Treatment Timing for Non-Small Cell Lung Cancer

Recruiting at 226 trial locations

Overseen By Kathryn Kelley, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Disqualifiers: Egfr, Alk alterations, Autoimmune, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 2

1100 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares standard therapy given after surgery (adjuvant) to standard therapy given before and after surgery (perioperative) in treating patients with stage II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable). The usual approach for patients with resectable NSCLC is chemotherapy and/or immunotherapy before surgery, after surgery, or both before and after surgery. This study is being done to find out which approach is better at treating patients with lung cancer. Treatment will be administered according to the current standard of care at the time of enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating physician. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Other chemotherapy drugs, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading . Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and immunotherapy prior to surgery and continuing treatment after surgery may be a more effective treatment option than adjuvant therapy alone in patients with stage II-IIIB resectable NSCLC.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer based on your specific situation.

What data supports the effectiveness of the drugs Atezolizumab, Nivolumab, and Pembrolizumab for treating non-small cell lung cancer?

Research shows that the drugs atezolizumab, nivolumab, and pembrolizumab, which are types of immunotherapy, have been effective in treating advanced non-small cell lung cancer, helping patients live longer and improving their overall outcomes. ^{1 2 3 4 5}

What safety data exists for treatments like Atezolizumab, Nivolumab, and Pembrolizumab in humans?

Atezolizumab, Nivolumab, and Pembrolizumab have been studied for safety in patients with non-small cell lung cancer, showing they are generally safe but can cause immune-related side effects. These treatments are approved for use because they improve survival and quality of life compared to standard chemotherapy. ^{4 5 6 7 8}

How is the drug treatment with Atezolizumab, Nivolumab, and Pembrolizumab different for non-small cell lung cancer?

This drug treatment is unique because it uses immunotherapy, which helps the body's immune system fight cancer by targeting specific proteins (PD-1/PD-L1) on cancer cells, potentially leading to longer-term survival compared to traditional chemotherapy. ^{3 5 9 10 11}

Research Team

Daniel Morgensztern, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Raid Aljumaily, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

This trial is for adults over 18 with stage II-IIIB resectable non-small cell lung cancer (NSCLC), who haven't had systemic treatment for NSCLC in the last 5 years. They should have a performance status indicating they can care for themselves and are up to light work. People with certain other cancers or treatments within the past 3 years, active autoimmune diseases, interstitial lung disease, transplants that conflict with immunotherapy, or untreated HIV are excluded.

Inclusion Criteria

My lung cancer is at stage IIA to IIIB and can be removed with surgery.

I haven't had systemic treatment for NSCLC in the last 5 years, except for early-stage cancer treated to cure.

I am 18 years old or older.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Neoadjuvant Therapy

Patients receive platinum-based doublet chemotherapy and immune checkpoint inhibitor therapy before surgery

Up to 4 cycles

Multiple visits for chemotherapy administration

Surgery

Patients undergo surgery to remove the tumor

Within 28 days of registration

1 visit (in-person)

Adjuvant Therapy

Patients receive immune checkpoint inhibitor therapy for up to 1 year after surgery

Up to 1 year

Regular visits for therapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months for up to 10 years

Biannual visits (in-person)

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Cisplatin
• Docetaxel
• Gemcitabine
• Nivolumab
• Pembrolizumab
• Pemetrexed
• Vinorelbine

Trial Overview The study compares standard post-surgery therapy to therapy given both before and after surgery in patients with resectable NSCLC. It includes chemotherapy drugs like cisplatin and docetaxel, which kill or stop tumor growth; pemetrexed and gemcitabine that block DNA creation; vinorelbine that prevents cells from spreading; plus immunotherapies like nivolumab, pembrolizumab, atezolizumab which boost the immune system's attack on tumors.

Participant Groups

Group I: Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy) Experimental Treatment 13 Interventions

NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor (nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines. SURGERY: Patients undergo surgery. ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.

Group II: Arm 1 (surgery, adjuvant therapy) Experimental Treatment 13 Interventions

SURGERY: Patients undergo surgery within 28 days of registration. ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease progression or unacceptable toxicity according to current approved guidelines. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A network meta-analysis of five trials showed that PD-1 inhibitors (pembrolizumab and nivolumab) had higher overall response rates (ORR) compared to the PD-L1 inhibitor (atezolizumab), particularly in patients with high PD-L1 expression.

Both pembrolizumab and nivolumab demonstrated superior overall survival (OS) benefits in various patient subgroups, but treatment decisions should also consider individual patient characteristics and safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. Almutairi, AR., Alkhatib, N., Martin, J., et al.[2019]

A meta-analysis of three randomized controlled trials involving 1,887 patients found that nivolumab and pembrolizumab have similar efficacy in treating advanced non-small-cell lung cancer, with no significant differences in overall response rates, overall survival, or progression-free survival.

