Certolizumab + Chemotherapy + Nivolumab for Lung Cancer

Recruiting at 7 trial locations

Overseen By Matthew Bott, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: TNF-α inhibitors, Immunosuppressants

Disqualifiers: Autoimmune disease, Active infection, Cardiovascular disease, 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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic immunosuppressive medications (like certain steroids) at least 2 weeks before starting the study treatment, unless they are low-dose or for specific conditions like COPD or asthma. If you're on other medications, the protocol doesn't specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination Certolizumab, Chemotherapy, and Nivolumab for lung cancer?

Research shows that combining chemotherapy with checkpoint inhibitors like pembrolizumab (similar to nivolumab) improves survival in non-small cell lung cancer. Additionally, pemetrexed and cisplatin, part of the chemotherapy regimen, are effective and well-tolerated in lung cancer treatment. ^{1 2 3 4 5}

Is the combination of Certolizumab, Chemotherapy, and Nivolumab safe for lung cancer patients?

Studies have shown that combinations of chemotherapy drugs like pemetrexed and carboplatin are generally safe for treating advanced lung cancer, even in elderly patients. These treatments are considered less toxic compared to other options, and safety data from similar drug combinations suggest they are tolerable for most patients. ^{2 6 7 8 9}

What makes the drug combination of Certolizumab, Chemotherapy, and Nivolumab unique for lung cancer treatment?

This drug combination is unique because it combines Certolizumab, an anti-inflammatory drug, with chemotherapy and Nivolumab, an immune checkpoint inhibitor, potentially offering a novel approach by targeting both inflammation and immune response in lung cancer treatment, which is different from the standard chemotherapy and immunotherapy combinations currently used. ^{3 4 10 11 12}

What is the purpose of this trial?

The purpose of the study is to explore adding the study drug certolizumab to standard chemotherapy as it may reduce the inflammation caused by the cancer and make the chemotherapy more effective in shrinking the cancer. This study will examine whether adding certolizumab to the usual treatment approach is better than, the same as, or worse than the usual approach alone.

Research Team

Paul Paik

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with stage II-III non-small cell lung cancer that can be surgically removed. They must have good performance status, proper organ function, no severe infections or allergies to the drugs used in the trial, and not be on immunosuppressive medication. Participants should not have other cancers or diseases that could affect results and must agree to use contraception.

Inclusion Criteria

My lung cancer is in stage II-III and can be surgically removed.

Your disease must be confirmed by a special test at MSKCC.

My bone marrow, liver, and kidneys are functioning well.

Exclusion Criteria

I am currently on medication for hepatitis B.

I am currently being treated for an infection, but it's not thrush.

You are allergic to Chinese hamster ovary cell products or any part of the nivolumab medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant platinum-based chemotherapy, nivolumab, and certolizumab

6-8 weeks

Surgery

Participants undergo surgical resection of lung cancer

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Treatment Details

Interventions

• Carboplatin
• Certolizumab
• Cisplatin
• Gemcitabine
• Nivolumab
• Pemetrexed

Trial Overview The study tests if adding Certolizumab to standard chemotherapy (Gemcitabine, Cisplatin, Pemetrexed, Carboplatin) plus Nivolumab improves treatment outcomes for lung cancer patients who are candidates for surgery. It aims to see if this combination reduces inflammation and makes chemo more effective at shrinking tumors.

Participant Groups

Group I: Participants with resectable stage II-III lung cancers (squamous cell carcinoma) Experimental Treatment 6 Interventions

This is a single arm phase II study of neoadjuvant platinum-based chemotherapy + nivolumab + certolizumab in participants with resectable stage II-III lung cancers. There will be separate adenocarcinoma and squamous cell carcinoma cohorts.

Group II: Participants with resectable stage II-III lung cancers (Adenocarcinoma) Experimental Treatment 6 Interventions

This is a single arm phase II study of neoadjuvant platinum-based chemotherapy + nivolumab + certolizumab in participants with resectable stage II-III lung cancers. There will be separate adenocarcinoma and squamous cell carcinoma cohorts.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In a study involving 1669 patients with non-small cell lung cancer (NSCLC), treatment with cisplatin and pemetrexed resulted in significantly longer survival without severe drug-related toxicity compared to cisplatin and gemcitabine, indicating a better clinical benefit-to-risk profile.

For patients with non-squamous NSCLC, cisplatin and pemetrexed not only improved survival without grade 3 or 4 toxicity but also showed superior outcomes in terms of survival without grade 4 toxicity, highlighting its effectiveness and tolerability in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaïve patients with advanced non-small cell lung cancer: a risk-benefit analysis of a large phase III study. Scagliotti, GV., Park, K., Patil, S., et al.[2022]

In a study of 53 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, treatment with pemetrexed plus cisplatin or carboplatin resulted in a median overall survival of 10 months and a median progression-free survival of 6 months.

