Advanced Solid Tumors
Conditions
Keywords
Advanced tumor, Intratumoral injection, Intralesional injection
Brief summary
This is a Phase I/II multicenter, first-in-human open-label, dose escalation study to evaluate the safety, tolerability, and anti-tumor activity of intratumoral (IT)/intralesional (IL) injections of MK-4621 (RGT100) in adult participants with selected advanced or recurrent tumors.
Interventions
DRUGMK-4621
IT/IL injection Fixed concentration of 0.2 mg/mL Starting dose: 0.2 mg
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study was to be conducted in 2 groups: * Group A: participants with transdermally/transmucosally injectable tumors, and * Group B: participants with injectable liver tumors or liver metastases. However, Group B was not started.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥18 years 2. Participants with histologically or cytologically confirmed diagnosis of advanced or recurrent tumors (including lymphomas) for whom all standard treatments have been used or are not feasible and MK-4621 (RGT100) is a suitable treatment option and: 1. For Group A: has cutaneous, sub-cutaneous (SC), or lymph node injectable tumors 2. For Group B: has injectable liver tumors or liver metastases 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 4. Life expectancy \>3 months as assessed by the Investigator 5. Adequate organ function 6. Negative serum pregnancy test within 2 weeks before first dose of study drug if the participant is a woman of childbearing potential. Participants and participant's partners of childbearing potential must agree to use birth control consistently and correctly during the study and for at least 6 months after the last study drug application. 7. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and 1 separate injectable lesion with diameter ≥1 cm but \<7 cm 8. Ability to provide written informed consent before any study drug-related screening procedures being performed
Exclusion criteria
1. Any tumor-directed therapy within 4 weeks before study treatment 2. Treatment with investigational drugs within 4 weeks before study enrolment 3. Systemic steroids at a dose of \>10 mg of prednisolone, \>2 mg of dexamethasone a day or equivalent, except topical (inhaled, topical, nasal) for the last 28 days and ongoing 4. Participants with rapidly progressing disease (as determined by the Investigator) 5. Ongoing immune-related adverse events (irAEs) and/or adverse events (AEs) ≥ grade 2 not resolved from previous therapies except vitiligo, stable neuropathy grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy 6. Within 4 weeks of major surgery 7. Prior splenectomy 8. Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy 9. Primary or secondary immune deficiency 10. Active allergy requiring systemic medication or active infections requiring anti-infectious therapy 11. Seropositive (except after vaccination) for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) 12. Clinically significant cardiac disease including heart failure (New York Heart Association, Class III or IV), pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year before study entry 13. Dementia or altered mental status that would prohibit informed consent 14. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator 15. History of stroke, seizures, encephalitis, or multiple sclerosis 16. Gastric ulcer or inflammatory bowel disease or Crohn's disease or ulcerative colitis in the last 6 months 17. Active drug or alcohol abuse 18. Pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Up to 90 days post last injection (Up to approximately 192 days) | An AE was defined as any untoward medical occurrence in a study participant administered study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a Possible or Related relationship to study treatment, as assessed by the Investigator. Severity of AE referred to the extent to which an AE affected the participants daily activities as assessed by the Investigator and was based on NCI CTCAE grades: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe or medically significant but not immediately life-threatening); Grade 4 (Life-threatening consequences); or Grade 5 (Death related to AE). The number of participants who experienced at least one treatment-related AE or laboratory abnormality are presented by severity. |
| Number of Participants Who Experienced a Serious Adverse Event (SAE) | Up to 90 days post last injection (Up to approximately 192 days) | A SAE was defined as any AE, regardless of dose, causality or expectedness, that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolonged existing inpatient hospitalization; * Resulted in persistent or significant incapacity or disability; * Was a congenital anomaly or birth defect; or * Was any other medically important event. |
| Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE) | Up to last injection (Up to approximately 102 days) | An AE was defined as any untoward medical occurrence in a study participant administered a study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a Possible or Related relationship to study treatment, as assessed by the Investigator. The number of participants who discontinued study treatment due to a treatment-related AE is presented. |
| Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Cycle 1 (Up to approximately 28 days); Each cycle was 28 days. | DLTs were assessed during the first treatment cycle (28 days) & were defined as any drug-related toxicity that occurred during the 28-day DLT period and included: * Non-hematologic toxicity grade ≥3 (except diarrhea, nausea, and vomiting unless lasting \>3 days despite optimal supportive care); * Confirmed (with a second measurement after 24 hours) non-hematologic appropriately graded laboratory findings of Grade ≥3 that were ≤ Grade 1 at baseline; * Hematologic toxicity: * Grade 4 neutropenia ≥5 days, or Grade 3 neutropenia with fever (fever is \>38.4ºC) * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia lasting \>7 days or with bleeding; and * Any other toxicity assessed as related to MK-4621, and which, in the opinion of the Investigator and the Sponsor physician constituted a DLT. The number of participants who experienced a DLT is presented by NCI CTCAE version 4.03 severity grade. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Up to 60 days post last injection (Up to approximately 162 days) | ORR was defined as the percentage of participants who had a Complete Response (CR) or a Partial Response. Per irRECIST, CR (irCR) was defined as the complete disappearance of all measurable and non-measurable lesions. Lymph nodes must also have decreased to \<0 mm in short axis. And, per irRECIST, Partial Response (irPR) was defined as a decrease of ≥30% in total measured tumor burden (TMTB) relative to baseline. For this study, irRECIST was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced an irCR or irPR based on irRECIST is presented. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1 | Cycle 1 Day 1: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 2 days); Each cycle was 28 days. | Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 AUC0-t on Day 1, which was defined as the AUC from the start time of dosing to the time of the last observed concentration above the limit of quantitation (LOQ). |
| Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25 | Cycle 1 Day 25: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 26 days); Each cycle was 28 days. | Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 AUC0-t on Day 25, which was defined as the AUC from the start time of dosing to the time of the last observed concentration above the limit of quantitation (LOQ). |
| Maximum Plasma Concentration (Cmax) of MK-4621: Day 1 | Cycle 1 Day 1: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 2 days); Each cycle was 28 days. | Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 Cmax on Day 1. |
| Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | Day 1 prior to injection (Up to 1 day) | Sequential participant tumor biopsies were assessed via immunohistochemistry for the presence of tumor infiltrating CD3 T cell co-receptor-marked cells and Ki-67 nuclear protein-marked cells in tumor biopsies. CD3 is a marker of T cells and KI-67 is a cell marker of proliferation and activation. The percentage of positive CD3-marked cells and double-positive CD3 and Ki-67 nuclear protein-marked cells in tumor biopsies predose on Day 1 are presented. |
| Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | Day 25 post injection (Up to 25 days) | Sequential participant tumor biopsies were assessed via immunohistochemistry for the presence of tumor infiltrating CD3 T cell co-receptor-marked cells and Ki-67 nuclear protein-marked cells in tumor biopsies. CD3 is a marker of T cells and KI-67 is a cell marker of proliferation and activation. The percentage of positive CD3-marked cells and double-positive CD3 and Ki-67 nuclear protein-marked cells in tumor biopsies postdose on Day 25 are presented. |
| Maximum Plasma Concentration (Cmax) of MK-4621: Day 25 | Cycle 1 Day 25: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 26 days); Each cycle was 28 days. | Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 Cmax on Day 25. |
| Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | Baseline and Cycle 1 Day 1 (6 hours post injection) (Up to 1 day); Each cycle was 28 days. | Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma. |
| Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | Baseline and Cycle 1 Day 1 (24 hours post injection) (Up to 2 days); Each cycle was 28 days. | Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma. |
| Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | Baseline and Cycle 1 Day 25 (6 hours post injection) (Up to 25 days); Each cycle was 28 days. | Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma. |
| Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | Baseline and Cycle 1 Day 25 (24 hours post injection) (Up to 26 days); Each cycle was 28 days. | Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma. |
Countries