However, pembrolizumab was associated with a higher incidence of severe adverse effects (grades ≥3) compared to nivolumab, indicating a potential safety concern when choosing between these two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials. Peng, TR., Tsai, FP., Wu, TW.[2018]

A systematic review of 28 studies involving second-line treatments for non-small-cell lung cancer (NSCLC) showed that PD-L1/PD-1 inhibitors (atezolizumab, nivolumab, and pembrolizumab) have comparable and superior expected 5-year overall survival rates compared to other treatment options.

In adjusted analyses, atezolizumab was ranked as the most effective PD-L1/PD-1 inhibitor for long-term survival, followed by nivolumab and pembrolizumab, highlighting the importance of these immunotherapies in improving outcomes for patients with NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies. Schulz, C., Gandara, D., Berardo, CG., et al.[2020]

In a study of 43 patients with non-small cell lung cancer, nivolumab showed the highest median progression-free survival (12.6 months) and overall survival (13.4 months), particularly in patients with fewer metastases and better performance status.

While 85% of patients experienced some adverse effects, the development of vitiligo in patients treated with nivolumab was associated with a more durable response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer. Burgos-San José, A., Colomer-Aguilar, C., Martínez-Caballero, D., et al.[2021]

Anti-PD-1/PD-L1 therapies (atezolizumab, pembrolizumab, nivolumab) significantly improve overall survival and progression-free survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC) compared to docetaxel, based on a review of 14 trials involving 3786 subjects.

For patients with EGFR wild-type NSCLC, anti-PD-1/PD-L1 therapy offers better survival outcomes than EGFR-TKIs, while for EGFR mutant patients, it is less effective than EGFR-TKIs in terms of progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. Sheng, Z., Zhu, X., Sun, Y., et al.[2021]

In a study of 271 advanced non-small-cell lung cancer patients treated with PD-1 antibodies, 42.8% experienced immune-related adverse events (irAEs), which were linked to lower overall survival (OS) rates, particularly in those with severe irAEs like colitis.

Patients who required treatment interruption due to irAEs had significantly lower OS compared to those who continued therapy, highlighting the need for better management strategies for irAEs to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis. Ksienski, D., Wai, ES., Croteau, N., et al.[2019]

Immune checkpoint inhibitors like nivolumab, pembrolizumab, and atezolizumab have been shown to improve response rates, overall survival, and quality of life in patients with advanced non-small cell lung cancer (NSCLC) compared to standard chemotherapy.

The use of these agents presents clinical challenges, including managing rare immune-related adverse events and determining optimal treatment duration and patient selection, which are crucial for effective real-world application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade for advanced non-small cell lung cancer: challenging clinical scenarios. Tay, R., Prelaj, A., Califano, R.[2023]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

In a study of 18 advanced non-small cell lung cancer patients, re-treatment with the anti-PD-L1 antibody atezolizumab after anti-PD-1 therapy showed limited efficacy, with a median progression-free survival of only 2.9 months and no patients achieving a partial or complete response.

The safety profile of atezolizumab was comparable to that of the previous anti-PD-1 treatments, as there were no significant differences in immune-related adverse events between the two therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment With Anti-PD-L1 Antibody in Advanced Non-small Cell Lung Cancer Previously Treated With Anti-PD-1 Antibodies. Fujita, K., Uchida, N., Yamamoto, Y., et al.[2019]

In a study of 1519 cancer patients, the clearance (CL) of the PD-L1 inhibitor atezolizumab was primarily influenced by factors such as body weight, albumin levels, tumor size, and gender, but these factors did not necessitate changes in dosing recommendations.

The best-fitting model indicated that as patients' albumin levels improved, the clearance of atezolizumab decreased, suggesting that the drug's effectiveness may be linked to the patient's overall health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-dependent population PK models of single-agent atezolizumab in patients with cancer. Marchand, M., Zhang, R., Chan, P., et al.[2021]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials. [2018]

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

Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies. [2020]

4. Spain pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in metastatic non-small cell lung cancer. [2021]

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

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. [2021]

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

Efficacy of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer Needing Treatment Interruption Because of Adverse Events: A Retrospective Multicenter Analysis. [2019]

7. China pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade for advanced non-small cell lung cancer: challenging clinical scenarios. [2023]

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

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Retreatment With Anti-PD-L1 Antibody in Advanced Non-small Cell Lung Cancer Previously Treated With Anti-PD-1 Antibodies. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Time-dependent population PK models of single-agent atezolizumab in patients with cancer. [2021]

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

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2023]