Cabozantinib and Pembrolizumab for the First-Line Treatment of Advanced Liver Cancer

NCT04442581 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: RG1007034NCI-2020-0396810548
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well cabozantinib and pembrolizumab work for the first-line treatment of patients with liver cancer who are not eligible for local therapy (i.e. advanced stage). Cabozantinib may stop the growth of tumor cells by blocking some cell surface receptors and signaling pathways inside the tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer. Giving cabozantinib and pembrolizumab together may work better in treating patients with advanced liver cancer compared to cabozantinib or pembrolizumab alone.

Conditions

Advanced Hepatocellular Carcinoma; BCLC Stage B Hepatocellular Carcinoma; BCLC Stage C Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Objective Response (Complete or Partial Response)

  Will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (by blinded central review). Assessment of objective response per Response Evaluation Criteria in Solid Tumors version 1.1 of target lesions by cross sectional imaging (either CT or MRI), defined as the following: 1.) Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD, Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Overall Response Rate is defined as percentage of CR + PR.

  Assessed at baseline, every 2 cycles until cycle 4, then every 3 cycles until disease progression, up to 10 months 16 days.

Secondary Outcomes (4)

• Number of Participants With Disease Control (Complete + Partial Response + Stable Disease)

  Assessed at baseline, every 2 cycles until cycle 4, then every 3 cycles until disease progression, up to 10 months 16 days.

• Time in Months With Progression-free Survival

  Assessed at baseline, every 2 cycles until cycle 4, then every 3 cycles until disease progression, up to 10 months 16 days.

• Overall Survival Time in Months

  Survival assessed from study registration through study completion, 10 months 16 days.

• Number of Participants With Adverse Events

  Adverse events monitored from time of informed consent through the last follow-up visit or 30 days after the date of the last dose of cabozantinib or pembrolizumab treatment, whichever occurs last, up to 10 months 16 days

Study Arms (1)

Treatment (cabozantinib S-malate, pembrolizumab)

EXPERIMENTAL

Patients receive cabozantinib S-malate PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malate; Biological: Pembrolizumab

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184

Treatment (cabozantinib S-malate, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (cabozantinib S-malate, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Must have a histologically confirmed diagnosis of HCC or a non-invasive diagnosis of HCC as per the American Association for the Study of Liver Diseases (AASLD) criteria
• If available, archival tissue must be submitted
• Mixed HCC-cholangiocarcinoma is not allowed
• Patient has Barcelona Clinic Liver Cancer (BCLC) stage C disease, or BCLC stage B disease that is not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to curative treatment
• Previous locoregional therapy is allowed (e.g. surgical resection, external beam radiation, catheter-based therapy), and patients must have evidence of disease progression from locoregional therapy
• Must have measurable disease by RECIST v1.1
• Lesions that were previously radiated or ablated cannot be target lesions unless there was subsequent radiographic progression at those sites
• No prior systemic therapy for HCC. Prior chemotherapy given locally into the liver (e.g. transarterial chemoembolization \[TACE\]) is allowed
• Must have Child-Pugh class A hepatic function within 7 days prior to first dose of study intervention
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of at least 12 weeks
• Recovery to baseline or =\< grade 1 toxicities (CTCAE v5) related to any prior treatments, unless adverse events (AEs) are clinically nonsignificant and/or stable on supportive therapy
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 without granulocyte colony-stimulating factor support (within 14 days before first dose of study treatment)
• Platelets \>= 60,000/mm\^3 without transfusion (within 14 days before first dose of study treatment)
• Hemoglobin \>= 9 g/dL (\>= 90 g/L) without transfusion or erythropoietin (EPO) dependency (within 14 days before first dose of study treatment)

You may not qualify if:

• Prior treatment with any systemic therapy for HCC, including anti-VEGF therapy or any systemic investigational agent
• If the patient previously received systemic treatment for reasons other than HCC: small molecule kinase inhibitors are not allowed within 2 weeks and cytotoxic/biologic agents are not allowed within 4 weeks of study treatment
• Prior exposure to immune checkpoint inhibitors or other immunotherapeutic agents
• Currently participating in or has participated in a study of an investigational agent or device within 4 weeks prior to the first dose of study treatment
• Major surgery within 6 weeks or minor surgery (e.g. dental extraction) within 10 days prior to first dose of study treatment
• Complete wound healing from major surgery must have occurred at least 1 month before first dose and from minor surgery (e.g. simple excision, tooth extraction) at least 7 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• Local liver-directed therapy within 4 weeks of initiating study treatment
• Palliative radiation for the purpose of symptomatic relief to non-liver and non-central nervous system (CNS) disease within 2 weeks of starting treatment. Other radiation treatments within 4 weeks of starting treatment
• Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and have not had radiation pneumonitis
• Prior liver or other allogenic tissue/organ transplantation
• History of primary immunodeficiency
• Active autoimmune or inflammatory disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). This includes, but is not limited to, inflammatory bowel disease, celiac disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, Graves' disease, etc.
• The following autoimmune conditions are allowed: vitiligo or alopecia; hypothyroidism on stable hormone replacement therapy; psoriasis/eczema not requiring systemic treatment
• Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
• Chronic use of systemic steroid (in dosing exceeding 10 mg daily of prednisone equivalent) or immunosuppressive therapy or use within 14 days prior to enrollment

Sponsors & Collaborators

• University of Washington: lead
• Exelixis: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

cabozantinib; pembrolizumab

Results Point of Contact

• Title: Madeline Jacoby
• Organization: University of Washington

mjacoby@seattlecca.org

2026068246

Study Officials

• Gentry George King

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 22, 2020
• Study Start: April 20, 2021
• Primary Completion: December 13, 2021
• Study Completion: March 8, 2022
• Last Updated: April 5, 2023
• Results First Posted: April 5, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)