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| ID | Type | Description | Link |
|---|---|---|---|
| IMDZ-G142 | Other Identifier | Immune Design Protocol Number | |
| MK-3475-174 | Other Identifier | Merck Protocol Number | |
| 2015-005382-23 | EudraCT Number |
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Business reasons
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Local Radiation + G100 5μg/tumor | Experimental | 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 + G100 10μg/tumor | Experimental | Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. |
|
| Part 2: Local Radiation + G100 10μg/tumor | Experimental | Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. |
|
| Part 2: Local Radiation + G100 10μg/tumor+Pembrolizumab 200mg | Experimental | 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. |
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| Part 2: Local Radiation, G100 20 μg/tumor in Large Tumors | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| G100 | Drug | GLA is a fully synthetic toll-like receptor-4 (TLR4) agonist |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With an Adverse Event (AE) | 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. | Up to approximately 42 months |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 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. | Up to approximately 105 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) by Immune-related Response Criteria (irRC) | 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. |
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Inclusion Criteria:
Follicular low-grade NHL:
Tumor mass(es) accessible for intratumoral injection
≥ 18 years of age
Life expectancy of ≥ 6 months per the investigator
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Electrocardiogram (ECG) without evidence of clinically significant arrhythmia or ischemia
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
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:
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
Investigational therapy within 4 weeks prior to G100 dosing
Prior administration of other intratumoral immunotherapeutics
Inadequate organ function including:
Significant immunosuppression from:
Pregnant or nursing
Myocardial infarction within 6 months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
History of other cancer within 2 years (except non-melanoma cutaneous malignancies and cervical carcinoma in situ)
Recent (<1 week ago) clinically significant infection, active tuberculosis or evidence of active hepatitis B, hepatitis C or HIV infection
Central nervous system involvement with lymphoma, including parenchymal and leptomeningeal disease.
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
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
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
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:
History of (non-infectious) pneumonitis that required steroids or has current pneumonitis or interstitial lung disease
Received a live virus vaccine within 30 days of planned study start
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]).
Has had an allogeneic tissue/solid organ transplant
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.
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| Name | Affiliation | Role |
|---|---|---|
| Lisa Knapp | Clinical Trial Manager | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34865586 | Derived | Halwani AS, Panizo C, Isufi I, Herrera AF, Okada CY, Cull EH, Kis B, Chaves JM, Bartlett NL, Ai W, de la Cruz-Merino L, Bryan LJ, Houot R, Linton K, Briones J, Chau I, von Keudell GR, Lu H, Yakovich A, Chen M, Meulen Jh T, Yurasov S, Hsu FJ, Flowers CR. Phase 1/2 study of intratumoral G100 (TLR4 agonist) with or without pembrolizumab in follicular lymphoma. Leuk Lymphoma. 2022 Apr;63(4):821-833. doi: 10.1080/10428194.2021.2010057. Epub 2021 Dec 6. |
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Part 5, G100 plus Rituximab, Dose Escalation: 12 to 24 participants were planned; no participant was enrolled or dosed.
Participants were enrolled in the study at clinical sites in the United States and Europe.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Part 1: Local Radiation + G100 10μg/Tumor |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 15, 2018 | Jul 21, 2020 |
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| Part 3: Local Radiation + G100 20μg/tumor | Experimental | Part 3: Local radiation and G100 at 20μg/tumor administered IT into accessible tumors for up to 8 weeks. |
|
| Part 4: G100 20μg/tumor and pembrolizumab 200mg | Experimental | 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 + Rituximab 375mg/m^2 | Experimental | 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. |
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| Pembrolizumab | Drug | PD-1 Inhibitor |
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| Rituximab | Drug | Rituximab (anti-CD20 antibody) |
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| Up to approximately 42 months |
| Clinical Benefit Rate (CBR) Using Immune-related Response Criteria (irRC) | 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. | Up to approximately 42 months |
| Clinical Benefit Rate (CBR) Using International Working Group (IWG) Criteria | 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. | Up to approximately 42 months |
| Duration of Response (DOR) by Immune-related Response Criteria (irRC) | 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. | Up to approximately 42 months |
| Duration of Clinical Benefit by Immune-related Response Criteria (irRC) | 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. | Up to approximately 42 months |
| Progression-free Survival (PFS) | 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. | Up to approximately 42 months |
| Overall Survival (OS) | 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. | Up to approximately 42 months |
| Overall Tumor Response Based on irRC Abscopal Sites | 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. | Up to approximately 42 months |
| Time to Response for Complete Response and Partial Response Participants | 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. | Up to approximately 42 months |
| Time to Next Treatment (TTNT) | 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. | Up to approximately 42 months |
Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| FG007 | Part 5: G100 + Rituximab 375 mg/m^2 | 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. |
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| COMPLETED |
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| NOT COMPLETED |
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The analysis population included all randomized and treated participants. Part 5, G100 plus Rituximab, Dose Escalation: 12 to 24 participants were planned; no participant was enrolled or dosed.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | 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. |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With an Adverse Event (AE) | 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. | The analysis population included all enrolled participants who received at least 1 injection of G100 after standard local radiation. | Posted | Count of Participants | Participants | Up to approximately 42 months |
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| Primary | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 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. | The analysis population included all enrolled participants who received at least 1 injection of G100 after standard local radiation. | Posted | Count of Participants | Participants | Up to approximately 105 weeks |
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| Secondary | Overall Response Rate (ORR) by Immune-related Response Criteria (irRC) | 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. | 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. | Posted | Count of Participants | Participants | Up to approximately 42 months |
