Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155/KEYNOTE-155)
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) used in combination with dinaciclib (MK-7965) in the treatment of relapsed or refractory chronic lymphocytic leukemia (rrCLL), multiple myeloma (rrMM), or diffuse large B-cell lymphoma (rrDLBCL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: rrCLL Cohort Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
Biological: pembrolizumab
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35. Each cycle is 21 days.
Other Names:
Drug: dinaciclib
dinaciclib 7 mg/m^2 administered as an IV infusion on Day 1 of infusion Cycle 1, dinaciclib 10 mg/m^2 administered as an IV infusion on Day 8 of infusion Cycle 1, dinaciclib 14 mg/m^2 administered as an IV infusion on Days 1 and 8 of infusion Cycles 2-35. Each cycle is 21 days.
Other Names:
|
| Experimental: rrMM Cohort Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
Biological: pembrolizumab
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35. Each cycle is 21 days.
Other Names:
Drug: dinaciclib
dinaciclib 7 mg/m^2 administered as an IV infusion on Day 1 of infusion Cycle 1, dinaciclib 10 mg/m^2 administered as an IV infusion on Day 8 of infusion Cycle 1, dinaciclib 14 mg/m^2 administered as an IV infusion on Days 1 and 8 of infusion Cycles 2-35. Each cycle is 21 days.
Other Names:
|
| Experimental: rrDLBCL Cohort Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
Biological: pembrolizumab
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35. Each cycle is 21 days.
Other Names:
Drug: dinaciclib
dinaciclib 7 mg/m^2 administered as an IV infusion on Day 1 of infusion Cycle 1, dinaciclib 10 mg/m^2 administered as an IV infusion on Day 8 of infusion Cycle 1, dinaciclib 14 mg/m^2 administered as an IV infusion on Days 1 and 8 of infusion Cycles 2-35. Each cycle is 21 days.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicity (DLT) [Up to 42 days]
DLTs consisted of the following if observed during treatment Cycles 1 or 2 and assessed by investigator to be possibly, probably, or definitely related to pembrolizumab or dinaciclib: grade 4 non-laboratory nonhematologic toxicity; grade 4 hematologic toxicity lasting >7 days (except thrombocytopenia); grade 4 thrombocytopenia of any duration; grade 3 thrombocytopenia if associated with bleeding; any grade 3 non-laboratory nonhematologic toxicity, except grade 3 nausea, vomiting, or diarrhea, which was not considered a DLT unless lasting more than 3 days despite optimal supportive care; Grade 3 or Grade 4 nonhematologic laboratory abnormality that required medical intervention, led to hospitalization, or persisted for >1 week; grade 3 or 4 febrile neutropenia; any drug-related AE that caused participant to discontinue treatment during Cycles 1 or 2; grade 5 toxicity; treatment-related toxicity that caused a >2-week delay in initiation of treatment Cycle 2 or 3. Each cycle was 21 days.
- Number of Participants Who Experienced an Adverse Event [Up to approximately 582 days]
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was presented.
- Number of Participants Who Discontinued Treatment Due to an Adverse Event [Up to 492 days]
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.
Secondary Outcome Measures
- Objective Response Rate (ORR) [Up to approximately 26 months]
ORR is defined in participants with CLL as the percentage of participants who have a confirmed Complete Response (CR) or Partial Response (PR) per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008) as assessed by the investigator; in participants with DLBCL as the above definition but per the Revised Response Criteria for Malignant Lymphoma (2007) as assessed by the investigator; and in participants with MM as the percentage of participants who have a confirmed Stringent Complete Response (sCR), CR, PR, or Very Good Partial Remission (VGPR) per the International Uniform Response Criteria for Multiple Myeloma (2006) as assessed by the investigator.
- Duration of Response (DOR) [Up to approximately 26 months]
DOR is the time from initial response to Progressive Disease (PD) or death, whichever occurred first. A response was: in participants with CLL, a confirmed Complete Response (CR) or Partial Response (PR) per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008); in participants with DLBCL, as above but per the Revised Response Criteria for Malignant Lymphoma (2007); and in participants with MM, a confirmed Stringent Complete Response (sCR), CR, PR, or Very Good Partial Remission (VGPR) per the International Uniform Response Criteria for Multiple Myeloma (2006). The above guidelines also define PD by disease. Assessments were by investigator. Data were censored at last disease assessment documenting absence of PD for participants who: had no PD and were still on the trial; received antitumor treatment other than that of the trial; or were removed from trial prior to PD. DOR was analyzed using the product-limit (Kaplan-Meier) method for censored data.
