Renal Cell Cancer
Conditions
Brief summary
This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic infiltration in at least 30% of participants with RCC.
Interventions
DRUGPembrolizumab Pre-Resection
200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles
PROCEDURESurgical Resection
Standard of care surgical resection of RCC tumor
DRUGPembrolizumab Post-Resection
200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (\>= T1b), not previously treated, and be a candidate for operative tumor resection * Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale * Demonstrate adequate organ function * Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment * Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw.
Exclusion criteria
* Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy * Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy * Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC * Has a known additional (other than RCC) malignancy that is progressing or requires active treatment * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy * Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis. * Has an active infection requiring systematic therapy * Is receiving anticoagulant therapy, with the exception of low dosage aspirin * Has severe cardiovascular disease or symptomatic ischemic heart disease * Has hepatic decompensation * Has uncontrolled thyroid dysfunction * Has uncontrolled diabetes mellitus * Has known psychiatric or substance abuse disorders * Female is pregnant or breastfeeding * Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw * Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway * Has a known history of human immunodeficiency virus (HIV) * Has known active hepatitis B or C * Has received a live vaccine within 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration | Baseline and Week 7 | The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score. |
| Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen | Up to Week 16 | 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 experienced an AE during their regimen of neoadjuvant pembrolizumab was presented. |
| Number of Participants Who Discontinued Treatment Due to an Adverse Event | Up to 56 weeks | 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. |
| Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration | Baseline and Week 7 | The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score. |
| Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration | Baseline and Week 7 | The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab | Baseline and Week 7 | The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented. |
| Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab | Baseline and Week 7 | The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented. |
| Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab | Baseline and Week 7 | The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented. |
| Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab | Baseline and Week 7 | The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented. |
| Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab | Baseline and Week 7 | The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neoadjuvant Pembrolizumab + RCC Resection Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04. | 6 |
| RCC Resection Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04. | 4 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression prior to RCC surgery | 0 | 1 |
| Overall Study | Tumor not of the required cell histology | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | RCC Resection | Total | Neoadjuvant Pembrolizumab + RCC Resection |
|---|---|---|---|
| Age, Continuous | 55.3 Years STANDARD_DEVIATION 9.1 | 62.0 Years STANDARD_DEVIATION 8.8 | 66.5 Years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 5 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 | 0 / 6 | 0 / 1 | 1 / 4 | 0 / 1 |
| other Total, other adverse events | 4 / 4 | 1 / 1 | 0 / 3 | 1 / 1 |
| serious Total, serious adverse events | 1 / 4 | 1 / 1 | 0 / 3 | 0 / 1 |
Outcome results
Primary
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
Time frame: Baseline and Week 7
Population: The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Pembrolizumab + RCC Resection | Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration | 1 Participants |
Primary
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.
Time frame: Baseline and Week 7
Population: The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Pembrolizumab + RCC Resection | Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration | 1 Participants |
Primary
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.
Time frame: Baseline and Week 7
Population: The analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab and whose samples were evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Pembrolizumab + RCC Resection | Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration | 0 Participants |
Primary
Number of Participants Who Discontinued Treatment Due to an Adverse Event
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 56 weeks
Population: The analysis population consisted of all participants who received ≥1 dose of pembrolizumab. Participants in the RCC Resection arm only received pembrolizumab if they enrolled under protocol amendment 04. Counts were based on which course of pembrolizumab (neoadjuvant or post-resection) a participant was receiving at the time of discontinuation.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neoadjuvant Pembrolizumab + RCC Resection | Number of Participants Who Discontinued Treatment Due to an Adverse Event | During neoadjuvant pembrolizumab | 0 Participants |
| Neoadjuvant Pembrolizumab + RCC Resection | Number of Participants Who Discontinued Treatment Due to an Adverse Event | During post-RCC resection pembrolizumab | 1 Participants |
| RCC Resection | Number of Participants Who Discontinued Treatment Due to an Adverse Event | During neoadjuvant pembrolizumab | 0 Participants |
| RCC Resection | Number of Participants Who Discontinued Treatment Due to an Adverse Event | During post-RCC resection pembrolizumab | 0 Participants |
Primary
Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
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 experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.
Time frame: Up to Week 16
Population: Per protocol, the analysis population consisted of all participants who received ≥1 dose of neoadjuvant pembrolizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neoadjuvant Pembrolizumab + RCC Resection | Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen | 4 Participants |
Secondary
Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.
Time frame: Baseline and Week 7
Population: The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.
Secondary
Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
Time frame: Baseline and Week 7
Population: The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.
Secondary
Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
Time frame: Baseline and Week 7
Population: The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.
Secondary
Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab
The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.
Time frame: Baseline and Week 7
Population: The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.
Secondary
Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.
Time frame: Baseline and Week 7
Population: The analysis population was planned to consist of all participants who received ≥1 dose of neoadjuvant pembrolizumab. Due to low enrollment, there is no data to analyze for this outcome measure and therefore all participants were excluded from analysis.