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

NCT04370509 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 197017NCI-2020-02128
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab with or without standard of care axitinib works in treating patients with clear cell kidney cancer that has spread to nearby tissues or lymph nodes (locally advanced) or other places in the body (metastatic) who are undergoing surgery. Pembrolizumab is an antibody that is designed to bind to and block the activity of PD-1, a molecule in the body that may be responsible for inhibiting the body's immune response against cancer cells. Axitinib is a type of drug known as a tyrosine kinase inhibitor. Tyrosine kinase inhibitors work by blocking enzymes called tyrosine kinases. These enzymes may be too active or found at high levels in some types of cancer cells and blocking them may help keep cancer cells from growing. Giving pembrolizumab with or without axitinib may work better in controlling the cancer and decrease the likelihood of it coming back following surgery in patients with kidney cancer compared to usual treatment (surgery followed by chemotherapy and/or radiation therapy).

Conditions

Metastatic Clear Cell Renal Cell Carcinoma; Recurrent Clear Cell Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8; Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With >= 2-fold Increase in the Number of Tumor-infiltrating Immune Cells (TIICs)

  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.

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

Secondary Outcomes (9)

• Objective Response Rate (ORR) in Pre-operative Pembrolizumab-based Therapy

  Up to 1 year

• 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

  Up to 1 year

• 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

  Up to 2 years

• Median DFS for Participants Who Obtain CR or PR/SD With R0 Resection and Are Treated 1 Year of Pembrolizumab-based Therapy

  Up to 2 years

• Progression-free Survival Rate (PFS) at 1 Year for Participants Who Obtain PR/SD and Have Residual Disease Following CN/MET and Are Treated With 1 Year of Pembrolizumab-based Therapy

  Up to 1 year

Study Arms (2)

Cohort A (Pembrolizumab monotherapy)

EXPERIMENTAL

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.

Procedure: Cytoreductive Nephrectomy (CN); Procedure: Metastasectomy (MET); Biological: Pembrolizumab

Cohort B (Pembrolizumab + VEGF-TKI)

EXPERIMENTAL

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.

Drug: Axitinib (VEGF-TKI); Procedure: Cytoreductive Nephrectomy (CN); Procedure: Metastasectomy (MET); Biological: Pembrolizumab

Interventions

Axitinib (VEGF-TKI) DRUG

Given PO

Also known as: AG-013736, AG013736, Inlyta

Cohort B (Pembrolizumab + VEGF-TKI)

Cytoreductive Nephrectomy (CN) PROCEDURE

Undergo CN

Also known as: Cytoreduction, Nephrectomy

Cohort A (Pembrolizumab monotherapy); Cohort B (Pembrolizumab + VEGF-TKI)

Metastasectomy (MET) PROCEDURE

Undergo MET

Also known as: Metastasectomy

Cohort A (Pembrolizumab monotherapy); Cohort B (Pembrolizumab + VEGF-TKI)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Cohort A (Pembrolizumab monotherapy); Cohort B (Pembrolizumab + VEGF-TKI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed RCC with a clear cell component.
• Locally advanced or metastatic disease (primary intact or status post nephrectomy with recurrent disease)
• Planned CN and/or MET.
• Must have a tumor lesion amenable to biopsy at pre-treatment and subjects must consent to acquisition of fresh tumor specimens obtained using the following approaches:
• Core biopsy.
• Nephrectomy.
• Metastasectomy (MET). Note: Subjects who undergo nephrectomy or metastasectomy prior to study enrollment must still have measurable disease (RECIST 1.1) that is amenable to cytoreductive nephrectomy or metastasectomy to be eligible for study participation.
• Fine needle aspiration (FNA) specimens are not acceptable.
• Measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Subject (or legally acceptable representative if applicable) must provide written informed consent for the trial.
• At least 18 years of age on day of signing informed consent.
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Adequate organ function as defined in Table 1; all screening labs should be performed within 10 days of treatment initiation.
• Absolute neutrophil count (ANC) \>= 1,500/microliter (uL)
• Platelets \>= 100,000/uL.

You may not qualify if:

• RCC WITHOUT a clear cell component.
• Prior systemic therapy for the treatment of RCC.
• No measurable disease (e.g. only bone metastases).
• Not a candidate for CN and/or MET.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• \* Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since the last dose of the previous investigational agent
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Known history of active Bacillus tuberculosis (TB).
• Severe hypersensitivity (\>= grade 3) to pembrolizumab/axitinib or any of their excipients.
• Prior systemic anti-cancer monoclonal antibody (mAb), targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study treatment (Day 1).
• Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =\< grade 1 or baseline. Participants with =\< grade 2 neuropathy may be eligible.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Known additional malignancy that is progressing or has required active treatment within the past 2 years.
• \* Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded

Sponsors & Collaborators

• University of California, San Francisco: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Carcinoma, Renal Cell

Interventions

Axitinib; Cytoreduction Surgical Procedures; Nephrectomy; Metastasectomy; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Limitations and Caveats

The study was terminated earlier than expected.

Results Point of Contact

• Title: Dr. David Oh, MD, PhD
• Organization: University of California, San Francisco

david.oh@ucsf.edu

(415) 476-1000

Study Officials

• David Y Oh, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2020
• First Posted: May 1, 2020
• Study Start: February 9, 2021
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: November 19, 2025
• Results First Posted: November 5, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)