Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma

Completed · Phase 1/Phase 2

Conditions studied: Metastatic Renal Cell Carcinoma

In brief

This is a phase I/II open-label study designed to evaluate the combination of pembrolizumab and cabozantinib in subjects with locally advanced, recurrent, or metastatic renal cell carcinoma. Sequential dose escalation of cabozantinib with standard dose pembrolizumab will occur in the phase I dose escalation part of the study to determine the recommended phase 2 dose (RP2D). Subsequently, subjects will receive cabozantinib at the RP2D in combination with pembrolizumab in the phase II dose expansion part of the study.

Key facts

Study ID

NCT03149822

Run by

University of Colorado, Denver

People needed

45

Starts

2017-09-28

Expected to finish

2024-02-16

Last updated by the study team

2025-03-13

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects must have histological or cytological documentation of renal cell carcinoma
• Subjects must have locally advanced, recurrent, or metastatic disease.
• Be willing and able to provide written informed consent/assent for the trial.
• Stated willingness to complywith all study procedures and be available for the duration of the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable or evaluable disease based on RECIST 1.1.
• Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
• Confirmed availability of representative archival tumor specimens in paraffin blocks (preferred) or ≥ 10 unstained slides, with an associated pathology report.
• Acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, or punch biopsies for cutaneous, subcutaneous, or mucosal lesions.
• Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable.
• A subject with insufficient or unavailable archival tissue may be eligible, upon discussion with the Principal Investigator, if the subject is willing to consent to undergo a pretreatment core, punch, or excisional/incisional biopsy sample collection of the tumor.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined by desired lab values.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if…

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroiderapy equivalent to ≥ 10 mg/day of prednisone, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Has had prior treatment with pembrolizumab.
• Has had prior treatment with cabozantinib.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Note: Subjects with stable, treated hypothyroidism or adrenal insufficiency may qualify for the study
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Subjects with hypertension managed with medication are an exception to this criterion and may qualify for the study.
• Subjects with ≤ Grade 2 endocrinopathy (e.g. hypothyroidism or adrenal insufficiency managed with medication) are an exception to this criterion and may qualify for the study.
• Has had major surgery within 4 weeks or minor surgery within 2 weeks prior to study Day 1. Subjects must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Prior treatment with immune checkpoint inhibitors is allowed, provided that no treatment-related Grade ≥ 3 adverse events (other than Grade 3 endocrinopathy managed with replacement therapy) were observed and at least a minimum of 28 days have elapsed between the last dose of prior treatment and the proposed Cycle 1 Day 1.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, carcinoma in situ or superficial bladder cancer, low-grade prostate cancer, intraductal papillary mucinous neoplasm (IPMN), and other low grade cancers that is suitable for active surveillance in the opinion of the investigator.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Active CNS metastases will be defined as brain lesions that 1) require intervention with surgery, stereotactic radiosurgery (SRS), or whole brain radiotherapy (WBRT) or 2) require anti-epileptic therapy, systemic steroid treatment, or intrathecal therapy. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks after completion of focal therapy for brain metastases and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
• Has history of solid organ transplantation.
• Has history of osteonecrosis of the jaw.
• Has history of reversible posterior leukoencephalopathy syndrome.
• Has history of wound dehiscence or complications requiring medical intervention within 6 months of study entry.
• Has history of (non-infectious) pneumonitis that required steroids or active, non- infectious pneumonitis.
• Has an active infection requiring systemic therapy with IV antibiotics.
• Has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias.

Where it is running

• University of Colorado Denver — Aurora, Colorado, United States
• Memorial Hospital Central — Colorado Springs, Colorado, United States
• Poudre Valley Hospital — Fort Collins, Colorado, United States
• Highlands Ranch Hospital — Highlands Ranch, Colorado, United States
• UCHealth Lone Tree Medical Center — Lone Tree, Colorado, United States

Full record on ClinicalTrials.gov

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