A Study of Combining Cabozantinib and Atezolizumab for Advanced/Metastatic NSCLC (Cabatezo-1)

NCT05859217 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT-2021-Cabatezo-1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

NSCLC patients with low expression level of PD-L1, esp. those with its level less than 1%, do not derive much benefit from anti-PD-1/L1 therapy (e.g. atezoilzumab). In this study, investigators hypothesize that the combination of cabozantinib (a multi-kinase inhibitor) and atezolizumab will result in better therapeutic value.

Conditions

Lung Cancer; NSCLC Stage IV; Metastatic NSCLC - Non-Small Cell Lung Cancer; Advanced NSCLC

Keywords

Cancer immunotherapy; anti-angiogenesis; Investigator-initiated clinical trial

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  From baseline to End of Treatment (EOT) due to disease progression using RECIST criteria 1.1

  through study completion, an average of 1 year

Secondary Outcomes (4)

• Duration of response (DOR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Progression-free survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Overall survival (OS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Drug Safety

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Study Arms (1)

Cabozantinib and Atezolizumab

EXPERIMENTAL

Cabozantinib 40mg po daily + Atezolizumab 1200mg iv on day 1; 1 cycle = 21 days

Drug: Cabozantinib; Drug: Atezolizumab

Interventions

Cabozantinib DRUG

Oral once per day, Days 1 - 21 every 21 days

Also known as: Cabometyx

Cabozantinib and Atezolizumab

Atezolizumab DRUG

Intravenous (IV) once every 21 days

Also known as: Tecentriq

Cabozantinib and Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Males and females age ≥ 18 years
• ECOG Performance Status 0 - 1
• Pathologically confirmed advanced/metastatic NSCLC, with PD-L1\<1% based on IHC using 22C3 antibody
• At least one target lesion that can be assessed by RECIST 1.1
• For candidates who are not qualified for upfront FDA-approved targeted therapy, must be systemic treatment naïve (local palliative RT more than 4 weeks prior is allowed)
• For candidates who are qualified for upfront FDA-approved targeted therapy (e.g. having sensitizing mutations in EGFR, ALK and BRAF, etc.), treatment must have failed and received at least one line of ONLY FDA-approved targeted therapy
• Availability of a representative tumor specimen for correlative research. Optional but highly recommended: willing to undergo tumor tissue biopsy only if deemed safe and feasible by the investigator.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Women of childbearing potential must have a negative serum pregnancy test 72 hours prior to initiating treatment. Female participants are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site.
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use two forms of adequate contraception (hormonal AND barrier method of birth control) prior to study entry, for the duration of study participation and for 6 months following completion of therapy.
• Men of child-bearing potential must not father a child or donate sperm while on this study and for 6 months after the last study treatment.
• Adequate organ function
• Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count \>200/uL, and have an undetectable viral load. They must agree to continue on such anti-retroviral therapy per local standard treatment guideline
• Negative HBV and HCV tests at screening, with the following exception:

You may not qualify if:

• Simultaneously enrolled in any therapeutic clinical trial
• Current or anticipating use of other investigational agents while participating in this study
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment
• Patients harboring targetable mutations (e.g., EGFR, ALK and BRAF, etc.) who have not had at least one frontline targeted therapy fail, or have received other systemic therapies (e.g. chemotherapy, immunotherapy, etc.)
• Patients with carcinomatous meningitis (leptomeningeal metastasis)
• Undergone major surgery within 2 weeks prior to the start of study regimen, or has not achieved complete wound healing
• Presence of another cancer with disease manifestations or therapy that could adversely affect participant safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results. Otherwise, patients can be considered eligible, for example, locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• Prior treatment with cabozantinib and/or atezolizumab.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
• Radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Participants must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible participants must be neurologically asymptomatic and with corticosteroid no more than 10mg prednisone or equivalent at the time of first dose of study treatment.
• Concomitant anticoagulation with coumarin 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:

Sponsors & Collaborators

• Jun Zhang, MD, PhD: lead
• Exelixis: collaborator
• Genentech, Inc.: collaborator

Study Sites (4)

The University of Kansas Cancer Center - Westwood

Kansas City, Kansas, 66205, United States

Location

The University of Kansas Cancer Center - Indian Creek

Overland Park, Kansas, 66211, United States

Location

The University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

The University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

cabozantinib; atezolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Jun Zhang, MD, PhD

  University of Kansas Medical Center

  STUDY CHAIR

Central Study Contacts

Jonathon Barnette

CONTACT

913-588-5565; jbarnette@kumc.edu

Margana Whyte

CONTACT

913-945-6050; mwhyte@kumc.edu

Study Design

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

Study Record Dates

• First Submitted: February 18, 2023
• First Posted: May 15, 2023
• Study Start: December 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

US (4)