Start Date :
Feb 3, 2016
Actual Primary Completion Date :
Aug 1, 2019
Actual Study Completion Date :
Aug 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: Local Radiation + G100 5μg/tumor

Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks.

Drug: G100
GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    		•
    Experimental: Part 1: Local Radiation + G100 10μg/tumor

    Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks.

    Drug: G100
    GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
    Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    		•
    Experimental: Part 2: Local Radiation + G100 10μg/tumor

    Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks.

    Drug: G100
    GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
    Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    		•
    Experimental: Part 2: Local Radiation + G100 10μg/tumor+Pembrolizumab 200mg

    Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years.

    Drug: G100
    GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
    Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    • Drug: Pembrolizumab
    PD-1 Inhibitor
    Other Names:
  • Keytruda
  • MK-3475

    		•
    Experimental: Part 2: Local Radiation, G100 20 μg/tumor in Large Tumors

    Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors [injectable lymphoma mass(es) ≥ 4 cm in total size] for up to 8 weeks.

    Drug: G100
    GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
    Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    		•
    Experimental: Part 3: Local Radiation + G100 20μg/tumor

    Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks.

    Drug: G100
    GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
    Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    		•
    Experimental: Part 4: G100 20μg/tumor and pembrolizumab 200mg

    Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.

    Drug: G100
    GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
    Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    • Drug: Pembrolizumab
    PD-1 Inhibitor
    Other Names:
  • Keytruda
  • MK-3475

    		•
    Experimental: Part 5: G100 + Rituximab 375mg/m^2

    Part 5: G100 at 20, 40, 60, or 80μg/tumor administered IT for up to 6 weeks and rituximab administered as an IV infusion at 375mg/m^2 on Day 0 and then QW for up to 3 weeks.

    Drug: G100
    GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist
    Other Names:
  • glucopyranosyl lipid A stable emulsion, GLA-SE

    • Drug: Rituximab
    Rituximab (anti-CD20 antibody)

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With an Adverse Event (AE) [Up to approximately 42 months]

      An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    2. Number of Participants Who Discontinued Study Drug Due to an Adverse Event [Up to approximately 105 weeks]

      An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) by Immune-related Response Criteria (irRC) [Up to approximately 42 months]

      Overall response rate was defined as the number and percent of participants with best overall response of immune-related complete response (irCR) or immune-related partial response (irPR). irRC requires confirmatory restaging to determine if tumor size increase is due to true progression instead of immune inflammation and that new tumors add to tumor size calculations are not determinants of progressive disease by themselves. An immune-related Complete Response (irCR) is the disappearance of all tumors, measured or unmeasured, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a ≥25% increase in tumour burden from the lowest level recorded. Everything else is considered immune-related Stable Disease (irSD). Tumor staging using bi-dimensional measurements was performed by CT or MRI.

    2. Clinical Benefit Rate (CBR) Using Immune-related Response Criteria (irRC) [Up to approximately 42 months]

      Clinical benefit rate (CBR) was defined as the number and percent of participants with best overall response of complete response, partial response or stable disease (irCR+irPR+irSD). Clinical response was assessed by Immune-related Response Criteria (irRC) using bi-dimensional measurements as a preliminary indication of efficacy. irRC requires confirmatory restaging to determine if tumor size increase is due to true progression instead of immune inflammation and that new tumors add to tumor size calculations are not determinants of progressive disease by themselves. An immune-related Complete Response (irCR) is the disappearance of all tumors, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumor burden from baseline; and immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Everything else is considered immune-related Stable Disease (irSD). Tumor staging by CT or MRI was performed.

    3. Clinical Benefit Rate (CBR) Using International Working Group (IWG) Criteria [Up to approximately 42 months]

      Clinical benefit rate (CBR) will be defined as the number and percent of participants with best overall response of complete response, partial response or stable disease (CR+PR+SD). The IWG criteria (Cheson et al 2014) for a CR is a complete radiologic response (target nodes/nodal masses must regress to ≤1.5 cm in longest transverse diameter (LDi), no extralymphatic sites of disease, and no new tumors. A PR is a ≥50% decrease in SPD (sum of the product of the perpendicular diameters for multiple tumors) of up to 6 target measurable nodes and extranodal sites, spleen must have regressed by >50% in length beyond normal, and no new tumors. Stable disease is a <50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extranodal sites; no criteria for progressive disease are met, and no new tumors.

    4. Duration of Response (DOR) by Immune-related Response Criteria (irRC) [Up to approximately 42 months]

      Duration of response (DOR) was defined as the time interval between the date of the earliest qualifying confirmed/unconfirmed response using irRC and the date of disease progression (PD) or death for any cause, whichever occurs first. DOR in months was calculated as: (date of PD or death minus date of first confirmed/unconfirmed irCR/CR or irPR/PR + 1)/30.4375. DOR analysis included only participants with confirmed/unconfirmed response of irCR/irPR using irRC. Immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Summary of DOR including median was estimated using the Kaplan-Meier method in each treatment group.

