RECRUITING

A Pilot Phase II Study of Maintenance Cabozantinib Plus Pembrolizumab for Patients With Metastatic Squamous Non-Small Cell Lung Cancer (sqNSCLC)

Conditions

Metastatic Squamous Non-Small Cell Lung Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase II study to assess the efficacy, safety, and Health Related Quality of Life (HRQoL) of combination cabozantinib and pembrolizumab as maintenance therapy for patients with metastatic squamous Non Small Cell Lung Cancer(sqNSCLC) who have received 4 cycles of induction therapy with pembrolizumab, carboplatin, and nab-paclitaxel or paclitaxel.

Official Title

LUNG-IST-127: A Pilot Phase II Study of Maintenance Cabozantinib Plus Pembrolizumab (CP) for Patients With Metastatic sqNSCLC With Disease Control Following Induction Therapy

Quick Facts

Study Start:2022-12-28

Study Completion:2028-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05613413

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. 2. Age ≥ 18 years at the time of consent. 3. ECOG Performance Status of 0, 1, or 2 within 28 days prior to registration 4. Life expectancy of 6 months or greater as determined by the site investigator. 5. Subjects with histologically or cytologically confirmed squamous non-small cell lung cancer (sqNSCLC). 6. Subjects with stage IV NSCLC as defined by American Joint Committee on Cancer (AJCC) 8th Edition who have not received prior therapy for stage IV NSCLC. Patients with locally advanced or recurrent disease who are candidates for first-line induction systemic therapies for stage IV NSCLC are also allowed. 7. Subjects whose tumors have been tested for PD-L1 expression. 8. Demonstrate adequate organ function as defined below. All screening labs to be obtained within 14 days prior to registration. * Absolute Neutrophil Count (ANC): ≥ 1,500/uL without the support of Filgrastim or ≥ 1,000/L in subjects with constitutional neutropenia * Hemoglobin (Hgb): ≥ 9 g/dL * Platelets (Plt): ≥ 100,000/µL without transfusion. * Serum creatinine: ≤ 1.5 mg/dL * Calculated creatine clearance: ≥ 40 mL/min; for subjects with serum creatinine \> 1.5 mg/dL * Urine protein/creatinine ratio (UPCR): ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g * Total Bilirubin or Direct Bilirubin: ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease, ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN * Aspartate aminotransferase (AST): ≤ 3 × ULN or ≤ 5 x ULN for subjects with known hepatic metastasis * Alanine aminotransferase (ALT): ≤ 3 × ULN or ≤ 5 x ULN for subjects with known hepatic metastasis * Alkaline phosphatase (ALP): ≤ 3 × ULN or ≤ 5 x ULN with documented bone metastases. * Serum albumin: ≥ 2.8 g/dl * International Normalized Ratio (INR) : ≤ 1.3 × ULN; For subjects receiving warfarin or LMWH, the subjects must, in the site investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.3 × ULN if that is the goal of anticoagulant therapy. 9. Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. 10. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of cabozantinib and 4 months after the last dose of pembrolizumab. 11. Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. Female subjects of childbearing potential must not be pregnant at screening. Female subjects 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. 12. As determined by the enrolling physician or protocol designee, subjects should be capable of understanding and complying with the protocol requirements and must have signed the informed consent document. 13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.	1. Active infection requiring systemic therapy. 2. Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study. 3. Prior treatment with cabozantinib. 4. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment. 5. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment. 6. Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. 7. Radiologically documented evidence of major blood vessel invasion or encasement by cancer. 8. Radiographic evidence of central cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. Patients with peripheral cavitary lesions prior to induction therapy may be enrolled but will only be allowed to continue maintenance therapy on trial if they have disease control and resolution of cavitation after induction therapy. The development of cavitation recurrence or new intra-thoracic cavitations during maintenance therapy will require Cabozantinib to be stopped during maintenance therapy. 9. Patients with targetable genomic aberrations for which FDA-approved targeted therapy is available (e.g. ROS1, MET exon 14 skipping mutations, BRAFV600E, ALK, EGFR, ALK, RET, and NTRK fusions). 10. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: 1. Cardiovascular disorders: * iv. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation for at least 1 week before first dose of study treatment. 2. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: 3. Other clinically significant disorders that would preclude safe study participation. * vi. Any condition requiring systemic treatment with either steroid therapy (\>10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed. * a. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). * b. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.