- Progression-Free Survival (PFS) [Up to approximately 26 months]
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD evaluations were done based on the cancer-specific criteria of: the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008) in participants with CLL; the Revised Response Criteria for Malignant Lymphoma (2007) in participants with DLBCL; and the International Uniform Response Criteria for Multiple Myeloma (2006) in participants with MM. Assessments were by investigator. PFS data were censored for participants with no PD or death at their last disease assessment, or at their last disease assessment prior to starting new anticancer treatment for those who did so. PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
- Overall Survival (OS) [Up to approximately 44 months]
OS was defined as the time from first dose of study treatment to death due to any cause. Data were censored at the date of a participant's last follow-up. OS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Females must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start)
-
Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
-
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
-
Cardiac function suitable for protocol-required hydration as determined by the investigator and/or cardiologist
-
Must be able to provide biopsy specimens obtained ≤3 months for biomarker analysis. If bone marrow biopsy was performed 3 months before screening but subject had anti-cancer treatment after biopsy, the bone marrow biopsy and aspiration should be repeated
Relapsed or refractory chronic lymphocytic leukemia (rrCLL) participants:
-
Must have a confirmed diagnosis of CLL defined by 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
-
Must have received one prior therapy for CLL
-
Must meet one or more of the consensus criteria for initiating treatment
Relapsed or refractory multiple myelolma (rrMM) participants:
-
Must have a confirmed diagnosis of active MM
-
Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and failed last line of treatment (disease progression ≤60 days of completion of last therapy)
-
Must have failed prior anti-myeloma treatments that have included an immunomodulatory drug (IMiD) (pomalidomide, lenalidomide, or thalidomide) AND proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination
Diffuse large B-cell lymphoma (rrDLBCL) participants:
-
Must have a confirmed diagnosis of DLBCL and have progressed following ≥2 lines of previous therapy, after autologous stem cell transplant, or not a candidate for autologous stem cell transplant
-
Must have measurable disease (≥1 lesion that is >15 mm in the longest diameter or by
10 mm in the short axis)
Exclusion Criteria:
-
Has been treated with a cytochrome P450 3A4 (CYP3A4) strong inhibitor or inducer within 7 days of enrollment
-
Has been treated with anti-cancer therapy or thoracic radiation therapy within 14 days
-
Has known clinically active central nervous system (CNS) involvement
-
Has a known history of immunosuppression or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days
-
Has had prior anti-cancer monoclonal antibody within 4 weeks of Study Day 1 or who has not recovered from adverse events due to agents administered >4 weeks earlier
-
Has undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years
-
Has a known additional malignancy that is progressing or requires active treatment
-
Has active autoimmune disease that has required systemic treatment in past 2 years
-
Has an active infection requiring intravenous systemic therapy
-
Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death ligand (PD-L) 1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) or chimeric antigen receptor (CAR)-T cell therapy or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
-
Has been previously treated with a cyclin-dependent kinase (CDK) inhibitor
-
Has a known history of Human Immunodeficiency Virus (HIV) infection
-
Has a known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus RNA [qualitative] is detected)
-
Has received a live vaccine within 30 days prior to the first dose of trial treatment
-
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
-
Has known current symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
Relapsed or refractory chronic lymphocytic leukemia (rrCLL) participants:
- Has Richter's Transformation
Relapsed or refractory multiple myelolma (rrMM) participants:
-
Participants with non-secretory or oligo-secretory myeloma, plasma cell leukemia or Waldenström's macroglobulinemia
-
History of primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Diffuse large B-cell lymphoma (rrDLBCL) participants:
-
Participants with primary mediastinal B-cell lymphoma (PMBCL)
-
Has Richter's Transformation
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 3475-155
- MK-3475-155
- KEYNOTE-155
Study Results
Participant Flow
| Recruitment Details | The rrMM Cohort was closed to enrollment on 07-AUG-2017 due to lack of efficacy. The rrCLL Cohort was closed to enrollment on 30-APR-2019 due to lack of efficacy. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Period Title: Overall Study | |||
| STARTED | 18 | 17 | 40 |
| Treated | 17 | 17 | 38 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 18 | 17 | 40 |
Baseline Characteristics
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Total of all reporting groups |
| Overall Participants | 17 | 17 | 38 | 72 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
68.1
(10.9)
|
60.8
(9.5)
|
64.1
(11.1)
|
64.3
(10.9)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
17.6%
|
11
64.7%
|
15
39.5%
|
29
40.3%
|
| Male |
14
82.4%
|
6
35.3%
|
23
60.5%
|
43
59.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
1
5.9%
|
4
10.5%
|
5
6.9%
|
| Not Hispanic or Latino |
17
100%
|
16
94.1%
|
34
89.5%
|
67
93.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
4
10.5%
|
4
5.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
5.9%
