Testing the Addition of an Anti-Cancer Drug, Cabozantinib to the Immunotherapy Drug Cemiplimab (REGN2810), in Adolescents and Adults With Advanced Adrenocortical Cancer

NCT06900595 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2025-02021A092204U10CA180821
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 65

Brief Summary

This phase II trial compares the effect of giving cabozantinib with or without cemiplimab in patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), and that cannot be removed by surgery (unresectable) or that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib with cemiplimab may kill more tumor cells in patients with locally advanced unresectable or recurrent/metastatic adrenocortical cancer.

Conditions

Locally Advanced Adrenal Cortical Carcinoma; Metastatic Adrenal Cortical Carcinoma; Recurrent Adrenal Cortical Carcinoma; Stage III Adrenal Cortical Carcinoma AJCC v8; Stage IV Adrenal Cortical Carcinoma AJCC v8; Unresectable Adrenal Cortical Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Will be analyzed using an intention-to-treat approach. Kaplan-Meier methodology will be used to estimate the distributions for the treatment arms. The hazard ratio, median PFS, and estimated PFS rates at 5, 10 and 15 months will be estimated along with corresponding 95% confidence intervals. A one-sided log rank-test will be used to compare the PFS distributions between the two treatment arms.

  From registration to either progression or death, assessed up to 4 years post-registration

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 4 years post-registration

• Objective response rate

  Up to 4 years post-registration

• Duration of response

  From first date of the patient achieving either a complete or partial response and progression (via RECIST v 1.1), assessed up to 4 years post-registration

• Time to progression

  From registration date and progression date, assessed up to 4 years post-registration

• Overall survival

  From registration to death, assessed up to 4 years post-registration

Other Outcomes (1)

• Median PFS for patients who cross over

  From re-registration to progression or death, assessed up to 4 years post-registration

Study Arms (2)

Arm A (cabozantinib)

EXPERIMENTAL

Patients receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study. Upon disease progression, patients may elect to crossover to receive combination therapy on Arm B.

Procedure: Biospecimen Collection; Drug: Cabozantinib; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Arm B (cabozantinib and cemiplimab)

EXPERIMENTAL

Patients receive cemiplimab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Drug: Cabozantinib; Biological: Cemiplimab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (cabozantinib); Arm B (cabozantinib and cemiplimab)

Cabozantinib DRUG

Given PO

Arm A (cabozantinib); Arm B (cabozantinib and cemiplimab)

Cemiplimab BIOLOGICAL

Given IV

Also known as: Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN 2810, REGN-2810, REGN2810

Arm B (cabozantinib and cemiplimab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A (cabozantinib); Arm B (cabozantinib and cemiplimab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (cabozantinib); Arm B (cabozantinib and cemiplimab)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• STEP 1: Patients must have documented histologically or cytologically confirmed adrenocortical carcinoma
• STEP 1: Locally advanced unresectable or recurrent/metastatic disease
• STEP 1: Evaluable disease as defined by RECIST v 1.1
• STEP 1: Up to 3 prior lines of systemic therapy will be allowed in the unresectable/recurrent/metastatic setting. Treatment naïve patients will be allowed.
• Note: Combination etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) is considered 1 line of therapy. For patients who received mitotane ≤ 6 months prior to registration, mitotane should be discontinued 28 days prior to study registration AND a mitotane level must be documented to be \< 2 mg/L prior to registration. Patients who have received mitotane within 6 months of enrollment and who have mitotane levels ≥ 2 mg/L will not be eligible to enroll
• STEP 1: No prior treatment with cabozantinib or other cMET inhibitors, or anti-CTLA-4, or anti-PD-1/PD-L1 therapy
• STEP 1: Prior external beam radiation therapy (any area radiated within a month prior to study registration cannot be used as an index lesion and only growth outside of the radiation field can be considered for disease progression), systemic cytotoxic chemotherapy, targeted therapies will be allowed, as long as not administered within 14 days before study registration, and provided any acute treatment-related associated toxicities have recovered to ≤ grade 1 except for alopecia, peripheral neuropathy or other residual toxicities that are not deemed clinically significant
• STEP 1: Potential trial participants should have recovered from clinically significant adverse events, and wound healing is clinically adequate of their most recent therapy/intervention prior to enrollment
• STEP 1: Age 12 years and above; and BSA ≥ 1.2m\^2
• STEP 1:
• Eastern Cooperative Oncology Group (ECOG) performance 0 - 2 (age 18 and above); or
• Patients 12 to \<16 years of age will be assessed by the Lansky scale and should have a score ≥ 50; or
• Patients ≥ 16 to \<18 years of age will be assessed by the Karnofsky scale, and should have a score ≥ 50
• STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mcL without colony stimulating factor support within 2 weeks prior
• Transfusion support is allowed if ≥ 7 days from obtaining required initial laboratory

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (65)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Carle at The Riverfront

Danville, Illinois, 61832, United States

RECRUITING

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, 60115, United States

RECRUITING

Carle Physician Group-Effingham

Effingham, Illinois, 62401, United States

RECRUITING

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134, United States

RECRUITING

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois, 60026, United States

RECRUITING

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois, 60030, United States

RECRUITING

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

RECRUITING

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938, United States

RECRUITING

Carle BroMenn Medical Center

Normal, Illinois, 61761, United States

RECRUITING

Carle Cancer Institute Normal

Normal, Illinois, 61761, United States

RECRUITING

Northwestern Medicine Oak Brook

Oak Brook, Illinois, 60523, United States

RECRUITING

Northwestern Medicine Orland Park

Orland Park, Illinois, 60462, United States

RECRUITING

Memorial Hospital East

Shiloh, Illinois, 62269, United States

RECRUITING

Carle Cancer Center

Urbana, Illinois, 61801, United States

RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, 50023, United States

RECRUITING

Saint Anthony Regional Hospital

Carroll, Iowa, 51401, United States

RECRUITING

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, 50325, United States

RECRUITING

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, 50309, United States

RECRUITING

Broadlawns Medical Center

Des Moines, Iowa, 50314, United States

RECRUITING

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, 50314, United States

RECRUITING

UI Healthcare Mission Cancer and Blood - Fort Dodge

Fort Dodge, Iowa, 50501, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa, 50263, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

RECRUITING

CoxHealth South Hospital

Springfield, Missouri, 65807, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

RECRUITING

Nebraska Medicine-Bellevue

Bellevue, Nebraska, 68123, United States

RECRUITING

Nebraska Medicine-Village Pointe

Omaha, Nebraska, 68118, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Duke Cancer Center Cary

Cary, North Carolina, 27518, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Duke Cancer Center Raleigh

Raleigh, North Carolina, 27609, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, 29316, United States

RECRUITING

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

RECRUITING

Prisma Health Cancer Institute - Easley

Easley, South Carolina, 29640, United States

RECRUITING

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

RECRUITING

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, 29605, United States

RECRUITING

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605, United States

RECRUITING

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, 29615, United States

RECRUITING

Prisma Health Cancer Institute - Greer

Greer, South Carolina, 29650, United States

RECRUITING

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, 29672, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, 23235, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Specimen Handling; cabozantinib; cemiplimab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Bhavana Konda

  Alliance for Clinical Trials in Oncology

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: March 28, 2025
• Study Start: February 22, 2026
• Primary Completion (Estimated): June 2, 2029
• Study Completion (Estimated): June 2, 2029
• Last Updated: April 14, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (65)