    5. Duration of Clinical Benefit by Immune-related Response Criteria (irRC) [Up to approximately 42 months]

      Duration of clinical benefit was defined as the time interval between the date of the earliest qualifying confirmed/unconfirmed best response using irRC and the date of progression disease (PD) or death for any cause, whichever occurred first. Duration of clinical benefit in months was calculated as: (date of PD or death - date of first confirmed/unconfirmed irCR/irPR or irSD + 1)/30.4375. Duration of clinical benefit included only participants with confirmed/unconfirmed response of irCR/irPR or irSD using irRC. For participants who were alive without documentation of disease progression following the qualifying response, duration of clinical benefit was censored following the same rule defined for PFS. Summary of duration of clinical benefit including median was estimated using the Kaplan Meier method in each treatment group.

    6. Progression-free Survival (PFS) [Up to approximately 42 months]

      PFS was defined as time from date of first study treatment to date of first disease progression by irRC criteria, symptomatic deterioration, or death due to any cause, whichever occurs first. Progression-free survival in months is calculated as: (date of first progression, symptomatic deterioration, or death (any reason) - date of first dose +1)/30.4375. The irRC modification required a PD confirmation no less than 4 weeks from first documentation of PD; once confirmed, the date of progression was defined as date of the first PD. Participants without progression, symptomatic deterioration, or death were censored at the date of the last tumor assessment. Immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Summary of PFS including median was estimated using the Kaplan-Meier method in each treatment group.

    7. Overall Survival (OS) [Up to approximately 42 months]

      Overall Survival (OS) was defined as the time from date of first study treatment to death due to any cause. Overall survival in months was calculated as: (date of death - date of first dose) +1)/30.4375. Participants who were alive at the end of study were censored at the last date the participant was known to be alive or data analysis cutoff date, whichever was earlier. Summary of OS including median was estimated using the Kaplan-Meier method in each treatment group.

    8. Overall Tumor Response Based on irRC Abscopal Sites [Up to approximately 42 months]

      Abscopal tumor responses were assessed in non-treated, distal tumor sites. Clinical response was assessed by Immune-related Response Criteria (irRC) using bi-dimensional measurements as a preliminary indication of efficacy. irRC requires confirmatory restaging to determine if tumor size increase is due to true progression instead of immune inflammation and that new tumors add to tumor size calculations are not determinants of progressive disease by themselves. An immune-related Complete Response (irCR) is the disappearance of all tumors, measured or unmeasured, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a ≥25% increase in tumour burden from the lowest level recorded. Everything else was considered immune-related Stable Disease (irSD). Tumor staging by CT or MRI was performed.

    9. Time to Response for Complete Response and Partial Response Participants [Up to approximately 42 months]

      Time to Response for CR and PR participants was defined as time from date of first study treatment to the date of CR or PR response first documented. Complete Response (irCR) is the disappearance of all tumors, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumor burden from baseline. Time to response in months was calculated as: (date of first CR or PR minus date of first dose +1)/30.4375. Summary of Time to Response including median was estimated using Kaplan-Meier method in each treatment group.

    10. Time to Next Treatment (TTNT) [Up to approximately 42 months]

      Time to next treatment was defined as the time from the date of first study treatment to the start date of subsequent therapy after PD. Immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Participants who did not receive subsequent therapy after PD were censored at the date of last contact or death. Summary of TTNT including median was estimated using the Kaplan-Meier method in each treatment group.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Follicular low-grade NHL:

    • In Part 1-3: either treatment naïve (except for France) OR relapsed or refractory following at least one prior treatment.

    • In Part 4, enrollment is limited to relapsed OR refractory follicular NHL participants.

    • In Part 5, enrollment will include relapsed and refractory CD20+ follicular NHL following at least one but not more than 2 prior treatments.

    1. Tumor mass(es) accessible for intratumoral injection

    • For Part 1-3, are being considered for local radiation therapy and at least one additional site of disease outside the radiation field for assessment of distal (abscopal) response.

    • For Part 4 and 5, radiation therapy is omitted. Measurable tumor mass(es) accessible for intratumoral injection must be present for treatment and assessment of response.