Inclusion Criteria

Exclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent.
3. ECOG Performance Status of 0, 1, or 2 within 28 days prior to registration
4. Life expectancy of 6 months or greater as determined by the site investigator.
5. Subjects with histologically or cytologically confirmed squamous non-small cell lung cancer (sqNSCLC).
6. Subjects with stage IV NSCLC as defined by American Joint Committee on Cancer (AJCC) 8th Edition who have not received prior therapy for stage IV NSCLC. Patients with locally advanced or recurrent disease who are candidates for first-line induction systemic therapies for stage IV NSCLC are also allowed.
7. Subjects whose tumors have been tested for PD-L1 expression.
8. Demonstrate adequate organ function as defined below. All screening labs to be obtained within 14 days prior to registration.
* Absolute Neutrophil Count (ANC): ≥ 1,500/uL without the support of Filgrastim or ≥ 1,000/L in subjects with constitutional neutropenia
* Hemoglobin (Hgb): ≥ 9 g/dL
* Platelets (Plt): ≥ 100,000/µL without transfusion.
* Serum creatinine: ≤ 1.5 mg/dL
* Calculated creatine clearance: ≥ 40 mL/min; for subjects with serum creatinine \> 1.5 mg/dL
* Urine protein/creatinine ratio (UPCR): ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g
* Total Bilirubin or Direct Bilirubin: ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease, ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN
* Aspartate aminotransferase (AST): ≤ 3 × ULN or ≤ 5 x ULN for subjects with known hepatic metastasis
* Alanine aminotransferase (ALT): ≤ 3 × ULN or ≤ 5 x ULN for subjects with known hepatic metastasis
* Alkaline phosphatase (ALP): ≤ 3 × ULN or ≤ 5 x ULN with documented bone metastases.
* Serum albumin: ≥ 2.8 g/dl
* International Normalized Ratio (INR) : ≤ 1.3 × ULN; For subjects receiving warfarin or LMWH, the subjects must, in the site investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.3 × ULN if that is the goal of anticoagulant therapy.
9. Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
10. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of cabozantinib and 4 months after the last dose of pembrolizumab.
11. Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to registration. Female subjects of childbearing potential must not be pregnant at screening. Female subjects 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.
12. As determined by the enrolling physician or protocol designee, subjects should be capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

1. Active infection requiring systemic therapy.
2. Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
3. Prior treatment with cabozantinib.
4. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
5. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
6. Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
7. Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
8. Radiographic evidence of central cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. Patients with peripheral cavitary lesions prior to induction therapy may be enrolled but will only be allowed to continue maintenance therapy on trial if they have disease control and resolution of cavitation after induction therapy. The development of cavitation recurrence or new intra-thoracic cavitations during maintenance therapy will require Cabozantinib to be stopped during maintenance therapy.
9. Patients with targetable genomic aberrations for which FDA-approved targeted therapy is available (e.g. ROS1, MET exon 14 skipping mutations, BRAFV600E, ALK, EGFR, ALK, RET, and NTRK fusions).
10. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
1. Cardiovascular disorders:
* iv. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation for at least 1 week before first dose of study treatment.
2. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
3. Other clinically significant disorders that would preclude safe study participation.
* vi. Any condition requiring systemic treatment with either steroid therapy (\>10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed.
* a. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* b. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.

Contacts and Locations

Study Contact

Ryan Nguyen, DO

CONTACT

312-996-1581

rnguye8@uic.edu

Ruihong Yin, BSN

CONTACT

312-355-2545

ryin6@uic.edu

Study Locations (Sites)

Ryan Nguyen

Chicago, Illinois, 60612

United States

Collaborators and Investigators

Sponsor: University of Illinois at Chicago

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-12-28

Study Completion Date2028-09

Study Record Updates

Study Start Date2022-12-28

Study Completion Date2028-09

Terms related to this study

Additional Relevant MeSH Terms

Metastatic Squamous Non-Small Cell Lung Carcinoma