Germany, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: MK-4621 0.2 mg Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.2.mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator's assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days. | 3 |
| Group A: MK-4621 0.4 mg Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.4 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator's assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days. | 3 |
| Group A: MK-4621 0.6 mg Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.6 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator's assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days. | 3 |
| Group A: MK-4621 0.8 mg Participants with transdermally/transmucosally injectable tumors including cutaneous, subcutaneous or lymph node injectable tumors received MK-4621 0.8 mg via IT/IL injection twice each week over a period of 4 weeks during Cycle 1. Participants may have continued to receive study treatment beyond Cycle 1 for the remaining duration of the study as long as clinical benefit (no overt clinical progression or toxicity considered to be intolerable as per Investigator's assessment) was present (could have been up to approximately 2 years). Each cycle was 28 days. | 6 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Participant Decision | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Group A: MK-4621 0.2 mg | Total | Group A: MK-4621 0.8 mg | Group A: MK-4621 0.6 mg | Group A: MK-4621 0.4 mg |
|---|---|---|---|---|---|
| Age, Continuous | 51.7 Years STANDARD_DEVIATION 26.8 | 56.8 Years STANDARD_DEVIATION 15.9 | 64.2 Years STANDARD_DEVIATION 8.3 | 55.3 Years STANDARD_DEVIATION 16 | 48.7 Years STANDARD_DEVIATION 18.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 15 Participants | 6 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Plasma Cytokine Release by Cytokine Type IL-6 | 9.3 ng/L | 9.3 ng/L | 7.5 ng/L | 10 ng/L | 9.3 ng/L |
| Plasma Cytokine Release by Cytokine Type TNF-a | 8.3 ng/L | 9.7 ng/L | 9.7 ng/L | 24.2 ng/L | 8.3 ng/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 15 Participants | 6 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 2 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 8 Participants | 4 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 0 / 3 | 1 / 3 | 1 / 6 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 1 / 3 | 3 / 6 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a study participant administered a study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a Possible or Related relationship to study treatment, as assessed by the Investigator. The number of participants who discontinued study treatment due to a treatment-related AE is presented.
Time frame: Up to last injection (Up to approximately 102 days)
Population: The safety population consisted of all participants who received ≥1 injection of MK-4621.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: MK-4621 0.2 mg | Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE) | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE) | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE) | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Discontinued Study Treatment Due to a Treatment-related Adverse Event (AE) | 0 Participants |
Primary
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria
DLTs were assessed during the first treatment cycle (28 days) & were defined as any drug-related toxicity that occurred during the 28-day DLT period and included: * Non-hematologic toxicity grade ≥3 (except diarrhea, nausea, and vomiting unless lasting \>3 days despite optimal supportive care); * Confirmed (with a second measurement after 24 hours) non-hematologic appropriately graded laboratory findings of Grade ≥3 that were ≤ Grade 1 at baseline; * Hematologic toxicity: * Grade 4 neutropenia ≥5 days, or Grade 3 neutropenia with fever (fever is \>38.4ºC) * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia lasting \>7 days or with bleeding; and * Any other toxicity assessed as related to MK-4621, and which, in the opinion of the Investigator and the Sponsor physician constituted a DLT. The number of participants who experienced a DLT is presented by NCI CTCAE version 4.03 severity grade.
Time frame: Cycle 1 (Up to approximately 28 days); Each cycle was 28 days.
Population: The DLT evaluable population consisted of participants who completed Cycle 1 (Day 28) or withdrew early for experiencing a DLT.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 0 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 0 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 0 Participants |
Primary
Number of Participants Who Experienced a Serious Adverse Event (SAE)
A SAE was defined as any AE, regardless of dose, causality or expectedness, that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolonged existing inpatient hospitalization; * Resulted in persistent or significant incapacity or disability; * Was a congenital anomaly or birth defect; or * Was any other medically important event.