    1. ≥ 18 years of age

    2. Life expectancy of ≥ 6 months per the investigator

    3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    4. Electrocardiogram (ECG) without evidence of clinically significant arrhythmia or ischemia

    5. If female of childbearing potential (FCBP), willing to undergo pregnancy testing and agrees to use two methods of birth control or is considered highly unlikely to conceive during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment

    6. If male and sexually active with a FCBP, must agree to use highly effective contraception such as latex condom or is sterile (e.g. following a surgical procedure) during the dosing period and for three months after last study treatment, or if receiving pembrolizumab, four months after last treatment

    Exclusion Criteria:

    1. Cancer therapies, including chemotherapy, radiation (non-study regimen related), biologics or kinase inhibitors, granulocyte-colony stimulating factor (G-CSF) or granulocyte/monocyte-colony stimulating factor (GM-CSF) within 4 weeks prior to the first scheduled G100 dose

    2. Investigational therapy within 4 weeks prior to G100 dosing

    3. Prior administration of other intratumoral immunotherapeutics

    4. Inadequate organ function including:

    5. Marrow: Peripheral blood leukocyte count (WBC) < 3000/mm3, absolute neutrophil count ≤ 1500/mm3, platelets < 75000/mm^3, or hemoglobin < 10 gm/dL

    6. Hepatic: alanine aminotransferase (ALT), and aspartate aminotransferase (AST) > 2.5 x Upper Limit of Normal (ULN), total serum bilirubin > 1.5 x ULN (participants with Gilbert's Disease may be included if their total bilirubin is ≤3.0 mg/dL)

    7. Renal: Creatinine > 1.5x ULN

    8. Other: INR (international normalized ratio) or partial thromboplastin time (PTT)

    1.5 x ULN

    1. Significant immunosuppression from:

    2. Concurrent, recent (≤ 4 weeks ago) or anticipated treatment with systemic corticosteroids at any dose, or

    3. Other immunosuppressive medications such as methotrexate, cyclosporine, azathioprine or conditions such as common variable hypogammaglobulinemia

    4. Pregnant or nursing

    5. Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure

    6. History of other cancer within 2 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ)

    7. Recent (<1 week ago) clinically significant infection, active tuberculosis or evidence of active hepatitis B, hepatitis C or HIV infection

    8. Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease.

    9. Significant autoimmune disease, including active non-infectious pneumonitis, with the exception of alopecia, vitiligo, hypothyroidism or other conditions that have never been clinically active or were transient and have completely resolved and require no ongoing therapy

    10. Psychiatric, other medical illness or other condition that in the opinion of the principal investigator (PI) prevents compliance with study procedures or ability to provide valid informed consent

    11. History of significant adverse or allergic reaction to any component of G100 and, if enrolled in Part 2 or Part 4, pembrolizumab and/or any of its excipients, and if enrolled in Part 5, anti-CD20 antibodies including rituximab and/or any of its excipients

    12. Use of anti-coagulant agents or history a significant bleeding diathesis. (If a superficial lymph node or subcutaneous mass is to be injected, participants on agents such as non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, or clopidogrel are eligible and these agents do not have to be withheld. For procedures with moderate or significant risk of bleeding, long-acting agents such as aspirin or clopidogrel should be discussed with the Medical Monitor and may need to be discontinued before G100 therapy.

    For participants enrolled in Part 2 or Part 4 with the potential to receive pembrolizumab:

    1. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis or interstitial lung disease

    2. Received a live virus vaccine within 30 days of planned study start

    3. Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of graft vs. host disease [GVHD]).

    4. Has had an allogeneic tissue/solid organ transplant

    5. Has received prior therapy with an anti-PD-1, anti-programmed death ligand (PD-L)1, or anti-PD-L2 agent or if the participant has previously participated in Merck MK-3475 clinical trials or was previously treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Immune Design
    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Lisa Knapp, Clinical Trial Manager

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Immune Design
    ClinicalTrials.gov Identifier:
    NCT02501473
    Other Study ID Numbers:
    • 3475-174
    • IMDZ-G142
    • MK-3475-174
    • 2015-005382-23
    First Posted:
    Jul 17, 2015
    Last Update Posted:
    Sep 9, 2020
    Last Verified:
    Aug 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Immune Design
    follicular lymphoma
    FL
    low-grade lymphoma
    Non-Hodgkin's Lymphoma
    follicular NHL
    Marginal Zone
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Non-Hodgkin
    Lymphoma, Follicular
    Rituximab
    Pembrolizumab

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled in the study at clinical sites in the United States and Europe.
    Pre-assignment Detail Part 5, G100 plus Rituximab, Dose Escalation: 12 to 24 participants were planned; no participant was enrolled or dosed.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg Part 5: G100 + Rituximab 375 mg/m^2
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years. Part 5: G100 administered at 20, 40, 60, or 80 μg/tumor for up to 6 weeks and rituximab (anti-CD20 antibody). Rituximab dose administered as an IV infusion at 375 mg/m^2 administered on Day 0 and then once weekly for 4 doses up to 3 weeks.
    Period Title: Overall Study
    STARTED 3 3 13 14 4 14 1 0
    Treated 3 3 13 13 4 14 1 0
    COMPLETED 0 0 0 0 0 0 0 0
    NOT COMPLETED 3 3 13 14 4 14 1 0

