Cabozantinib + Pembrolizumab for Lung Cancer
(LUNG-IST-127 Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Illinois at Chicago
Must be taking: Pembrolizumab, Carboplatin, Paclitaxel
Must not be taking: Anticoagulants, Steroids, Kinase inhibitors
Disqualifiers: Infection, Hypertension, Autoimmune, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received certain cancer treatments or radiation therapy shortly before starting the trial, and some medications like specific anticoagulants are not allowed. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug combination of Cabozantinib and Pembrolizumab for lung cancer?
Pembrolizumab, one of the drugs in the combination, has shown promising results in treating non-small cell lung cancer (NSCLC) by helping the immune system fight cancer cells. It is approved for use in certain types of lung cancer and has been effective in reducing tumor size and improving patient outcomes.
12345Is the combination of Cabozantinib and Pembrolizumab generally safe for humans?
Pembrolizumab (Keytruda) has been used in various cancer treatments and is generally considered less toxic than traditional chemotherapy, but it can cause side effects like pneumonitis (lung inflammation) in 1%-5% of patients. Safety data for Cabozantinib in combination with Pembrolizumab specifically for lung cancer is not detailed here, but Pembrolizumab alone has been approved for several cancers, indicating a recognized safety profile.
14678How is the drug combination of Cabozantinib and Pembrolizumab unique for lung cancer treatment?
The combination of Cabozantinib and Pembrolizumab is unique because it pairs a PD-1 inhibitor (Pembrolizumab) with a multi-targeted tyrosine kinase inhibitor (Cabozantinib), potentially enhancing the immune response against lung cancer cells. This approach is different from standard treatments that typically use chemotherapy or single-agent immunotherapy.
145910Eligibility Criteria
Adults with metastatic squamous Non-Small Cell Lung Cancer who've had prior treatment without disease progression. They must be in good health otherwise, understand the study and consent to it, use contraception, and have no other active cancers or severe allergies to trial drugs.Inclusion Criteria
My recent tests show my organs are functioning well.
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
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.
+11 more
Exclusion Criteria
I haven't had radiation for bone metastasis in the last 2 weeks or any radiation in the last 4 weeks.
I haven't taken any kinase inhibitor medication in the last 2 weeks.
I haven't had any cancer treatment in the last 4 weeks.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction Therapy
Participants receive 4 cycles of induction therapy with pembrolizumab, carboplatin, and nab-paclitaxel or paclitaxel
12 weeks
Maintenance Therapy
Participants receive maintenance therapy with cabozantinib and pembrolizumab following disease control
19 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 months
Participant Groups
The effectiveness of Cabozantinib combined with Pembrolizumab as a maintenance therapy for lung cancer patients post-induction therapy is being tested. The goal is to see how well these drugs work together after initial chemotherapy.
1Treatment groups
Experimental Treatment
Group I: SingleExperimental Treatment3 Interventions
All subjects will receive carbozantinib 40mg PO once daily Days 1-21 Q3W and pembrolizumab 200mg IV infusion Q3W or 400mg IV infusion Q6W per the treating physician's discretion as maintenance therapy following 4 cycles of induction therapy with disease control
Note: Cabozantinib should be stopped at least 3 weeks prior to elective surgery. Do not administer cabozantinib for at least 2 weeks after major surgery and until complete wound healing.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Illinois at ChicagoChicago, IL
Ryan NguyenChicago, IL
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Who Is Running the Clinical Trial?
University of Illinois at ChicagoLead Sponsor
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Neoadjuvant camrelizumab and chemotherapy in patients with resectable stage IIIA squamous non-small-cell lung cancer: Clinical experience of three cases. [2022]Neoadjuvant immunochemotherapy has attracted much attention as a treatment for locally advanced non-small-cell lung cancer. However, there is scarce evidence of the safety and efficacy of camrelizumab as neoadjuvant in lung cancer. Here, we present three patients who were diagnosed with IIIA squamous non-small-cell lung cancer from September to December in 2020 and received two cycles of neoadjuvant camrelizumab plus nab-paclitaxel and nedaplatin, followed by surgical resection. All three patients had a reduction in the tumor size on CT image and not delayed planned surgery. We did not observe grade 3 or 4 adverse events. Two of the three patients achieved a major pathological response (MPR), including one complete tumor regression of the primary lung tumor. Multiplex fluorescent immunohistochemistry revealed that CD8+ T cells, FoxP3+ regulatory T cells, and PD-L1 expression on immune cells in the surgical specimen were much higher than in the pretreatment biopsy sample in patients with MPR. This was not observed in the patient without MPR. Camrelizumab plus chemotherapy could potentially be a neoadjuvant regimen for resectable IIIA squamous non-small-cell lung cancer, with a high MPR proportion, and did not compromise surgical procedure. Our findings should be validated in a future randomized clinical trial.
[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Efficacy, safety and prognostic factors of camrelizumab plus carboplatin and pemetrexed chemotherapy in advanced lung adenocarcinoma patients. [2022]Camrelizumab is a recently developed PD-1 inhibitor in China applied in treating different cancers including lung cancer. This study is designed to evaluate the efficacy, safety and prognostic factors for camrelizumab plus carboplatin and pemetrexed (CP) chemotherapy in treating patients with advanced lung adenocarcinoma.
Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]Pembrolizumab is a highly selective IgG4 kappa isotype monoclonal antibody against the programmed cell death-1 (PD-1) molecule. In the treatment of non-small cell lung cancer (NSCLC), pembrolizumab has demonstrated significant efficacy, significant survival outcomes, long-lasting responses, and a good safety profile compared with cytotoxic chemotherapy.