Time frame: Up to 90 days post last injection (Up to approximately 192 days)
Population: The safety population consisted of all participants who received ≥1 injection of MK-4621.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 2 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 2 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 1 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 3 Participants |
Primary
Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria
An AE was defined as any untoward medical occurrence in a study participant administered study treatment which did not necessarily have a causal relationship with this treatment. Treatment-related was defined as having a Possible or Related relationship to study treatment, as assessed by the Investigator. Severity of AE referred to the extent to which an AE affected the participants daily activities as assessed by the Investigator and was based on NCI CTCAE grades: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe or medically significant but not immediately life-threatening); Grade 4 (Life-threatening consequences); or Grade 5 (Death related to AE). The number of participants who experienced at least one treatment-related AE or laboratory abnormality are presented by severity.
Time frame: Up to 90 days post last injection (Up to approximately 192 days)
Population: The safety population consisted of all participants who received ≥1 injection of MK-4621.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 1 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 0 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 1 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.2 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 2 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 1 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 0 Participants |
| Group A: MK-4621 0.4 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 1 Participants |
| Group A: MK-4621 0.6 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 2 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 2 | 2 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 3 | 1 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 5 | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 4 | 0 Participants |
| Group A: MK-4621 0.8 mg | Number of Participants Who Experienced a Treatment-related Adverse Event (AE) or Laboratory Abnormality by Severity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Criteria | Grade 1 | 3 Participants |
Secondary
Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
ORR was defined as the percentage of participants who had a Complete Response (CR) or a Partial Response. Per irRECIST, CR (irCR) was defined as the complete disappearance of all measurable and non-measurable lesions. Lymph nodes must also have decreased to \<0 mm in short axis. And, per irRECIST, Partial Response (irPR) was defined as a decrease of ≥30% in total measured tumor burden (TMTB) relative to baseline. For this study, irRECIST was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced an irCR or irPR based on irRECIST is presented.
Time frame: Up to 60 days post last injection (Up to approximately 162 days)
Population: The efficacy population consisted of all allocated participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: MK-4621 0.2 mg | Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 0 Percentage of Participants |
| Group A: MK-4621 0.4 mg | Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 0 Percentage of Participants |
| Group A: MK-4621 0.6 mg | Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 0 Percentage of Participants |
| Group A: MK-4621 0.8 mg | Objective Response Rate as Evaluated Radiologically Using Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | 0 Percentage of Participants |
Other Pre-specified
Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1
Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 AUC0-t on Day 1, which was defined as the AUC from the start time of dosing to the time of the last observed concentration above the limit of quantitation (LOQ).
Time frame: Cycle 1 Day 1: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 2 days); Each cycle was 28 days.
Population: The pharmacokinetic evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment pharmacokinetic data for AUC0-t on Cycle 1 Day 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1 | 0.00 h*ng/mL | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1 | 0.174 h*ng/mL | Standard Deviation 0.157 |
| Group A: MK-4621 0.6 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1 | 0.0360 h*ng/mL | Standard Deviation 0.0623 |
| Group A: MK-4621 0.8 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 1 | 1.87 h*ng/mL | Standard Deviation 4.55 |
Other Pre-specified
Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25
Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 AUC0-t on Day 25, which was defined as the AUC from the start time of dosing to the time of the last observed concentration above the limit of quantitation (LOQ).
Time frame: Cycle 1 Day 25: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 26 days); Each cycle was 28 days.
Population: The pharmacokinetic evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment pharmacokinetic data for AUC0-t on Cycle 1 Day 25.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25 | 0.00 h*ng/mL | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25 | 1.07 h*ng/mL | Standard Deviation 0.767 |
| Group A: MK-4621 0.6 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25 | 0.099 h*ng/mL | Standard Deviation 0.172 |
| Group A: MK-4621 0.8 mg | Area Under the Concentration-Time Curve From Start of Dosing to Last Observed Concentration Above Limit of Quantitation (AUC0-t) of MK-4621: Day 25 | 0.156 h*ng/mL | Standard Deviation 0.35 |
Other Pre-specified
Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1
Sequential participant tumor biopsies were assessed via immunohistochemistry for the presence of tumor infiltrating CD3 T cell co-receptor-marked cells and Ki-67 nuclear protein-marked cells in tumor biopsies. CD3 is a marker of T cells and KI-67 is a cell marker of proliferation and activation. The percentage of positive CD3-marked cells and double-positive CD3 and Ki-67 nuclear protein-marked cells in tumor biopsies predose on Day 1 are presented.
