Cabozantinib + Pembrolizumab for Lung Cancer

(LUNG-IST-127 Trial)

Recruiting at 1 trial location

Overseen By Ryan Nguyen

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{1 4 6 7 8}

How 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. ^{1 4 5 9 10}

Eligibility 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.

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.

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

Treatment Details

Interventions

• Cabozantinib
• Pembrolizumab

Trial Overview 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.

Participant Groups

Group I: Single Experimental Treatment 3 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.

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a small study of three patients with IIIA squamous non-small-cell lung cancer, neoadjuvant treatment with camrelizumab combined with chemotherapy led to a reduction in tumor size and did not delay planned surgeries, indicating a favorable safety profile.

Two out of the three patients achieved a major pathological response, including one complete tumor regression, suggesting that camrelizumab may enhance the immune response against the tumor, as indicated by increased CD8+ T cells and PD-L1 expression in those patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant camrelizumab and chemotherapy in patients with resectable stage IIIA squamous non-small-cell lung cancer: Clinical experience of three cases. Li, X., Xia, C., Liu, M., et al.[2022]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Camrelizumab combined with carboplatin and pemetrexed chemotherapy showed promising efficacy in treating advanced lung adenocarcinoma, with an objective response rate of 58.8% and a disease control rate of 78.4% among 51 patients over a median follow-up of 14.9 months.

The treatment was generally well-tolerated, with most adverse events being mild to moderate (grade 1-2), including peripheral neuropathy and neutropenia, indicating that camrelizumab is a safe option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and prognostic factors of camrelizumab plus carboplatin and pemetrexed chemotherapy in advanced lung adenocarcinoma patients. Lv, J., Zhang, W., Deng, R., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Neoadjuvant camrelizumab and chemotherapy in patients with resectable stage IIIA squamous non-small-cell lung cancer: Clinical experience of three cases. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety and prognostic factors of camrelizumab plus carboplatin and pemetrexed chemotherapy in advanced lung adenocarcinoma patients. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]