Trial Outcomes & Findings for Pembrolizumab With or Without Axitinib for Clear Cell Kidney Cancer in Patients Undergoing Surgery (NCT NCT04370509)

NCT ID: NCT04370509

Last Updated: 2025-11-19

Results Overview

TIICs will be analyzed in pre- and post-pembrolizumab-based treatment tumor specimens. The proportion of participants with a \>=2-fold increase (from pre- to post-treatment) in the number of TIICs will be calculated.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Baseline to cytoreductive nephrectomy (CN)/metastasectomy (MET), up to 1 year

Results posted on

2025-11-19

Participant Flow

The study was closed to enrollment by the sponsor before enrollment in Cohort B was made available to participants. Therefore, no participants could be enrolled in Cohort B.

Participant milestones

Participant milestones
Measure
Cohort A (Pembrolizumab Monotherapy)
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with progressive disease (PD) may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Cohort B (Pembrolizumab + VEGF-TKI)
Preoperative treatment consists of 200 mg pembrolizumab IV on day 1 of each cycle, and 5mg axitinib (a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)) orally (PO) twice a day (BID) on days 1-42 of each cycle. Axitinib maybe titered in select patients after cycle 1. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of pre-operative treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with an R0 or R1 resection receive 400 mg pembrolizumab and 1, 3, 5, 7 or 10 mg axitinib PO BID every 42 days for up to 9 cycles (1 year), and patients with an R2 resection receive pembrolizumab IV and axitinib PO BID every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Overall Study
STARTED
6
0
Overall Study
Completed Cytoreductive Nephrectomy (CN) or Metastasectomy (MET)
5
0
Overall Study
Received 1 Year of Pembrolizumab
4
0
Overall Study
COMPLETED
4
0
Overall Study
NOT COMPLETED
2
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Cohort A (Pembrolizumab Monotherapy)
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with progressive disease (PD) may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Cohort B (Pembrolizumab + VEGF-TKI)
Preoperative treatment consists of 200 mg pembrolizumab IV on day 1 of each cycle, and 5mg axitinib (a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)) orally (PO) twice a day (BID) on days 1-42 of each cycle. Axitinib maybe titered in select patients after cycle 1. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of pre-operative treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with an R0 or R1 resection receive 400 mg pembrolizumab and 1, 3, 5, 7 or 10 mg axitinib PO BID every 42 days for up to 9 cycles (1 year), and patients with an R2 resection receive pembrolizumab IV and axitinib PO BID every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Overall Study
Adverse Event
1
0
Overall Study
Did not receive post-op Pembrolizumab
1
0

Baseline Characteristics

Pembrolizumab With or Without Axitinib for Clear Cell Kidney Cancer in Patients Undergoing Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cohort A (Pembrolizumab Monotherapy)
n=6 Participants
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Cohort B (Pembrolizumab + VEGF-TKI)
Preoperative treatment consists of 200 mg pembrolizumab IV on day 1 of each cycle, and 5mg axitinib (a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)) PO BID on days 1-42 of each cycle. Axitinib maybe titered in select patients after cycle 1. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of pre-operative treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with an R0 or R1 resection receive 400 mg pembrolizumab and 1, 3, 5, 7 or 10 mg axitinib PO BID every 42 days for up to 9 cycles (1 year), and patients with an R2 resection receive pembrolizumab IV and axitinib PO BID every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Total
n=6 Participants
Total of all reporting groups
Age, Customized
40-49 years old
1 Participants
0 Participants
n=4 Participants
1 Participants
n=8 Participants
Age, Customized
50-59 years old
1 Participants
0 Participants
n=4 Participants
1 Participants
n=8 Participants
Age, Customized
60-69 years old
1 Participants
0 Participants
n=4 Participants
1 Participants
n=8 Participants
Age, Customized
70-79 years old
3 Participants
0 Participants
n=4 Participants
3 Participants
n=8 Participants
Sex: Female, Male
Female
2 Participants
0 Participants
n=4 Participants
2 Participants
n=8 Participants
Sex: Female, Male
Male
4 Participants
0 Participants
n=4 Participants
4 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
0 Participants
n=4 Participants
2 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
2 Participants
0 Participants
n=4 Participants
2 Participants
n=8 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants
0 Participants
n=4 Participants
2 Participants
n=8 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
0 Participants
n=4 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
Asian
1 Participants
0 Participants
n=4 Participants
1 Participants
n=8 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
0 Participants
n=4 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
Black or African American
0 Participants
0 Participants
n=4 Participants
0 Participants
n=8 Participants
Race (NIH/OMB)
White
3 Participants
0 Participants
n=4 Participants
3 Participants
n=8 Participants
Race (NIH/OMB)
More than one race
1 Participants
0 Participants
n=4 Participants
1 Participants
n=8 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
0 Participants
n=4 Participants
1 Participants
n=8 Participants
Region of Enrollment
United States
6 participants
6 participants
n=8 Participants

PRIMARY outcome

Timeframe: Baseline to cytoreductive nephrectomy (CN)/metastasectomy (MET), up to 1 year

Population: The analysis for this endpoint could not be completed due to insufficient funds for the laboratory experiments to determine the number of tumor-infiltrating immune cells (TIICs), when the collaborating sponsor (Merck Sharp and Dohme) terminated the study prematurely. Therefore, no plans currently exist to fund analysis of this endpoint in the future.