Time frame: Day 1 prior to injection (Up to 1 day)
Population: The immune infiltration evaluable population consisted of all participants who received ≥1 dose of MK-4621 and had pre- and post-treatment immune infiltration data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | CD3 Cells | 8.81 Percentage Positive Cells |
| Group A: MK-4621 0.2 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | Ki-67 Positive CD3 Cells | 25.44 Percentage Positive Cells |
| Group A: MK-4621 0.4 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | Ki-67 Positive CD3 Cells | 25.19 Percentage Positive Cells |
| Group A: MK-4621 0.4 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | CD3 Cells | 17.58 Percentage Positive Cells |
| Group A: MK-4621 0.6 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | CD3 Cells | 34.64 Percentage Positive Cells |
| Group A: MK-4621 0.6 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | Ki-67 Positive CD3 Cells | 39.23 Percentage Positive Cells |
| Group A: MK-4621 0.8 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | CD3 Cells | 17.34 Percentage Positive Cells |
| Group A: MK-4621 0.8 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 1 | Ki-67 Positive CD3 Cells | 32.19 Percentage Positive Cells |
Other Pre-specified
Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25
Sequential participant tumor biopsies were assessed via immunohistochemistry for the presence of tumor infiltrating CD3 T cell co-receptor-marked cells and Ki-67 nuclear protein-marked cells in tumor biopsies. CD3 is a marker of T cells and KI-67 is a cell marker of proliferation and activation. The percentage of positive CD3-marked cells and double-positive CD3 and Ki-67 nuclear protein-marked cells in tumor biopsies postdose on Day 25 are presented.
Time frame: Day 25 post injection (Up to 25 days)
Population: The immune infiltration evaluable population consisted of all participants who received ≥1 dose of MK-4621 and had pre- and post-treatment immune infiltration data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | CD3 Cells | 12.72 Percentage Positive Cells |
| Group A: MK-4621 0.2 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | Ki-67 Positive CD3 Cells | 16.96 Percentage Positive Cells |
| Group A: MK-4621 0.4 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | Ki-67 Positive CD3 Cells | 36.39 Percentage Positive Cells |
| Group A: MK-4621 0.4 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | CD3 Cells | 8.43 Percentage Positive Cells |
| Group A: MK-4621 0.6 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | CD3 Cells | 11.77 Percentage Positive Cells |
| Group A: MK-4621 0.6 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | Ki-67 Positive CD3 Cells | 17.93 Percentage Positive Cells |
| Group A: MK-4621 0.8 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | CD3 Cells | 32.19 Percentage Positive Cells |
| Group A: MK-4621 0.8 mg | Immune Infiltration of Injected Tumors by CD3 T Cell Receptor and Ki-67 Nuclear Protein: Day 25 | Ki-67 Positive CD3 Cells | 12.16 Percentage Positive Cells |
Other Pre-specified
Maximum Plasma Concentration (Cmax) of MK-4621: Day 1
Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 Cmax on Day 1.
Time frame: Cycle 1 Day 1: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 2 days); Each cycle was 28 days.
Population: The pharmacokinetic evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment pharmacokinetic data for Cmax on Cycle 1 Day 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 1 | 0.00 ng/mL | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 1 | 4.18 ng/mL | Standard Deviation 3.76 |
| Group A: MK-4621 0.6 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 1 | 0.863 ng/mL | Standard Deviation 1.5 |
| Group A: MK-4621 0.8 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 1 | 9.24 ng/mL | Standard Deviation 21.9 |
Other Pre-specified
Maximum Plasma Concentration (Cmax) of MK-4621: Day 25
Blood samples were collected at various time points during Cycle 1 for the determination of MK-4621 Cmax on Day 25.
Time frame: Cycle 1 Day 25: Predose, 5 and 30 minutes, 2, 4, 6 and 24 hours post dose (Up to 26 days); Each cycle was 28 days.