    Baseline Characteristics

    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg Total
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years. Total of all reporting groups
    Overall Participants 3 3 13 13 4 14 1 51
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    54.0
    (13.45)
    56.3
    (16.07)
    60.2
    (10.26)
    57.6
    (10.98)
    59.3
    (5.85)
    63.9
    (8.74)
    NA
    (NA)
    60.3
    (10.47)
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    2
    66.7%
    3
    23.1%
    3
    23.1%
    1
    25%
    5
    35.7%
    1
    100%
    16
    31.4%
    Male
    2
    66.7%
    1
    33.3%
    10
    76.9%
    10
    76.9%
    3
    75%
    9
    64.3%
    0
    0%
    35
    68.6%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    33.3%
    1
    7.7%
    3
    23.1%
    0
    0%
    0
    0%
    0
    0%
    5
    9.8%
    Not Hispanic or Latino
    2
    66.7%
    2
    66.7%
    12
    92.3%
    10
    76.9%
    4
    100%
    13
    92.9%
    1
    100%
    44
    86.3%
    Unknown or Not Reported
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    0
    0%
    2
    3.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    1
    2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    1
    7.7%
    0
    0%
    0
    0%
    1
    7.1%
    0
    0%
    2
    3.9%
    White
    2
    66.7%
    3
    100%
    11
    84.6%
    12
    92.3%
    2
    50%
    12
    85.7%
    1
    100%
    43
    84.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    33.3%
    0
    0%
    1
    7.7%
    1
    7.7%
    1
    25%
    1
    7.1%
    0
    0%
    5
    9.8%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With an Adverse Event (AE)
    Description An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants who received at least 1 injection of G100 after standard local radiation.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Count of Participants [Participants]
    3
    100%
    3
    100%
    13
    100%
    13
    100%
    4
    100%
    14
    100%
    1
    100%
    2. Primary Outcome
    Title Number of Participants Who Discontinued Study Drug Due to an Adverse Event
    Description An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
    Time Frame Up to approximately 105 weeks