|
3
17.6%
|
2
5.3%
|
6
8.3%
|
| White |
16
94.1%
|
14
82.4%
|
32
84.2%
|
62
86.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Participants With Dose Limiting Toxicity (DLT) |
|---|---|
| Description | DLTs consisted of the following if observed during treatment Cycles 1 or 2 and assessed by investigator to be possibly, probably, or definitely related to pembrolizumab or dinaciclib: grade 4 non-laboratory nonhematologic toxicity; grade 4 hematologic toxicity lasting >7 days (except thrombocytopenia); grade 4 thrombocytopenia of any duration; grade 3 thrombocytopenia if associated with bleeding; any grade 3 non-laboratory nonhematologic toxicity, except grade 3 nausea, vomiting, or diarrhea, which was not considered a DLT unless lasting more than 3 days despite optimal supportive care; Grade 3 or Grade 4 nonhematologic laboratory abnormality that required medical intervention, led to hospitalization, or persisted for >1 week; grade 3 or 4 febrile neutropenia; any drug-related AE that caused participant to discontinue treatment during Cycles 1 or 2; grade 5 toxicity; treatment-related toxicity that caused a >2-week delay in initiation of treatment Cycle 2 or 3. Each cycle was 21 days. |
| Time Frame | Up to 42 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received ≥1 dose of study medication, and who did not discontinue within the first two 21-day cycles of treatment or who experienced a DLT prior to completing the first two cycles of treatment. |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Measure Participants | 3 | 3 | 6 |
| Count of Participants [Participants] |
1
5.9%
|
1
5.9%
|
1
2.6%
|
| Title | Number of Participants Who Experienced an Adverse Event |
|---|---|
| Description | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was presented. |
| Time Frame | Up to approximately 582 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received ≥1 dose of study treatment. |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Measure Participants | 17 | 17 | 38 |
| Count of Participants [Participants] |
17
100%
|
16
94.1%
|
37
97.4%
|
| Title | Number of Participants Who Discontinued Treatment Due to an Adverse Event |
|---|---|
| Description | An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented. |
| Time Frame | Up to 492 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received ≥1 dose of study treatment. |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Measure Participants | 17 | 17 | 38 |
| Count of Participants [Participants] |
4
23.5%
|
2
11.8%
|
0
0%
|
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | ORR is defined in participants with CLL as the percentage of participants who have a confirmed Complete Response (CR) or Partial Response (PR) per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008) as assessed by the investigator; in participants with DLBCL as the above definition but per the Revised Response Criteria for Malignant Lymphoma (2007) as assessed by the investigator; and in participants with MM as the percentage of participants who have a confirmed Stringent Complete Response (sCR), CR, PR, or Very Good Partial Remission (VGPR) per the International Uniform Response Criteria for Multiple Myeloma (2006) as assessed by the investigator. |
| Time Frame | Up to approximately 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received ≥1 dose of study treatment. |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Measure Participants | 17 | 17 | 38 |
| Number (95% Confidence Interval) [Percentage of Participants] |
29.4
172.9%
|
0.0
0%
|
21.1
55.5%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR is the time from initial response to Progressive Disease (PD) or death, whichever occurred first. A response was: in participants with CLL, a confirmed Complete Response (CR) or Partial Response (PR) per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008); in participants with DLBCL, as above but per the Revised Response Criteria for Malignant Lymphoma (2007); and in participants with MM, a confirmed Stringent Complete Response (sCR), CR, PR, or Very Good Partial Remission (VGPR) per the International Uniform Response Criteria for Multiple Myeloma (2006). The above guidelines also define PD by disease. Assessments were by investigator. Data were censored at last disease assessment documenting absence of PD for participants who: had no PD and were still on the trial; received antitumor treatment other than that of the trial; or were removed from trial prior to PD. DOR was analyzed using the product-limit (Kaplan-Meier) method for censored data. |
| Time Frame | Up to approximately 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received ≥1 dose of study treatment and experienced a response to study treatment. |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Measure Participants | 5 | 0 | 8 |
| Median (Full Range) [Months] |
NA
|
4.9
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD evaluations were done based on the cancer-specific criteria of: the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008) in participants with CLL; the Revised Response Criteria for Malignant Lymphoma (2007) in participants with DLBCL; and the International Uniform Response Criteria for Multiple Myeloma (2006) in participants with MM. Assessments were by investigator. PFS data were censored for participants with no PD or death at their last disease assessment, or at their last disease assessment prior to starting new anticancer treatment for those who did so. PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data. |
| Time Frame | Up to approximately 26 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received ≥1 dose of study treatment. |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Measure Participants | 17 | 17 | 38 |
| Median (95% Confidence Interval) [Months] |
5.2
|
1.6
|
2.1
