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

NCT05613413 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2022-0875
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Squamous Non-Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (1)

• To estimate the median progression-free survival (PFS) of individuals with metastatic squamous non-small cell lung cancer (sqNSCLC)

  To estimate the median progression-free survival (PFS) of metastatic squamous non-small cell lung cancer (sqNSCLC) treated with maintenance cabozantinib in combination with pembrolizumab with disease control (defined as complete response, partial response, or stable disease) following standard first-line induction therapy with chemotherapy with pembrolizumab.

  Up to 24 months post-Cycle 1 Day 1 of induction (1 cycle = 21 days)

Secondary Outcomes (7)

• Adverse events as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5

  Up to 24 months post-Cycle 1 Day 1 of induction (1 cycle = 21 days)

• Estimate 6 month progression free survival (PFS) using RECIST v1.1 in subjects with disease control following standard first-line induction therapy who received cabozantinib in combination with pembrolizumab as maintenance therapy

  Up to 6 months post-Cycle 1 Day 1 of maintenance (1 cycle = 21 days)

• Estimate 12 month progression free survival (PFS) using RECIST v1.1 in subjects with disease control following standard first-line induction therapy who received cabozantinib in combination with pembrolizumab as maintenance therapy

  Up to 6 months post-Cycle 1 Day 1 of maintenance (1 cycle = 21 days)

• Estimate median 12 months overall survival (OS) using RECIST v1.1 in subjects with disease control following standard first-line induction therapy who received cabozantinib in combination with pembrolizumab as maintenance therapy

  Up to 12 months post-Cycle 1 Day 1 of maintenance (1 cycle = 21 days)

• Estimate 6 month overall response rate (ORR) using RECIST v1.1 in subjects with disease control following standard first-line induction therapy who received cabozantinib in combination with pembrolizumab as maintenance therapy

  Up to 6 months post-Cycle 1 Day 1 of maintenance (1 cycle = 21 days)

Study Arms (1)

Single

EXPERIMENTAL

All individuals will receive four cycles of induction therapy consisting of a combination of either carboplatin or cisplatin, nab-paclitaxel or paclitaxel, and pembrolizumab. Individuals' whose disease is stable or has decreased in size will proceed with maintenance therapy which will consist of pembrolizumab and cabozantinib.

Drug: Pacliltaxel or Nab-paclitaxel; Drug: Carboplatin or Cisplatin; Drug: Pembrolizumab; Drug: Cabozantinib

Interventions

Pacliltaxel or Nab-paclitaxel DRUG

Individuals will receive either paclitaxel or nab-paclitaxel as part of their induction treatment. Paclitaxel will be administered as a 200 mg/m2 IV infusion on Day 1 of Cycles 1-4 (1 cycle = 21 days). Nab-paclitaxel will be administered as a 100 mg/m2 IV infusion on Days 1, 8, and 15 of Cycles 1-4 (1 cycles = 21 days)

Single

Pembrolizumab DRUG

For the induction phase, pembrolizumab will be given as a 200 mg IV infusion on Day 1 of Cycles 1-4 of Induction (1 cycle = 21 days). For the maintenance phase, pembrolizumab will be given as a 200 mg IV infusion on Day 1 of each cycle (1 cycle = 21 days).

Single

Carboplatin or Cisplatin DRUG

Individuals will receive either paclitaxel or nab-paclitaxel as part of their induction treatment. Carboplatin will be administered as an AUC6 IV infusion on Day 1 of Cycles 1-4 (1 cycle = 21 days). Cisplatin will be administered as a 75 mg/m2 IV infusion on Day 1 of Cycles 1-4 (1 cycle = 21 days).

Single

Cabozantinib DRUG

For the maintenance phase, cabozantinib will be given at 40 mg orally each day for Days 1-21 of each cycle of maintenance (1 cycle = 21 days)

Single

Eligibility Criteria

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

You may qualify if:

• 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.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0, 1, or 2 within 28 days prior to registration
• Life expectancy of 6 months or greater as determined by the site investigator.
• Subjects with histologically or cytologically confirmed squamous non-small cell lung cancer (sqNSCLC).
• 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.
• Only patients with disease control, defined as complete response (CR), partial response (PR), or stable disease (SD) to induction therapy will be allowed to receive maintenance cabozantinib plus pembrolizumab arm of trial. Patients who have progression of disease (POD) following induction therapy will proceed to second-line therapy of local clinician's choice. Only those patients who proceed to maintenance cabozantinib and pembrolizumab therapy will be evaluable for primary and secondary objectives.
• Subjects whose tumors have been tested for PD-L1 expression.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 14 days prior to registration.
• \- White blood cell (WBC): ≥ 2.5K/uL
• 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

You may not qualify if:

• Active infection requiring systemic therapy.
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
• Prior treatment with cabozantinib.
• 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 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.
• Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
• 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.
• 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).
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• \- i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• \- ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• \- iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
• 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

Ryan Nguyen

Chicago, Illinois, 60612, United States

RECRUITING

MeSH Terms

Interventions

130-nm albumin-bound paclitaxel; Carboplatin; Cisplatin; pembrolizumab; cabozantinib

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Ryan Nguyen, DO

CONTACT

312-996-1581; rnguye8@uic.edu

Ruihong Yin, BSN

CONTACT

312-355-2545; ryin6@uic.edu

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: Principal Investigator

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: November 14, 2022
• Study Start: December 28, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

US (1)