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

NCT03149822 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 16-2300.ccNCI-2017-01777
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Metastatic Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Efficacy of Pembrolizumab and Cabozantinib Based on Objective Response Rate

  Measured through the complete response (CR) + partial response (PR)\] of pembrolizumab and cabozantinib when administered in combination in subjects with locally advanced or metastatic renal cell carcinoma. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Beginning of study to end of study, up to 5 years

Secondary Outcomes (6)

• Maximally Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

  Throughout Cycle 1, up to 21 days

• Dose Limiting Toxicities

  Throughout Cycle 1, up to 21 days

• Progression-Free Survival

  Beginning of study to end of study, or death, whichever comes first, up to 5 years

• Overall Survival

  Beginning of study to end of study, or death, whichever comes first, up to 5 years

• Disease Control Rate (DCR), AKA Clinical Benefit Rate (CBR)

  Beginning of study to end of study, or death, whichever comes first, up to 5 years

Study Arms (3)

Phase 1: Pembrolizumab 200 mg plus Cabozantinib 40mg

EXPERIMENTAL

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 40 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Drug: Cabozantinib; Drug: Pembrolizumab

Phase 1: Pembrolizumab 200 mg plus Cabozantinib 60mg

EXPERIMENTAL

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib 60 mg orally once daily until disease progression, unacceptable toxicity, or consent withdrawal.

Drug: Cabozantinib; Drug: Pembrolizumab

Phase 2: Pembrolizumab 200 mg plus Cabozantinib at the RP2D

EXPERIMENTAL

Pembrolizumab 200 mg intravenous (IV) infusion on day 1 of each 21-day cycle in combination with cabozantinib at the RP2D orally once daily for up to 35 cycles, until disease progression, unacceptable toxicity, or consent withdrawal. All participants who stop pembrolizumab after 35 cycles with SD or better may be eligible for up to an additional 17 cycles (approximately 1 year) of pembrolizumab treatment if they progress after stopping pembrolizumab from the initial treatment phase.

Drug: Cabozantinib; Drug: Pembrolizumab

Interventions

Cabozantinib DRUG

Pharmaceutical form: tablets Route of administration: oral

Also known as: Cabometyx

Phase 1: Pembrolizumab 200 mg plus Cabozantinib 40mg; Phase 1: Pembrolizumab 200 mg plus Cabozantinib 60mg; Phase 2: Pembrolizumab 200 mg plus Cabozantinib at the RP2D

Pembrolizumab DRUG

Pharmaceutical form: solution Route of administration: injection

Also known as: MK-3475, Keytruda

Phase 1: Pembrolizumab 200 mg plus Cabozantinib 40mg; Phase 1: Pembrolizumab 200 mg plus Cabozantinib 60mg; Phase 2: Pembrolizumab 200 mg plus Cabozantinib at the RP2D

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Memorial Hospital Central

Colorado Springs, Colorado, 80909, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80528, United States

Location

Highlands Ranch Hospital

Highlands Ranch, Colorado, 80129, United States

Location

UCHealth Lone Tree Medical Center

Lone Tree, Colorado, 80124, United States

Location

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MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

cabozantinib; 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

Results Point of Contact

• Title: Dr. Elaine Lam
• Organization: University of Colorado Hospital

elaine.lam@cuanschutz.edu

7208480723

Study Officials

• Elaine Lam, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 11, 2017
• Study Start: September 28, 2017
• Primary Completion: December 14, 2022
• Study Completion: February 16, 2024
• Last Updated: March 13, 2025
• Results First Posted: October 17, 2023

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)