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from first dose of study treatment to death due to any cause. Data were censored at the date of a participant's last follow-up. OS was analyzed using the product-limit (Kaplan-Meier) method for censored data. |
| Time Frame | Up to approximately 44 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received ≥1 dose of study treatment. |
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort |
|---|---|---|---|
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. |
| Measure Participants | 17 | 17 | 38 |
| Median (95% Confidence Interval) [Months] |
21.7
|
10.5
|
7.9
|
Adverse Events
| Time Frame | Up to approximately 522 days for non-serious adverse events. Up to approximately 582 days for serious adverse events. Up to approximately 610 days for all-cause mortality. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | MedDRA preferred terms "neoplasm progression", "malignant neoplasm progression" and "disease progression" not related to the drug are excluded. | |||||
| Arm/Group Title | rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort | |||
| Arm/Group Description | Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8. Each cycle is 21 days. | |||
All Cause Mortality |
||||||
| rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/17 (52.9%) | 16/17 (94.1%) | 32/38 (84.2%) | |||
Serious Adverse Events |
||||||
| rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/17 (76.5%) | 6/17 (35.3%) | 17/38 (44.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Febrile neutropenia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Pancytopenia | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Thrombocytopenia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Coronary artery disease | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Vertigo positional | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Duodenal ulcer haemorrhage | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| General disorders | ||||||
| Chills | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Death | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Drug withdrawal syndrome | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Pyrexia | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Systemic inflammatory response syndrome | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Bile duct obstruction | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Immune system disorders | ||||||
| Cytokine release syndrome | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Infections and infestations | ||||||
| Bronchitis viral | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Disseminated tuberculosis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Osteomyelitis | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Perirectal abscess | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Pneumonia | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Pulmonary sepsis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Respiratory syncytial virus infection | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Sepsis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Vascular access complication | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Wound | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Investigations | ||||||
| Blood creatinine increased | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Dehydration | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Hypercalcaemia | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Hyperglycaemia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Hyperkalaemia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Tumour lysis syndrome | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| Flank pain | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Muscular weakness | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Bladder transitional cell carcinoma | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Squamous cell carcinoma of skin | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Nervous system disorders | ||||||
| Loss of consciousness | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Psychiatric disorders | ||||||
| Mental status changes | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Suicidal ideation | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 1/17 (5.9%) | 1 | 3/17 (17.6%) | 4 | 1/38 (2.6%) | 1 |
| Renal failure | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Urinary retention | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Pleural effusion | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 2/38 (5.3%) | 2 |
| Pneumonitis | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Vascular disorders | ||||||
| Deep vein thrombosis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Hypertension | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Hypotension | 0/17 (0%) | 0 | 2/17 (11.8%) | 2 | 0/38 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| rrCLL Cohort | rrMM Cohort | rrDLBCL Cohort | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/17 (100%) | 16/17 (94.1%) | 37/38 (97.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 7/17 (41.2%) | 8 | 6/17 (35.3%) | 6 | 6/38 (15.8%) | 9 |
| Febrile neutropenia | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Haemorrhagic diathesis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Increased tendency to bruise | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Leukocytosis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Neutropenia | 5/17 (29.4%) | 13 | 2/17 (11.8%) | 2 | 4/38 (10.5%) | 8 |
| Thrombocytopenia | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 2/38 (5.3%) | 3 |
| Cardiac disorders | ||||||
| Angina pectoris | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Atrial fibrillation | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 2 |
| Palpitations | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 1/38 (2.6%) | 2 |
| Sinus tachycardia | 1/17 (5.9%) | 3 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Ear and labyrinth disorders | ||||||