TIICs will be analyzed in pre- and post-pembrolizumab-based treatment tumor specimens. The proportion of participants with a \>=2-fold increase (from pre- to post-treatment) in the number of TIICs will be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 year

Objective response rate in pre-operative pembrolizumab-based therapy in participants with advanced renal cell carcinoma (RCC) will be defined as proportion of participants who obtain a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors 1.1 modified to allow a maximum of 10 target lesions or 5 target lesions per organ. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; Partial Response (PR), \>=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure
Cohort A (Pembrolizumab Monotherapy)
n=6 Participants
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Objective Response Rate (ORR) in Pre-operative Pembrolizumab-based Therapy
0 proportion of participants

SECONDARY outcome

Timeframe: Up to 1 year

The DFS for continued pembrolizumab-based therapy in participants with advanced RCC will be assessed in participants who achieve CR, PR, or stable disease (SD) followed by R0 resection, and is defined as the proportion of those participants who remain disease-free at the end of the 1 year continued treatment period (1-year DFS rate)

Outcome measures

Outcome measures
Measure
Cohort A (Pembrolizumab Monotherapy)
n=4 Participants
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Disease-Free Survival Rate (DFS) at 1 Year for Participants Who Obtain CR or PR/SD With R0 Resection and Are Treated 1 Year of Pembrolizumab-based Therapy
1.0 proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

The DFS for continued pembrolizumab-based therapy in participants with advanced RCC will be assessed in participants who achieve CR, PR, or stable disease (SD) followed by R0 resection, and is defined as the proportion of those participants who remain disease-free at 1 year following the end of the continued treatment period (2-year DFS rate)

Outcome measures

Outcome measures
Measure
Cohort A (Pembrolizumab Monotherapy)
n=4 Participants
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Disease-Free Survival Rate (DFS) at 2 Years for Participants Who Obtain CR or PR/SD With R0 Resection and Are Treated 1 Year of Pembrolizumab-based Therapy
0.5 proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

In participants who achieve CR, PR or stable disease (SD) followed by R0 resection, median time participants remain disease-free will be reported using the Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure
Cohort A (Pembrolizumab Monotherapy)
n=4 Participants
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Median DFS for Participants Who Obtain CR or PR/SD With R0 Resection and Are Treated 1 Year of Pembrolizumab-based Therapy
651 days
Interval 602.0 to
There were insufficient number of events so the upper limit could not be reached.

SECONDARY outcome

Timeframe: Up to 1 year

Population: No participants achieved PR/SD with residual disease; therefore, data were not collected from any participants.

PFS for participants who achieve PR/SD with residual disease following CN/MET and are also treated with 1 year of pembrolizumab-based therapy is defined as the proportion of participants who remain progression-free at the end of the 1 year continued treatment period (1-year PFS rate)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Population: No participants achieved PR/SD with residual disease; therefore, data were not collected from any participants.

PFS in participants who achieve PR/SD with residual disease following CN/MET and are also treated with 1 year of pembrolizumab-based therapy is defined as the proportion of participants who remain progression-free at 1 year following the end of the continued treatment period (2-year PFS rate)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Population: No participants achieved PR/SD with residual disease; therefore, data were not collected from any participants.

The Median PFS for participants who obtain PR/SD and have residual disease following CN/MET and are treated with 1 year of pembrolizumab-based therapy will be reported as the median time participants remain progression-free using the Kaplan-Meier estimate.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

Adverse events classified as being definitely, possibly, or probably related to study treatment will be assessed and reported using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0

Outcome measures

Outcome measures
Measure
Cohort A (Pembrolizumab Monotherapy)
n=6 Participants
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Number of Participants Reporting Treatment-related Adverse Events
6 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: One participant withdrew from the study prior to receiving surgery and was excluded from this endpoint analysis.

The number of participants reporting surgical complications by grade using the Clavien-Dindo Classification of Surgical Complications will be reported.