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants who received at least 1 injection of G100 after standard local radiation.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    2
    15.4%
    0
    0%
    1
    7.1%
    0
    0%
    3. Secondary Outcome
    Title Overall Response Rate (ORR) by Immune-related Response Criteria (irRC)
    Description Overall response rate was defined as the number and percent of participants with best overall response of immune-related complete response (irCR) or immune-related partial response (irPR). irRC requires confirmatory restaging to determine if tumor size increase is due to true progression instead of immune inflammation and that new tumors add to tumor size calculations are not determinants of progressive disease by themselves. An immune-related Complete Response (irCR) is the disappearance of all tumors, measured or unmeasured, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a ≥25% increase in tumour burden from the lowest level recorded. Everything else is considered immune-related Stable Disease (irSD). Tumor staging using bi-dimensional measurements was performed by CT or MRI.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, and had baseline and at least 1 post-baseline disease assessment.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Complete Response (irCR)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Partial Response (irPR)
    1
    33.3%
    2
    66.7%
    3
    23.1%
    6
    46.2%
    1
    25%
    6
    42.9%
    0
    0%
    Stable Disease (irSD)
    2
    66.7%
    1
    33.3%
    8
    61.5%
    6
    46.2%
    3
    75%
    7
    50%
    1
    100%
    Progressive Disease (irPD)
    0
    0%
    0
    0%
    2
    15.4%
    1
    7.7%
    0
    0%
    1
    7.1%
    0
    0%
    4. Secondary Outcome
    Title Clinical Benefit Rate (CBR) Using Immune-related Response Criteria (irRC)
    Description Clinical benefit rate (CBR) was defined as the number and percent of participants with best overall response of complete response, partial response or stable disease (irCR+irPR+irSD). Clinical response was assessed by Immune-related Response Criteria (irRC) using bi-dimensional measurements as a preliminary indication of efficacy. irRC requires confirmatory restaging to determine if tumor size increase is due to true progression instead of immune inflammation and that new tumors add to tumor size calculations are not determinants of progressive disease by themselves. An immune-related Complete Response (irCR) is the disappearance of all tumors, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumor burden from baseline; and immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Everything else is considered immune-related Stable Disease (irSD). Tumor staging by CT or MRI was performed.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, and had baseline and at least 1 post-baseline disease assessment.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Number (95% Confidence Interval) [Percent of participants]
    100
    3333.3%
    100
    3333.3%
    84.6
    650.8%
    92.3
    710%
    100
    2500%
    92.9
    663.6%
    100
    10000%
    5. Secondary Outcome
    Title Clinical Benefit Rate (CBR) Using International Working Group (IWG) Criteria
    Description Clinical benefit rate (CBR) will be defined as the number and percent of participants with best overall response of complete response, partial response or stable disease (CR+PR+SD). The IWG criteria (Cheson et al 2014) for a CR is a complete radiologic response (target nodes/nodal masses must regress to ≤1.5 cm in longest transverse diameter (LDi), no extralymphatic sites of disease, and no new tumors. A PR is a ≥50% decrease in SPD (sum of the product of the perpendicular diameters for multiple tumors) of up to 6 target measurable nodes and extranodal sites, spleen must have regressed by >50% in length beyond normal, and no new tumors. Stable disease is a <50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extranodal sites; no criteria for progressive disease are met, and no new tumors.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, and had baseline and at least 1 post-baseline disease assessment.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Number (95% Confidence Interval) [Percentage of participants]
    100
    3333.3%
    100
    3333.3%
    84.6
    650.8%
    92.3
    710%
    100
    2500%
    78.6
    561.4%
    100
    10000%
    6. Secondary Outcome
    Title Duration of Response (DOR) by Immune-related Response Criteria (irRC)
    Description Duration of response (DOR) was defined as the time interval between the date of the earliest qualifying confirmed/unconfirmed response using irRC and the date of disease progression (PD) or death for any cause, whichever occurs first. DOR in months was calculated as: (date of PD or death minus date of first confirmed/unconfirmed irCR/CR or irPR/PR + 1)/30.4375. DOR analysis included only participants with confirmed/unconfirmed response of irCR/irPR using irRC. Immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Summary of DOR including median was estimated using the Kaplan-Meier method in each treatment group.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants who received at least 1 injection of G100 after standard local radiation and had a confirmed/unconfirmed response of irCR/irPR using irRC.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 1 1 3 4 1 5 0
    Median (Full Range) [Months]
    1.8
    15.6
    NA
    18.4
    NA
    5.6
    7. Secondary Outcome
    Title Duration of Clinical Benefit by Immune-related Response Criteria (irRC)
