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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a drug called certolizumab to standard chemotherapy can reduce inflammation and enhance treatment effectiveness for lung cancer. The study targets individuals with stage II-III non-small cell lung cancer, specifically adenocarcinoma or squamous cell carcinoma, that can be surgically removed. Participants must have a confirmed diagnosis of this cancer type, and their cancer must remain untreated. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that certolizumab, when combined with chemotherapy and nivolumab, is well-tolerated by people with lung cancer and other solid tumors. Studies have found that adding certolizumab, which reduces inflammation, does not raise additional safety concerns. Chemotherapy drugs like pemetrexed and carboplatin are generally safe for treating advanced lung cancer, even in older adults. Nivolumab, a type of immunotherapy, has been used safely in lung cancer and is FDA-approved for other conditions, indicating it is generally well-tolerated. Overall, this combination of treatments has not shown major safety issues in studies, which is promising for its use in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Certolizumab in combination with chemotherapy and Nivolumab for lung cancer because it adds a novel approach to enhancing the immune system's ability to fight cancer. Unlike standard treatments like chemotherapy alone or in combination with PD-1 inhibitors like Nivolumab, Certolizumab targets and inhibits TNF-alpha, a protein involved in inflammation that can promote cancer growth. This combination aims to boost the immune response against cancer cells more effectively than traditional therapies, potentially leading to better outcomes for patients with resectable stage II-III lung cancers.

What evidence suggests that this trial's treatments could be effective for lung cancer?

This trial will evaluate the combination of certolizumab, chemotherapy, and nivolumab for treating resectable stage II-III lung cancers. Studies have shown that adding certolizumab to chemotherapy and nivolumab may enhance lung cancer treatment. Certolizumab reduces inflammation, potentially improving chemotherapy's ability to shrink tumors. Nivolumab, a medicine that aids the immune system in fighting cancer, has improved survival rates when combined with chemotherapy for non-small cell lung cancer. Previous research suggests that certolizumab can also help prevent cancer from spreading. Together, these treatments could be more effective against lung cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Paul Paik

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Treatment with investigational therapy within 28 days prior to initiation of study treatment

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04991025

Adding Certolizumab to Chemotherapy + Nivolumab in ... 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12185780/

Immune Checkpoint Inhibitor‐Based Therapy as the First‐Line ... Immune checkpoint inhibitor‐based first‐line therapy improves survival in advanced NSCLC, yet its efficacy is moderated by PD‐L1 expression and genomic ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-09613

Nivolumab + Platinum-based Chemotherapy ... This phase II trial tests how well certolizumab pegol in addition to chemotherapy cisplatin and nivolumab works in treating stage II-III non-small cell lung ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9568581/

Phase I trial of the TNF-α inhibitor certolizumab plus ... In this work, we validate the anti-metastatic effect of certolizumab in a preclinical model of lung cancer and demonstrate tolerability and ...

5. withpower.com withpower.com/trial/phase-3-lung-neoplasms-9-2021-46226

Certolizumab + Chemotherapy + 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.

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/1759-7714.70113

Immune Checkpoint Inhibitor‐Based Therapy as the First‐ ... Immune checkpoint inhibitor-based first-line therapy improves survival in advanced NSCLC, yet its efficacy is moderated by PD-L1 expression ...