| Deafness | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Ear pain | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Vertigo | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Endocrine disorders | ||||||
| Hypothyroidism | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Eye disorders | ||||||
| Vision blurred | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Abdominal distension | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Abdominal pain | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 6/38 (15.8%) | 7 |
| Abdominal pain lower | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Constipation | 3/17 (17.6%) | 3 | 3/17 (17.6%) | 3 | 14/38 (36.8%) | 19 |
| Diarrhoea | 3/17 (17.6%) | 3 | 3/17 (17.6%) | 3 | 10/38 (26.3%) | 17 |
| Dry mouth | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Gastritis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Gastrooesophageal reflux disease | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Mouth ulceration | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Nausea | 7/17 (41.2%) | 10 | 4/17 (23.5%) | 4 | 15/38 (39.5%) | 18 |
| Post-tussive vomiting | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Retching | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Stomatitis | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Toothache | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Vomiting | 2/17 (11.8%) | 2 | 2/17 (11.8%) | 3 | 4/38 (10.5%) | 5 |
| General disorders | ||||||
| Asthenia | 0/17 (0%) | 0 | 2/17 (11.8%) | 2 | 1/38 (2.6%) | 1 |
| Axillary pain | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Catheter site erythema | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 2 |
| Catheter site pain | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Chest pain | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Chills | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Early satiety | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Fatigue | 11/17 (64.7%) | 12 | 6/17 (35.3%) | 7 | 12/38 (31.6%) | 15 |
| Gait disturbance | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| General physical health deterioration | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Influenza like illness | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Infusion site irritation | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Infusion site reaction | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Mucosal haemorrhage | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Oedema | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Oedema peripheral | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 8/38 (21.1%) | 10 |
| Pain | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 2/38 (5.3%) | 2 |
| Peripheral swelling | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Pyrexia | 2/17 (11.8%) | 2 | 1/17 (5.9%) | 1 | 7/38 (18.4%) | 11 |
| Swelling face | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Infections and infestations | ||||||
| Cellulitis | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Clostridium difficile colitis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Gingivitis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Incision site cellulitis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Nasopharyngitis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Onychomycosis | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Oral candidiasis | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Oral herpes | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Pneumonia | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Postoperative wound infection | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Sinusitis | 1/17 (5.9%) | 3 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Tooth abscess | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Upper respiratory tract infection | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 8/38 (21.1%) | 14 |
| Viral upper respiratory tract infection | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 1/17 (5.9%) | 9 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Contusion | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Eye contusion | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Fall | 2/17 (11.8%) | 3 | 1/17 (5.9%) | 1 | 2/38 (5.3%) | 2 |
| Hand fracture | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Infusion related reaction | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Rib fracture | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Skin laceration | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Thermal burn | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Aspartate aminotransferase increased | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 5/38 (13.2%) | 5 |
| Blood alkaline phosphatase increased | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Blood creatinine increased | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 3/38 (7.9%) | 3 |
| Blood magnesium decreased | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Blood phosphorus decreased | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Blood potassium decreased | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Body height decreased | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Haemoglobin decreased | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Lymphocyte count decreased | 1/17 (5.9%) | 2 | 2/17 (11.8%) | 2 | 8/38 (21.1%) | 11 |
| Lymphocyte count increased | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Neutrophil count decreased | 4/17 (23.5%) | 7 | 0/17 (0%) | 0 | 7/38 (18.4%) | 9 |
| Platelet count decreased | 4/17 (23.5%) | 4 | 4/17 (23.5%) | 4 | 8/38 (21.1%) | 8 |
| Weight decreased | 3/17 (17.6%) | 3 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Weight increased | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| White blood cell count decreased | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 6/38 (15.8%) | 8 |
