Treatment Timing for Non-Small Cell Lung Cancer

Recruiting at 351 trial locations

Overseen By John M. Schallenkamp

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal timing for chemotherapy and immunotherapy in individuals with stage II-IIIB non-small cell lung cancer (NSCLC) that can be surgically removed. It compares the effects of administering treatments only after surgery versus both before and after surgery to determine which approach is more effective in treating the cancer. Participants will receive standard chemotherapy drugs like cisplatin and immunotherapies such as nivolumab. This trial may suit those with stage II-IIIB resectable NSCLC who have not recently undergone cancer treatments and do not have certain genetic mutations. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

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.

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

Research has shown that immune checkpoint inhibitors, such as atezolizumab, nivolumab, and pembrolizumab, have been tested for safety in people with non-small cell lung cancer (NSCLC). These treatments help the immune system attack cancer cells.

Studies have found that patients generally tolerate these drugs well. Common side effects include tiredness, skin rash, and diarrhea, but these are usually manageable. Serious side effects are less common and can include swelling in the lungs or liver.

One study monitored atezolizumab over five years and found it continued to be safe. Similarly, research on pembrolizumab over five years supported its safe use as a first treatment for NSCLC.

These findings provide reassurance about the safety of using these treatments in clinical trials for NSCLC. However, discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they involve using immune checkpoint inhibitors like atezolizumab, nivolumab, and pembrolizumab, which work by helping the immune system recognize and attack cancer cells more effectively. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, these drugs specifically target pathways that cancer cells use to evade the immune system. This approach has the potential to provide longer-lasting responses and improved overall survival rates. Additionally, the trial is exploring the timing of these treatments—whether given before or after surgery—which could optimize their effectiveness and offer more personalized treatment strategies.

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

This trial will compare different treatment timings for non-small cell lung cancer (NSCLC) using immune checkpoint inhibitors and chemotherapy. Studies have shown that immune checkpoint inhibitors, such as atezolizumab, nivolumab, and pembrolizumab, effectively treat NSCLC. These drugs help the immune system attack cancer cells and can improve survival rates. Research indicates that atezolizumab offers similar survival benefits to nivolumab and better results than some chemotherapy drugs like docetaxel. Nivolumab and pembrolizumab have also proven effective in real-world settings for patients with advanced NSCLC. These treatments enhance the body's ability to recognize and fight cancer cells. Participants in this trial may receive these immune checkpoint inhibitors as part of either neoadjuvant or adjuvant therapy, depending on their assigned treatment arm. ^{1 2 6 7 8}

Who Is on the Research Team?

Raid Aljumaily, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Daniel Morgensztern, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Linda Martin, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

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 do not have an active autoimmune disease, lung disease, or a transplant that would make immune therapy unsafe for me.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40552731/

Comparative Effectiveness of Atezolizumab, Nivolumab ... The study suggests no evidence of significant differences between the three IO drugs atezolizumab, nivolumab and pembrolizumab when used in second-line aNSCLC.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20557

Comparative real-world survival of first-line atezolizumab ... This study compared OS among older patients with mNSCLC who received first-line atezolizumab, nivolumab, or pembrolizumab.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1130634323005512

Effectiveness and safety of atezolizumab, nivolumab ... Abstract. Objective. To determine the effectiveness and safety of atezolizumab, nivolumab and pembrolizumab in patients with non-small cell lung cancer.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2786029

Comparative Effectiveness of Atezolizumab, Nivolumab ... This study found that atezolizumab was associated with superior OS compared with docetaxel and similar OS compared with nivolumab in a real-world cohort of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10453652/

Real-World Outcomes of Nivolumab, Pembrolizumab, and ... Real-World Outcomes of Nivolumab, Pembrolizumab, and Atezolizumab Treatment Efficacy in Korean Veterans with Stage IV Non-Small-Cell Lung Cancer.

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-24-01681

Five-Year Survival Outcomes With Atezolizumab After ... IMpower010 is the first study to report survival outcomes with a ≥5-year follow-up and continued to show benefit with atezolizumab versus BSC after adjuvant ...

7. lungcancerjournal.info lungcancerjournal.info/article/S0169-5002(25)00043-1/fulltext

Five-year efficacy and safety of pembrolizumab as first-line ... Five-year efficacy and safety of pembrolizumab as first-line treatment in patients with non-small cell lung cancer with PD-L1 tumor proportion score ≥50 %

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pds.70181

Comparative Effectiveness of Atezolizumab, Nivolumab ... This study compared the effectiveness of three immunotherapy (IO) drugs—atezolizumab, nivolumab and pembrolizumab—in treating advanced non–small ...