Population: The pharmacokinetic evaluable population consisted of all participants who received ≥1 injection of MK-4621 and had pre- and post-treatment pharmacokinetic data for Cmax on Cycle 1 Day 25.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: MK-4621 0.2 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 25 | 0.00 ng/mL | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 25 | 7.43 ng/mL | Standard Deviation 2.44 |
| Group A: MK-4621 0.6 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 25 | 1.703 ng/mL | Standard Deviation 2.95 |
| Group A: MK-4621 0.8 mg | Maximum Plasma Concentration (Cmax) of MK-4621: Day 25 | 3.75 ng/mL | Standard Deviation 8.39 |
Other Pre-specified
Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection)
Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma.
Time frame: Baseline and Cycle 1 Day 1 (24 hours post injection) (Up to 2 days); Each cycle was 28 days.
Population: The cytokine evaluable population consisted of all participants who received ≥1 dose of MK-4621 and had baseline and post treatment cytokine data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | IL-6 | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | IL-6 | 1.27 Fold change | Standard Deviation 0.46 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | IL-6 | 1.14 Fold change | Standard Deviation 0.3 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | TNF-a | 1.48 Fold change | Standard Deviation 1.44 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | IL-6 | 1.68 Fold change | Standard Deviation 0.97 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (24 Hours Post Injection) | TNF-a | 0.89 Fold change | Standard Deviation 0.28 |
Other Pre-specified
Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection)
Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma.
Time frame: Baseline and Cycle 1 Day 1 (6 hours post injection) (Up to 1 day); Each cycle was 28 days.
Population: The cytokine evaluable population consisted of all participants who received ≥1 dose of MK-4621 and had baseline and post treatment cytokine data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | IL-6 | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | IL-6 | 1.95 Fold change | Standard Deviation 1.64 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | IL-6 | 2.71 Fold change | Standard Deviation 2.34 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0.6 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | IL-6 | 2.52 Fold change | Standard Deviation 3.14 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 1 (6 Hours Post Injection) | TNF-a | 0.89 Fold change | Standard Deviation 0.28 |
Other Pre-specified
Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection)
Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma.
Time frame: Baseline and Cycle 1 Day 25 (24 hours post injection) (Up to 26 days); Each cycle was 28 days.
Population: The cytokine evaluable population consisted of all participants who received ≥1 dose of MK-4621 and had baseline and post treatment cytokine data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | IL-6 | 1.52 Fold change | Standard Deviation 0.9 |
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | IL-6 | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | IL-6 | 0.99 Fold change | Standard Deviation 0.1 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | TNF-a | 1.02 Fold change | Standard Deviation 0.63 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | IL-6 | 0.89 Fold change | Standard Deviation 0.19 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (24 Hours Post Injection) | TNF-a | 0.88 Fold change | Standard Deviation 0.32 |
Other Pre-specified
Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection)
Blood samples were collected at various time points for the analysis of mean fold change from baseline in cytokine release for selected cytokines (Interleukin-6 \[IL-6\] and tumor necrosis factor-alpha \[TNF-a\]) in plasma.
Time frame: Baseline and Cycle 1 Day 25 (6 hours post injection) (Up to 25 days); Each cycle was 28 days.
Population: The cytokine evaluable population consisted of all participants who received ≥1 dose of MK-4621 and had baseline and post treatment cytokine data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | IL-6 | 0.95 Fold change | Standard Deviation 0.08 |
| Group A: MK-4621 0.2 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | TNF-a | 1 Fold change | Standard Deviation 0 |
| Group A: MK-4621 0.4 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | IL-6 | 2 Fold change | Standard Deviation 1.11 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | TNF-a | 0.77 Fold change | Standard Deviation 0.21 |
| Group A: MK-4621 0.6 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | IL-6 | 1.02 Fold change | Standard Deviation 0.31 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | TNF-a | 0.77 Fold change | Standard Deviation 0.29 |
| Group A: MK-4621 0.8 mg | Mean Fold Change From Baseline in Plasma Cytokine Release by Cytokine Type: Day 25 (6 Hours Post Injection) | IL-6 | 1.5 Fold change | Standard Deviation 0.61 |