| Metabolism and nutrition disorders | ||||||
| Alkalosis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Decreased appetite | 2/17 (11.8%) | 2 | 1/17 (5.9%) | 1 | 7/38 (18.4%) | 8 |
| Fluid retention | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Gout | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Hypercalcaemia | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 2 |
| Hyperglycaemia | 4/17 (23.5%) | 4 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Hyperkalaemia | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Hyperuricaemia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Hypoalbuminaemia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Hypocalcaemia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Hypoglycaemia | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Hypokalaemia | 1/17 (5.9%) | 1 | 3/17 (17.6%) | 5 | 5/38 (13.2%) | 7 |
| Hypomagnesaemia | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Hyponatraemia | 1/17 (5.9%) | 1 | 3/17 (17.6%) | 3 | 4/38 (10.5%) | 5 |
| Hypophosphataemia | 2/17 (11.8%) | 3 | 0/17 (0%) | 0 | 6/38 (15.8%) | 11 |
| Tumour lysis syndrome | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Vitamin D deficiency | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/17 (0%) | 0 | 2/17 (11.8%) | 2 | 4/38 (10.5%) | 4 |
| Back pain | 1/17 (5.9%) | 1 | 2/17 (11.8%) | 2 | 5/38 (13.2%) | 5 |
| Bone pain | 0/17 (0%) | 0 | 2/17 (11.8%) | 2 | 0/38 (0%) | 0 |
| Exostosis | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Flank pain | 2/17 (11.8%) | 2 | 1/17 (5.9%) | 1 | 4/38 (10.5%) | 4 |
| Groin pain | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Joint swelling | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Muscle spasms | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 3/38 (7.9%) | 3 |
| Musculoskeletal chest pain | 1/17 (5.9%) | 1 | 2/17 (11.8%) | 2 | 0/38 (0%) | 0 |
| Musculoskeletal pain | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Pain in extremity | 3/17 (17.6%) | 3 | 3/17 (17.6%) | 3 | 3/38 (7.9%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Acrochordon | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Squamous cell carcinoma | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Nervous system disorders | ||||||
| Balance disorder | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Dizziness | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 5/38 (13.2%) | 6 |
| Dizziness postural | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Dysgeusia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Headache | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 8/38 (21.1%) | 8 |
| Hypoaesthesia | 1/17 (5.9%) | 1 | 2/17 (11.8%) | 2 | 0/38 (0%) | 0 |
| Hypogeusia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Hyposmia | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Lethargy | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 2/38 (5.3%) | 2 |
| Paraesthesia | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Presyncope | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Psychiatric disorders | ||||||
| Anxiety | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 2/38 (5.3%) | 2 |
| Confusional state | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Depression | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Insomnia | 2/17 (11.8%) | 2 | 1/17 (5.9%) | 1 | 3/38 (7.9%) | 3 |
| Mood altered | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Haematuria | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Renal impairment | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Urinary incontinence | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Dyspareunia | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Bronchiectasis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Cough | 4/17 (23.5%) | 4 | 7/17 (41.2%) | 7 | 4/38 (10.5%) | 5 |
| Dyspnoea | 1/17 (5.9%) | 1 | 2/17 (11.8%) | 2 | 4/38 (10.5%) | 4 |
| Dyspnoea exertional | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 3/38 (7.9%) | 3 |
| Epistaxis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Hiccups | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Hypoxia | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Nasal congestion | 3/17 (17.6%) | 3 | 2/17 (11.8%) | 2 | 2/38 (5.3%) | 2 |
| Oropharyngeal pain | 2/17 (11.8%) | 2 | 2/17 (11.8%) | 2 | 2/38 (5.3%) | 2 |
| Pleural effusion | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Productive cough | 1/17 (5.9%) | 2 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Rhinorrhoea | 1/17 (5.9%) | 1 | 1/17 (5.9%) | 1 | 0/38 (0%) | 0 |
| Sinus congestion | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Upper-airway cough syndrome | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Actinic keratosis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Dermatitis acneiform | 1/17 (5.9%) | 5 | 0/17 (0%) | 0 | 1/38 (2.6%) | 3 |
| Dry skin | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 3 |
| Erythema | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Hyperhidrosis | 1/17 (5.9%) | 2 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Night sweats | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Papule | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/38 (0%) | 0 |
| Pruritus | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 3/38 (7.9%) | 5 |
| Rash | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 5/38 (13.2%) | 5 |
| Rash maculo-papular | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 1/38 (2.6%) | 1 |
| Skin lesion | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 2/38 (5.3%) | 2 |
| Vascular disorders | ||||||
| Hypertension | 1/17 (5.9%) | 2 | 1/17 (5.9%) | 1 | 1/38 (2.6%) | 1 |
| Hypotension | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 4/38 (10.5%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
- 3475-155
- MK-3475-155
- KEYNOTE-155