A Study of Abemaciclib and Cabozantinib in People With Clear Cell Renal Cell Carcinoma (ccRCC)

NCT06835972 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 24-126
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 8

Brief Summary

The researchers are doing this study to find out whether the combination of abemaciclib and cabozantinib is a safe and effective treatment for people with metastatic clear cell renal cell carcinoma (ccRCC) and translocation-associated renal cell cancer (tRCC). The researchers will test different doses of the study drugs to find the highest doses that cause few or mild side effects in participants.

Conditions

Translocation Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma

Keywords

Abemaciclib; Cabozantinib

Outcome Measures

Primary Outcomes (1)

• Maximally Tolerated Dose (MTD) (Phase Ib)

  The phase 1b portion of the trial will require between 4 and 24 patients in a 3+3 dose escalation design across four planned separate dose levels. The MTD will be defined as the dose level at which a dose limiting toxicity (DLT) occurs in at most 1 out of 6 patients in that dose level. CTCAE v5.0 will be used for toxicity evaluation.

  1 year

Secondary Outcomes (1)

• Objective Response Rate (ORR) (Phase II)

  1 year

Study Arms (1)

Abemaciclib and Cabozantinib

EXPERIMENTAL

This is a two-site single-arm open-label phase 1b/2 clinical trial evaluating abemaciclib plus cabozantinib in patients with metastatic ccRCC and tRCC that have progressed on therapy. The study comprises a dose escalation portion followed by a dose expansion phase 2 trial.

Drug: Abemaciclib; Drug: Cabozantinib

Interventions

Abemaciclib DRUG

twice a day, orally

Abemaciclib and Cabozantinib

Cabozantinib DRUG

once daily, orally

Abemaciclib and Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years at the time of informed consent
• Patient must be able to provide informed consent, or a legal authorized representative (LAR) must be identified to provide consent in cases where the patient cannot
• Signed and dated IRB-approved Informed Consent Form
• Patient must have a histologically confirmed diagnosis of metastatic stage IV clear cell renal cell carcinoma or metastatic stage IV translocation-associated renal cell carcinoma.
• Patient should have availability of archival tissue that enables definitive diagnosis of ccRCC or tRCC, per review at participating site, accompanied by an associated pathology report. Specimens can be collected by surgical resection or biopsy of the primary tumor or biopsy or resection of a metastatic lesion. NOTE: If archival tissue is unavailable, a patient can still enroll onto the study with documented confirmation from the study PI.
• Patients must have at least one extra-skeletal, extracranial measurable lesion as defined by RECIST v1.1
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patients must have received prior therapy with at least 2 approved systemic agents and a maximum of 3 prior lines of systemic therapy. Prior adjuvant therapy is permitted.
• Patient must have progressed on 1 prior PD-1 or PD-L1 targeted treatment and prior VEGFR directed TKI therapy
• Patients must have recovered to baseline or \< Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events (AEs) are clinically non-significant and/or stable on supportive therapy (See Appendix 2)
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and registration.
• The patient can swallow oral medications.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
• ANC ≥ 1500 cells/μL (without granulocyte colony stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
• WBC counts ≥ 2500/μL and ≤ 15,000/μL without G-CSF

You may not qualify if:

• Prior treatment with abemaciclib or cabozantinib.
• Receipt of any type of anti-cancer antibody, cytotoxic anticancer therapy, or any other investigational agents within 2 weeks of treatment start or 5 half-lives, whichever is shorter. For immune checkpoint inhibitors, patients must have discontinued treatment 28 days prior to trial enrollment.
• Symptomatic brain metastasis or leptomeningeal disease requiring steroid use. Patients are eligible if they are neurologically stable for 4 weeks, have completed radiation therapy or surgery, and recovered from side effects. Patients must have discontinued steroid therapy for at least 2 weeks prior to first dose of study treatment.
• Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or early stage cancers previously treated with curative intent.
• Patients requiring moderate or strong CYP3A4 inducers or inhibitors (https://druginteractions.medicine.iu.edu/MainTable.aspx).
• Patients with a history of HIV infection who are not on a stable HAART regimen and/or are requiring antimicrobials for prevention of opportunistic infections and/or have CD4 count below 250 or a detectable HIV viral load
• Patients with active hepatitis B or hepatitis C infection with detectable viral load by PCR
• Active systemic bacterial infection (requiring systemic antibiotics at time of initiating study treatment) or fungal infection.
• History of significant cardiovascular events or active cardiovascular disease; including myocardial infarction within the previous 6 months, unstable arrhythmias, unstable angina, prior sudden cardiac arrest, LVEF \< 50% by echocardiogram (ECHO).
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• Significant arterial disease (e.g., stroke, transient ischemic attack, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 470 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
• Note: If a single ECG shows a QTcF with an absolute value \> 470 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility
• Concomitant anticoagulation with coumadin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Eli Lilly and Company: collaborator
• Exelixis: collaborator

Study Sites (8)

Johns Hopkins University (Data Collection Only)

Baltimore, Maryland, 21287, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering West Harrison (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activites)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

abemaciclib; cabozantinib

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

Study Officials

• Sahil Doshi, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sahil Doshi, MD

CONTACT

646-422-4341; doshis@mskcc.org

Martin Voss, MD

CONTACT

646-888-4721

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a two-site single-arm open-label phase 1b/2 clinical trial evaluating abemaciclib plus cabozantinib in patients with metastatic ccRCC and tRCC that have progressed on therapy. The study comprises a dose escalation portion followed by a dose expansion phase 2 trial.

Study Record Dates

• First Submitted: February 14, 2025
• First Posted: February 19, 2025
• Study Start: February 14, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (8)