Outcome measures

Outcome measures
Measure
Cohort A (Pembrolizumab Monotherapy)
n=5 Participants
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Number of Participants Reporting Surgical Complications
0 Participants

Adverse Events

Cohort A (Pembrolizumab Monotherapy)

Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Cohort A (Pembrolizumab Monotherapy)
n=6 participants at risk
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders
Colitis
16.7%
1/6 • Number of events 1 • Up to 2 years
Renal and urinary disorders
Hematuria
16.7%
1/6 • Number of events 1 • Up to 2 years
Blood and lymphatic system disorders
Anemia
16.7%
1/6 • Number of events 1 • Up to 2 years
Hepatobiliary disorders
Cholecystitis
16.7%
1/6 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders
Myositis
16.7%
1/6 • Number of events 1 • Up to 2 years

Other adverse events

Other adverse events
Measure
Cohort A (Pembrolizumab Monotherapy)
n=6 participants at risk
Preoperative treatment consists of 200mg pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles (9 weeks). Within 14-21 days following the end of treatment, patients undergo standard of care CN or MET. Patients with PD may undergo CN or MET per physician discretion. Within 21-42 days after surgery, patients with R0 resection or R1 resection receive 400 mg pembrolizumab every 42 days for up to 9 cycles (1 year) and patients with R2 resection receive pembrolizumab every 42 days for up to 18 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Investigations
Creatinine increased
50.0%
3/6 • Number of events 4 • Up to 2 years
Investigations
Weight loss
16.7%
1/6 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders
Hyponatremia
33.3%
2/6 • Number of events 2 • Up to 2 years
Metabolism and nutrition disorders
Anorexia
16.7%
1/6 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders
Hypercalcemia
16.7%
1/6 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders
Hypokalemia
16.7%
1/6 • Number of events 1 • Up to 2 years
Nervous system disorders
Paresthesia
33.3%
2/6 • Number of events 2 • Up to 2 years
Nervous system disorders
Dysarthria
16.7%
1/6 • Number of events 1 • Up to 2 years
Nervous system disorders
Syncope
16.7%
1/6 • Number of events 1 • Up to 2 years
Respiratory, thoracic and mediastinal disorders
Cough
50.0%
3/6 • Number of events 6 • Up to 2 years
Respiratory, thoracic and mediastinal disorders
Sore throat
16.7%
1/6 • Number of events 1 • Up to 2 years
Skin and subcutaneous tissue disorders
Pruritus
33.3%
2/6 • Number of events 2 • Up to 2 years
Skin and subcutaneous tissue disorders
Dry skin
16.7%
1/6 • Number of events 1 • Up to 2 years
Skin and subcutaneous tissue disorders
Rash acneiform
16.7%
1/6 • Number of events 1 • Up to 2 years
Skin and subcutaneous tissue disorders
Rash maculo-papular
16.7%
1/6 • Number of events 1 • Up to 2 years
Blood and lymphatic system disorders
Anemia
33.3%
2/6 • Number of events 4 • Up to 2 years
Renal and urinary disorders
Hematuria
33.3%
2/6 • Number of events 3 • Up to 2 years
Cardiac disorders
Myocarditis
16.7%
1/6 • Number of events 1 • Up to 2 years
Endocrine disorders
Adrenal insufficiency
16.7%
1/6 • Number of events 1 • Up to 2 years
Endocrine disorders
Hypophysitis
16.7%
1/6 • Number of events 1 • Up to 2 years
Infections and infestations
Infections and infestations - Other, specify
16.7%
1/6 • Number of events 1 • Up to 2 years
Injury, poisoning and procedural complications
Fall
16.7%
1/6 • Number of events 2 • Up to 2 years
Vascular disorders
Thromboembolic event
16.7%
1/6 • Number of events 1 • Up to 2 years
Hepatobiliary disorders
Cholecystitis
16.7%
1/6 • Number of events 1 • Up to 2 years
General disorders
Fatigue
33.3%
2/6 • Number of events 2 • Up to 2 years
General disorders
Pain
16.7%
1/6 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders
Arthralgia
50.0%
3/6 • Number of events 10 • Up to 2 years
Musculoskeletal and connective tissue disorders
Pain in extremity
50.0%
3/6 • Number of events 4 • Up to 2 years
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
33.3%
2/6 • Number of events 3 • Up to 2 years
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
16.7%
1/6 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
16.7%
1/6 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders
Myositis
16.7%
1/6 • Number of events 1 • Up to 2 years
Gastrointestinal disorders
Diarrhea
33.3%
2/6 • Number of events 2 • Up to 2 years
Gastrointestinal disorders
Abdominal distension
16.7%
1/6 • Number of events 1 • Up to 2 years
Gastrointestinal disorders
Abdominal pain
16.7%
1/6 • Number of events 1 • Up to 2 years
Gastrointestinal disorders
Dysphagia
16.7%
1/6 • Number of events 1 • Up to 2 years
Gastrointestinal disorders
Nausea
16.7%
1/6 • Number of events 1 • Up to 2 years
General disorders
Edema limbs
33.3%
2/6 • Number of events 7 • Up to 2 years

Additional Information

Dr. David Oh, MD, PhD

University of California, San Francisco

Phone: (415) 476-1000

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place