NCT05136196|RecruitingPhase 2FDA Drug

BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study

Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab (NSC#748726) (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants With Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2021-12653S2101U10CA180888

Study Type

interventional

Target

150

Locations

1 country

Sites

222

Timeline

RegisteredNov 2021

StartedDec 2022

CompletionJan 2027

Brief Summary

This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are "tumor mutational burden" and "tumor inflammation signature." Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

150

participants targeted

Target at P75+ for phase_2

Timeline

7mo left

Started Dec 2022

Typical duration for phase_2

Geographic Reach

1 country

222 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

4.1 years study duration

Study Progress87%

Dec 2022Jan 2027

First Submitted

Initial submission to the registry

November 25, 2021

Completed

4 days until next milestone

First Posted

Study publicly available on registry

November 29, 2021

Completed

1 year until next milestone

Study Start

First participant enrolled

December 6, 2022

Completed

4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2027

Last Updated

June 5, 2026

Status Verified

March 1, 2026

Enrollment Period

4.1 years

First QC Date

November 25, 2021

Last Update Submit

June 4, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

Biomarker results turnaround time
A biomarker turnaround time estimate of at least 75% within 21 days will be considered successful with respect to feasibility. For melanoma participants, turnaround time is defined as the time-period between date of tissue submission by the site to central repository and date the site was sent notification of participant molecular group determination. For head and neck squamous cell carcinoma (HNSCC) participants, turnaround time is defined as the time-period between date of tissue submission by the site to central repository and one day after both results have been received by the Southwest Oncology Group Statistics and Data Management Center to simulate when the site would have received notification of participant molecular group determination.
Within 21 days
Objective response rate
Confirmed and unconfirmed complete and partial responses) in molecular subgroups. Will assess biomarker response association. To test this association, will consider combination of biomarkers coded as 0 = Lo/Lo, 1 = Lo/Hi or Hi/Lo, and 2 = Hi/Hi. Assume each biomarker level is associated with an odds-ratio of approximately 3.1 (for example, corresponding to a difference in response rate of 5 percent to 14 percent from Lo/Lo to Lo/Hi or Hi/Lo). For the melanoma cohort, with approximately equal sized biomarker combination subgroups, a one-sided 0.10 level test for trend using (0,1,2) coding with logistic regression has a power of 80%. The same analysis for HNSCC will have lower power for the same effect size due to the unequal frequencies in the subgroups defined by the biomarkers. We will also conduct disease-by-biomarker interaction tests; however, there will be limited power to detect even to detect relatively large interaction parameters.
At the end of stage I

Secondary Outcomes (5)

Rate and profile of >= grade 3 treatment-related adverse events
Up to 2 years
Disease control rate
Up to 2 years
Progression-free survival
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years
Overall survival
From date of registration to date of death due to any cause, assessed up to 2 years
Turnaround time for the Tumor Inflammation Score in stage II
Assessed within 21 days

Other Outcomes (1)

Additional markers of response or resistance
Up to 2 years

Study Arms (1)

Treatment (nivolumab and cabozantinib)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and cabozantinib PO daily. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans and collection of blood samples throughout the trial. Patients undergo a tumor biopsy during screening and optionally during follow-up.

Procedure: Biopsy ProcedureProcedure: Biospecimen CollectionDrug: Cabozantinib S-malateProcedure: Computed TomographyProcedure: Magnetic Resonance ImagingBiological: Nivolumab