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| Secondary | Clinical Benefit Rate (CBR) Using Immune-related Response Criteria (irRC) | 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. | 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. | Posted | Number | 95% Confidence Interval | Percent of participants | Up to approximately 42 months |
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| Secondary | Clinical Benefit Rate (CBR) Using International Working Group (IWG) Criteria | 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to approximately 42 months |
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| Secondary | Duration of Response (DOR) by Immune-related Response Criteria (irRC) | 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. | 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. | Posted | Median | Full Range | Months | Up to approximately 42 months |
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| Secondary | Duration of Clinical Benefit by Immune-related Response Criteria (irRC) | 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. | 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. | Posted | Median | Full Range | Months | Up to approximately 42 months |
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| Secondary | Progression-free Survival (PFS) | 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. | 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. | Posted | Median | Full Range | Months | Up to approximately 42 months |
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| Secondary | Overall Survival (OS) | 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. | 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. | Posted | Median | Full Range | Months | Up to approximately 42 months |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Tumor Response Based on irRC Abscopal Sites | 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. | 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. | Posted | Count of Participants | Participants | Up to approximately 42 months |
| ||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Response for Complete Response and Partial Response Participants | 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. | 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. | Posted | Median | Full Range | Months | Up to approximately 42 months |
| |||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Next Treatment (TTNT) | 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. | 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. | Posted | Median | Full Range | Months | Up to approximately 42 months |
|
Up to approximately 42 months
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG001 | 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. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG002 | 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. | 1 | 13 | 1 | 13 | 13 | 13 |
| EG003 | 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. | 1 | 14 | 4 | 13 | 13 | 13 |
| EG004 | 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. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG005 | 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. | 1 | 14 | 0 | 14 | 14 | 14 |
| EG006 | 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. | 0 | 1 | 0 | 1 | 1 | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adrenal insufficiency | Endocrine disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Multiple fractures | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blood loss anaemia | Blood and lymphatic system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Lymph node pain | Blood and lymphatic system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Myocardial fibrosis | Cardiac disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Ear congestion | Ear and labyrinth disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Eyelid ptosis | Eye disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Rectal tenesmus | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Administration site pain | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Infusion site swelling | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Injection site bruising | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Injection site discomfort | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Helicobacter duodenitis | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Herpes virus infection | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Oesophagitis bacterial | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Rhinovirus infection | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
| |
| Expired product administered | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
| |
| Radiation associated pain | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA Version 22.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blast cell count increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blood bilirubin decreased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blood creatinine decreased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Breath sounds abnormal | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Haemoglobin increased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA Version 22.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Gouty arthritis | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Plantar fasciitis | Musculoskeletal and connective tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Carpal tunnel syndrome | Nervous system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Nystagmus | Nervous system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Libido decreased | Psychiatric disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Restlessness | Psychiatric disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Urinary hesitation | Renal and urinary disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Epididymal cyst | Reproductive system and breast disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Oedema genital | Reproductive system and breast disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Testicular atrophy | Reproductive system and breast disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Testis discomfort | Reproductive system and breast disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Vulvovaginal inflammation | Reproductive system and breast disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Skin swelling | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Skin texture abnormal | Skin and subcutaneous tissue disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Diastolic hypertension | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Systolic hypertension | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
| |
| Varicose vein | Vascular disorders | MedDRA Version 22.0 | Systematic Assessment |
|
The study was terminated (halted prematurely) for business reasons.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 17, 2019 | Jul 21, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000706812 | TLR4 agonist G100 |
| C582435 | pembrolizumab |
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
|
|
Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
|
|
| 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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks.
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks.
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks.
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks.
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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Part 1: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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| 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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Part 2: Local radiation and G100 at 10μg/tumor administered IT into accessible tumors for up to 8 weeks.
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
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