    Description Duration of clinical benefit was defined as the time interval between the date of the earliest qualifying confirmed/unconfirmed best response using irRC and the date of progression disease (PD) or death for any cause, whichever occurred first. Duration of clinical benefit in months was calculated as: (date of PD or death - date of first confirmed/unconfirmed irCR/irPR or irSD + 1)/30.4375. Duration of clinical benefit included only participants with confirmed/unconfirmed response of irCR/irPR or irSD using irRC. For participants who were alive without documentation of disease progression following the qualifying response, duration of clinical benefit was censored following the same rule defined for PFS. Summary of duration of clinical benefit including median was estimated using the Kaplan Meier method in each treatment group.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants who received at least 1 injection of G100 after standard local radiation and had a confirmed/unconfirmed response of irCR/irPR or irSD using irRC.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 11 12 4 13 0
    Median (Full Range) [Months]
    2.5
    20.8
    6.9
    9.2
    7.2
    4.3
    8. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description PFS was defined as time from date of first study treatment to date of first disease progression by irRC criteria, symptomatic deterioration, or death due to any cause, whichever occurs first. Progression-free survival in months is calculated as: (date of first progression, symptomatic deterioration, or death (any reason) - date of first dose +1)/30.4375. The irRC modification required a PD confirmation no less than 4 weeks from first documentation of PD; once confirmed, the date of progression was defined as date of the first PD. Participants without progression, symptomatic deterioration, or death were censored at the date of the last tumor assessment. Immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Summary of PFS including median was estimated using the Kaplan-Meier method in each treatment group.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, and had baseline and at least 1 post-baseline disease assessment.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Median (Full Range) [Months]
    4.9
    22.6
    7.4
    11.1
    9.8
    7.7
    NA
    9. Secondary Outcome
    Title Overall Survival (OS)
    Description Overall Survival (OS) was defined as the time from date of first study treatment to death due to any cause. Overall survival in months was calculated as: (date of death - date of first dose) +1)/30.4375. Participants who were alive at the end of study were censored at the last date the participant was known to be alive or data analysis cutoff date, whichever was earlier. Summary of OS including median was estimated using the Kaplan-Meier method in each treatment group.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, and had baseline and at least 1 post-baseline disease assessment.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Median (Full Range) [Months]
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    10. Secondary Outcome
    Title Overall Tumor Response Based on irRC Abscopal Sites
    Description Abscopal tumor responses were assessed in non-treated, distal tumor sites. Clinical response was assessed by Immune-related Response Criteria (irRC) using bi-dimensional measurements as a preliminary indication of efficacy. irRC requires confirmatory restaging to determine if tumor size increase is due to true progression instead of immune inflammation and that new tumors add to tumor size calculations are not determinants of progressive disease by themselves. An immune-related Complete Response (irCR) is the disappearance of all tumors, measured or unmeasured, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a ≥25% increase in tumour burden from the lowest level recorded. Everything else was considered immune-related Stable Disease (irSD). Tumor staging by CT or MRI was performed.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, and had baseline and at least 1 post-baseline disease assessment.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 3 13 13 4 14 1
    Complete Response (irCR)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Partial Response (irPR)
    0
    0%
    1
    33.3%
    4
    30.8%
    3
    23.1%
    0
    0%
    3
    21.4%
    0
    0%
    Stable Disease (irSD)
    1
    33.3%
    2
    66.7%
    4
    30.8%
    8
    61.5%
    3
    75%
    9
    64.3%
    1
    100%
    Progressive Disease (irPD)
    1
    33.3%
    0
    0%
    4
    30.8%
    2
    15.4%
    1
    25%
    2
    14.3%
    0
    0%
    11. Secondary Outcome
    Title Time to Response for Complete Response and Partial Response Participants
    Description Time to Response for CR and PR participants was defined as time from date of first study treatment to the date of CR or PR response first documented. Complete Response (irCR) is the disappearance of all tumors, and no new tumors; an immune-related Partial Response (irPR) is a ≥50% drop in tumor burden from baseline. Time to response in months was calculated as: (date of first CR or PR minus date of first dose +1)/30.4375. Summary of Time to Response including median was estimated using Kaplan-Meier method in each treatment group.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, had baseline and at least 1 post-baseline disease assessment, and had a best response of CR or PR.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 1 2 3 6 1 6 0
    Median (Full Range) [Months]
    1.9
    1.9
    2.3
    4.1
    2.6
    5.2
    12. Secondary Outcome
    Title Time to Next Treatment (TTNT)
    Description Time to next treatment was defined as the time from the date of first study treatment to the start date of subsequent therapy after PD. Immune-related Progressive Disease (irPD) is a ≥25% increase in tumor burden from the lowest level recorded. Participants who did not receive subsequent therapy after PD were censored at the date of last contact or death. Summary of TTNT including median was estimated using the Kaplan-Meier method in each treatment group.
    Time Frame Up to approximately 42 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants without major protocol deviations, who received at least 1 injection of G100, had baseline and at least 1 post-baseline disease assessment, and had subsequent therapy with PD.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    Measure Participants 3 1 8 6 1 6 0
    Median (Full Range) [Months]
    5.4
    NA
    12.7
    NA
    NA
    NA