The treatment was generally well-tolerated, with only a small percentage of patients experiencing severe side effects, such as grade 3 or 4 leukopenia and thrombocytopenia, indicating that pemetrexed combined with platinum-based drugs can be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. Zhang, GZ., Jiao, SC., Meng, ZT.[2021]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a study of 108 patients with advanced non-squamous non-small cell lung cancer (NSCLC), adding bevacizumab to pemetrexed as maintenance therapy significantly improved progression-free survival (PFS) compared to pemetrexed alone, with PFS of 7.0 months versus 5.4 months.

Patients who responded partially to initial treatment had a median overall survival of 29.6 months with the addition of bevacizumab, compared to 23.3 months with pemetrexed alone, suggesting a potential survival benefit from the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Phase II study of pemetrexed plus bevacizumab versus pemetrexed alone after treatment with cisplatin, pemetrexed, and bevacizumab in advanced non-squamous, non-small cell lung cancer: TORG (thoracic oncology research group) 1321. Kasai, T., Mori, K., Nakamura, Y., et al.[2023]

In a study of 109 patients with advanced non-squamous non-small cell lung cancer, the combination of pemetrexed and carboplatin followed by pemetrexed maintenance showed similar efficacy in elderly patients (≥70 years) compared to younger patients, with median progression-free survival of 5.2 months for the elderly versus 5.8 months for younger patients.

While elderly patients experienced more frequent grade 3/4 hematologic toxicities, these were manageable through dose adjustments, and non-hematologic toxicities were similar to those seen in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. Nogami, N., Nishio, M., Okamoto, I., et al.[2022]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

The study evaluated the safety and tolerability of carboplatin and pemetrexed in 20 elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, finding that the recommended dose was carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m², with manageable toxicities.

The treatment resulted in a 30% overall response rate, with a median progression-free survival of 4.8 months, indicating that this combination therapy is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer. Takeoka, H., Yamada, K., Azuma, K., et al.[2018]

The combination of pemetrexed, platinum, and pembrolizumab shows manageable toxicity, with most severe adverse events occurring early in treatment and resolving within two weeks, indicating a favorable safety profile for long-term use.

While there was a slightly higher incidence of renal toxicity in patients receiving the pembrolizumab combination compared to those on pemetrexed alone, this did not increase with longer treatment durations, supporting the regimen's safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. Garon, EB., Aerts, J., Kim, JS., et al.[2023]

In the EMPOWER-Lung 1 trial, cemiplimab significantly improved overall survival compared to platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression (≥50%).

Patients receiving cemiplimab reported better quality of life and functioning, with a lower risk of definitive deterioration in symptoms such as dyspnea, cough, and fatigue, indicating that cemiplimab not only extends survival but also enhances the patient's overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study. Gümüş, M., Chen, CI., Ivanescu, C., et al.[2023]

Immunotherapy, particularly with pembrolizumab or atezolizumab combined with platinum-based chemotherapy, has become an effective first-line treatment for advanced non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels.

Patients with negative PD-L1 expression and low tumor mutational burden (TMB) may not benefit from immunotherapy combinations and might be better treated with traditional platinum-based chemotherapy, highlighting the need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. Proto, C., Ferrara, R., Signorelli, D., et al.[2019]

Pemetrexed, a multitargeted antifolate agent, has shown comparable overall survival to docetaxel in second-line treatment for advanced non-small cell lung cancer (NSCLC), with a better toxicity profile, making it a safer option for patients.

In nonsquamous NSCLC, pemetrexed combined with folic acid and vitamin B12 significantly improved median survival to 9.3 months compared to 8.0 months with docetaxel, highlighting its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in second line of non-small cell lung cancer. Barata, F.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Survival without toxicity for cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemonaïve patients with advanced non-small cell lung cancer: a risk-benefit analysis of a large phase III study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pemetrexed plus cisplatin/carboplatin in previously treated locally advanced or metastatic non-small cell lung cancer patients. [2021]

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

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

4. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

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

Randomized, Phase II study of pemetrexed plus bevacizumab versus pemetrexed alone after treatment with cisplatin, pemetrexed, and bevacizumab in advanced non-squamous, non-small cell lung cancer: TORG (thoracic oncology research group) 1321. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. [2022]

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

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. [2022]

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

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer. [2018]

9. Ireland pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. [2023]

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

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. [2019]

12. Spain pubmed.ncbi.nlm.nih.gov

Pemetrexed in second line of non-small cell lung cancer. [2015]