    Adverse Events

    Time Frame Up to approximately 42 months
    Adverse Event Reporting Description The analysis population included all enrolled and treated participants. Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered treatment-related. Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment were excluded as AEs. Part 5, G100 plus Rituximab, Dose Escalation: no participant was enrolled or dosed.
    Arm/Group Title Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Arm/Group Description Part 1: Local radiation and G100 [glucopyranosyl lipid A stable emulsion, GLA-SE] at 5μg/tumor administered intratumorally (IT) into accessible tumors for up to 8 weeks. Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks; pembrolizumab 200mg intravenously (IV) administered every 3 weeks (Q3W) IV for up to 2 years. Part 2: Local radiation and G100 at 20 μg/tumor administered IT into accessible large tumors (injectable lymphoma mass(es) ≥ 4 cm in total size) for up to 8 weeks. Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. Part 4: G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks and pembrolizumab 200mg IV and administered Q3W for up to 2 years.
    All Cause Mortality
    Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/3 (0%) 1/13 (7.7%) 1/14 (7.1%) 0/4 (0%) 1/14 (7.1%) 0/1 (0%)
    Serious Adverse Events
    Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/3 (0%) 1/13 (7.7%) 4/13 (30.8%) 0/4 (0%) 0/14 (0%) 0/1 (0%)
    Endocrine disorders
    Adrenal insufficiency 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Gastrointestinal disorders
    Abdominal pain upper 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    General disorders
    Pyrexia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Infections and infestations
    Septic shock 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Injury, poisoning and procedural complications
    Multiple fractures 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Other (Not Including Serious) Adverse Events
    Part 1: Local Radiation + G100 5μg/Tumor Part 1: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor Part 2: Local Radiation + G100 10μg/Tumor+Pembrolizumab 200mg Part 2: Local Radiation, G100 20 μg/Tumor in Large Tumors Part 3: Local Radiation + G100 20μg/Tumor Part 4: G100 20μg/Tumor and Pembrolizumab 200mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 13/13 (100%) 13/13 (100%) 4/4 (100%) 14/14 (100%) 1/1 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/3 (33.3%) 1 0/3 (0%) 0 1/13 (7.7%) 2 2/13 (15.4%) 3 1/4 (25%) 4 0/14 (0%) 0 0/1 (0%) 0
    Blood loss anaemia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Leukocytosis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Leukopenia 0/3 (0%) 0 1/3 (33.3%) 1 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Lymph node pain 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Cardiac disorders
    Coronary artery disease 0/3 (0%) 0 1/3 (33.3%) 1 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Myocardial fibrosis 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Sinus bradycardia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Tachycardia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Ear and labyrinth disorders
    Ear congestion 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Tinnitus 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Vertigo 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 1/14 (7.1%) 2 0/1 (0%) 0
    Endocrine disorders
    Hyperthyroidism 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hypothyroidism 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Eye disorders
    Diplopia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Eyelid ptosis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Periorbital oedema 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Vision blurred 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 2 0/1 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 1/3 (33.3%) 1 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Abdominal distension 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 1/14 (7.1%) 1 0/1 (0%) 0
    Abdominal pain 1/3 (33.3%) 1 0/3 (0%) 0 1/13 (7.7%) 2 2/13 (15.4%) 4 2/4 (50%) 3 2/14 (14.3%) 2 0/1 (0%) 0
    Colitis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Constipation 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 2 1/4 (25%) 2 1/14 (7.1%) 1 0/1 (0%) 0
    Dental caries 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Diarrhoea 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 2 4/13 (30.8%) 4 0/4 (0%) 0 2/14 (14.3%) 2 0/1 (0%) 0
    Dyspepsia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Dysphagia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Flatulence 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Hiatus hernia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hypoaesthesia oral 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Inguinal hernia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Nausea 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 2 6/13 (46.2%) 7 1/4 (25%) 2 3/14 (21.4%) 4 0/1 (0%) 0
    Rectal tenesmus 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Toothache 2/3 (66.7%) 2 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Vomiting 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 3/13 (23.1%) 3 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    General disorders
    Administration site pain 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Asthenia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 4/13 (30.8%) 7 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Chest pain 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 2/13 (15.4%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Chills 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/4 (0%) 0 3/14 (21.4%) 3 0/1 (0%) 0
    Fatigue 1/3 (33.3%) 1 2/3 (66.7%) 2 0/13 (0%) 0 4/13 (30.8%) 4 2/4 (50%) 2 3/14 (21.4%) 3 1/1 (100%) 1
    Feeling hot 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Influenza like illness 0/3 (0%) 0 1/3 (33.3%) 2 0/13 (0%) 0 2/13 (15.4%) 2 0/4 (0%) 0 2/14 (14.3%) 2 0/1 (0%) 0
    Infusion site swelling 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Injection site bruising 1/3 (33.3%) 1 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Injection site discomfort 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Injection site erythema 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 2/14 (14.3%) 2 0/1 (0%) 0
    Injection site pain 0/3 (0%) 0 0/3 (0%) 0 3/13 (23.1%) 5 1/13 (7.7%) 1 0/4 (0%) 0 2/14 (14.3%) 3 0/1 (0%) 0
    Injection site reaction 0/3 (0%) 0 1/3 (33.3%) 1 1/13 (7.7%) 5 2/13 (15.4%) 4 0/4 (0%) 0 1/14 (7.1%) 8 0/1 (0%) 0
    Injection site swelling 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Oedema peripheral 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Pain 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 3/14 (21.4%) 3 0/1 (0%) 0
    Peripheral swelling 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Pyrexia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 1/4 (25%) 4 2/14 (14.3%) 2 0/1 (0%) 0
    Immune system disorders
    Drug hypersensitivity 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Seasonal allergy 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Infections and infestations
    Candida infection 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Cellulitis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Conjunctivitis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Diverticulitis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Helicobacter duodenitis 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Herpes virus infection 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Influenza 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Nasopharyngitis 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 2/13 (15.4%) 3 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Oesophagitis bacterial 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Oral herpes 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Rhinovirus infection 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Sinusitis 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 3 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Tooth infection 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Upper respiratory tract infection 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 5 2/13 (15.4%) 2 1/4 (25%) 1 1/14 (7.1%) 1 0/1 (0%) 0
    Urinary tract infection 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 3 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Expired product administered 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 3 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Fall 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Procedural pain 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Radiation associated pain 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Radiation skin injury 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Skin laceration 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/3 (0%) 0 1/3 (33.3%) 1 1/13 (7.7%) 1 3/13 (23.1%) 5 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Aspartate aminotransferase increased 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 2 2/13 (15.4%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Blast cell count increased 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Blood alkaline phosphatase increased 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 2 2/13 (15.4%) 5 1/4 (25%) 2 0/14 (0%) 0 0/1 (0%) 0
    Blood bilirubin decreased 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Blood bilirubin increased 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 2 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 5 0/1 (0%) 0
    Blood creatinine decreased 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Blood creatinine increased 0/3 (0%) 0 1/3 (33.3%) 1 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 2/14 (14.3%) 3 0/1 (0%) 0
    Blood glucose increased 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Breath sounds abnormal 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Haemoglobin increased 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Lymphocyte count decreased 0/3 (0%) 0 1/3 (33.3%) 1 2/13 (15.4%) 3 0/13 (0%) 0 1/4 (25%) 1 3/14 (21.4%) 6 0/1 (0%) 0
    Neutrophil count decreased 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 2 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 2 0/1 (0%) 0
    Platelet count decreased 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 2 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    White blood cell count decreased 0/3 (0%) 0 1/3 (33.3%) 1 2/13 (15.4%) 4 1/13 (7.7%) 1 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hyperglycaemia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 3 3/13 (23.1%) 5 0/4 (0%) 0 1/14 (7.1%) 2 0/1 (0%) 0
    Hyperkalaemia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 7 2/14 (14.3%) 2 0/1 (0%) 0
    Hyperlipidaemia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Hypernatraemia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hyperuricaemia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 2 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hypoalbuminaemia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hypocalcaemia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hypokalaemia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Hyponatraemia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 2/13 (15.4%) 3 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 3/13 (23.1%) 3 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Back pain 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 2 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Bone pain 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Flank pain 1/3 (33.3%) 1 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Gouty arthritis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Groin pain 0/3 (0%) 0 1/3 (33.3%) 1 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Muscle spasms 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Musculoskeletal chest pain 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Musculoskeletal pain 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Myalgia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 2/13 (15.4%) 2 0/4 (0%) 0 2/14 (14.3%) 3 0/1 (0%) 0
    Pain in extremity 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 2 2/4 (50%) 2 0/14 (0%) 0 0/1 (0%) 0
    Plantar fasciitis 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Nervous system disorders
    Carpal tunnel syndrome 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Dizziness 0/3 (0%) 0 1/3 (33.3%) 1 1/13 (7.7%) 1 2/13 (15.4%) 3 0/4 (0%) 0 2/14 (14.3%) 3 0/1 (0%) 0
    Dysgeusia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Headache 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Neuropathy peripheral 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Nystagmus 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Presyncope 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Psychiatric disorders
    Depression 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Insomnia 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 1/14 (7.1%) 1 0/1 (0%) 0
    Libido decreased 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Restlessness 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Sleep disorder 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Renal and urinary disorders
    Dysuria 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hydronephrosis 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Urinary hesitation 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Reproductive system and breast disorders
    Epididymal cyst 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Oedema genital 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Testicular atrophy 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Testis discomfort 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Vulvovaginal inflammation 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Cough 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 2 4/13 (30.8%) 5 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Dyspnoea 1/3 (33.3%) 1 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Nasal congestion 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 2 2/13 (15.4%) 4 0/4 (0%) 0 1/14 (7.1%) 1 1/1 (100%) 1
    Oropharyngeal pain 0/3 (0%) 0 0/3 (0%) 0 4/13 (30.8%) 4 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Pleural effusion 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Productive cough 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Pulmonary congestion 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Sinus congestion 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Throat irritation 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Upper-airway cough syndrome 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 3 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Dry skin 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Ecchymosis 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 1/1 (100%) 1
    Erythema 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 2 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hyperhidrosis 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 2/14 (14.3%) 4 0/1 (0%) 0
    Night sweats 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Pruritus 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Rash 0/3 (0%) 0 0/3 (0%) 0 2/13 (15.4%) 3 3/13 (23.1%) 5 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Rash papular 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Skin discolouration 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Skin hyperpigmentation 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Skin reaction 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Skin swelling 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Skin texture abnormal 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Vascular disorders
    Diastolic hypertension 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Embolism 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Flushing 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Haematoma 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Hot flush 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/4 (25%) 1 0/14 (0%) 0 0/1 (0%) 0
    Hypertension 0/3 (0%) 0 0/3 (0%) 0 1/13 (7.7%) 2 2/13 (15.4%) 4 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0
    Hypotension 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Systolic hypertension 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/4 (0%) 0 0/14 (0%) 0 0/1 (0%) 0
    Varicose vein 0/3 (0%) 0 0/3 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/4 (0%) 0 1/14 (7.1%) 1 0/1 (0%) 0

    Limitations/Caveats

    The study was terminated (halted prematurely) for business reasons.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Sponsor will have 30 days for review/ comment on any manuscripts from results of this clinical trial, and can request an additional 30 days in order to protect the Sponsor's confidential, proprietary data, and intellectual property rights. Abstracts, press releases, and other media presentations must also be forwarded to the Sponsor prior to release. No publication, manuscript, or other form of public disclosure shall contain any of the Sponsor's confidential/ proprietary information.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Immune Design
    ClinicalTrials.gov Identifier:
    NCT02501473
    Other Study ID Numbers:
    • 3475-174
    • IMDZ-G142
    • MK-3475-174
    • 2015-005382-23
    First Posted:
    Jul 17, 2015
    Last Update Posted:
    Sep 9, 2020
    Last Verified:
    Aug 1, 2020