Atezolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Not currently recruiting at 230 trial locations

Overseen By Reference Study ID Number: GO40241 www.roche.com/about_roche/roche_worldwide.htm

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: CD137 agonists, Anti-PD-1, Anti-PD-L1

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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

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: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment option for people with non-small cell lung cancer (NSCLC) that can be surgically removed. The researchers aim to determine if adding atezolizumab, an immune-boosting drug, to standard chemotherapy before surgery can enhance cancer treatment. Participants are randomly assigned to receive either atezolizumab with chemotherapy or a placebo with chemotherapy before surgery, followed by further treatment or supportive care after surgery. Eligible participants have NSCLC that can be surgically removed and have not received previous lung cancer treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

A previous study found that the combination of atezolizumab and chemotherapy was well-tolerated by patients. The study showed that the side effects of this combination were manageable, allowing most patients to continue treatment without interruption.

Research indicates that carboplatin is safe for treating non-small cell lung cancer. It is commonly used, and doctors are familiar with its side effects.

Cisplatin also has a good safety record in lung cancer treatment. Studies show it can cause side effects, but doctors generally know how to manage them.

Gemcitabine has proven to be well-tolerated. Its side effects are known, and it has been used for many years in lung cancer treatment.

Nab-paclitaxel, when used with platinum drugs, has a good safety profile. Most patients handle the treatment well, and the side effects are manageable.

Lastly, pemetrexed is known for causing fewer side effects. It is widely used for non-small cell lung cancer and is considered safe.

Overall, these medications have strong safety records for lung cancer treatment. They have been extensively studied, and their side effects are well-known and manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about atezolizumab for non-small cell lung cancer because it works differently than traditional chemotherapy. While most current treatments focus on directly killing cancer cells, atezolizumab is an immunotherapy that helps the body's immune system recognize and attack cancer cells. This is achieved by targeting the PD-L1 protein, which tumors often use to hide from the immune system. By combining atezolizumab with standard platinum-based chemotherapies, there's potential for a more powerful, comprehensive attack on the cancer, offering hope for improved outcomes.

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

In this trial, participants will receive either atezolizumab combined with platinum-based chemotherapy or a placebo combined with platinum-based chemotherapy. Previous studies have shown that atezolizumab holds promise for treating non-small cell lung cancer (NSCLC), helping patients with advanced stages live longer. When combined with chemotherapy, it further increased overall survival. Chemotherapy with drugs like carboplatin, cisplatin, gemcitabine, nab-paclitaxel, and pemetrexed has proven effective for NSCLC. Specifically, cisplatin-based chemotherapy improved survival in cases where the cancer could be surgically removed. Overall, combining atezolizumab with chemotherapy shows strong potential to effectively treat NSCLC. ^{3 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for people with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC). Participants must be able to undergo surgery, have not had prior lung cancer treatment, and should not have other cancers within the last 5 years. They need good heart and lung function, no serious infections recently, no history of certain autoimmune diseases or pneumonitis, and cannot be pregnant.

Inclusion Criteria

My lung cancer is confirmed and can be surgically removed. It's classified as Stage II, IIIA, or certain IIIB.

A thoracic surgeon has confirmed I can have surgery to remove all of my lung cancer.

You have a disease that can be measured according to specific guidelines.

Exclusion Criteria

My lung cancer is non-squamous with specific ALK and EGFR mutations.

I have a history of lung scarring or inflammation.

I have not had a severe infection in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 4 cycles of atezolizumab or placebo in combination with platinum-based chemotherapy

12 weeks

4 cycles (each cycle is 21 days)

Surgery

Participants undergo surgical resection of the tumor

At time of surgery

Adjuvant/Postoperative Treatment

Participants receive 16 cycles of atezolizumab or best supportive care

48 weeks

16 cycles (each cycle is 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 96 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab (MPDL3280A)
• Carboplatin
• Cisplatin
• Gemcitabine
• Nab-paclitaxel
• Pemetrexed
• Placebo Comparator

Trial Overview The study tests Atezolizumab (an anti-PD-L1 antibody) combined with chemotherapy before surgery compared to a placebo plus chemotherapy in patients with NSCLC. After surgery, participants will receive Atezolizumab or supportive care. The goal is to see if this improves outcomes.

How Is the Trial Designed?

Group I: Arm A: Atezolizumab + platinum-based chemotherapy Experimental Treatment 6 Interventions

Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab

Group II: Arm B: Placebo + platinum-based chemotherapy Placebo Group 6 Interventions

Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy Platinum-based chemotherapy may include: * carboplatin + pemetrexed * carboplatin + nab-paclitaxel * cisplatin + pemetrexed * cisplatin + gemcitabine Participants will receive best supportive care and monitoring after surgery

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., et al.[2023]

The ANTELOPE trial is a phase II study comparing the efficacy of a pemetrexed-free regimen (atezolizumab, carboplatin, and nab-paclitaxel) against a pemetrexed-based regimen (pembrolizumab, cis-/carboplatin, and pemetrexed) in treating TTF-1 negative non-small cell lung adenocarcinoma (NSCLC/ADC).

This trial aims to enroll 136 participants across 30 sites in Germany, focusing on overall survival as the primary endpoint, which will help determine the best treatment approach for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). Frost, N., Bleckmann, A., Griesinger, F., et al.[2023]

In a study involving 1187 patients with nonsquamous non-small-cell lung cancer, the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) showed a tolerable safety profile compared to other treatment regimens, with manageable adverse events during both induction and maintenance phases.

Patient-reported outcomes indicated that all treatment regimens, including ABCP, did not lead to significant declines in quality of life or physical functioning, suggesting that the addition of atezolizumab does not substantially increase the treatment burden for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell Lung Cancer. Reck, M., Wehler, T., Orlandi, F., et al.[2021]

In a study of 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

Atezolizumab, an anti-PD-L1 therapy, has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), particularly in patients who have already undergone other treatments.

Emerging evidence suggests that administering atezolizumab earlier, especially in combination with chemotherapy and bevacizumab, may enhance its effectiveness, highlighting the importance of patient selection based on clinical and immune-related factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives. Facchinetti, F., Bordi, P., Leonetti, A., et al.[2023]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

In a study of 245 treatment-naïve Chinese patients with stage IV non-squamous non-small-cell lung cancer, the addition of atezolizumab to carboplatin and nab-paclitaxel significantly improved progression-free survival (12.98 months vs. 10.89 months) and overall survival (38.04 months vs. 33.59 months) compared to chemotherapy alone.

However, this combination therapy also led to a higher incidence of grade ≥3 adverse events, with 84% of patients in the atezolizumab group experiencing severe side effects, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus carboplatin and nab-paclitaxel versus carboplatin and nab-paclitaxel as treatments for Chinese, treatment-naïve, stage IV, non-squamous, non-small-cell lung cancer patients: A retrospective analysis. Chen, Y., Kang, S., Yan, M.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9716834/

updated long-term efficacy of atezolizumab in a diverse ... In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39758245/

Outcomes of Combined Atezolizumab Plus Chemotherapy ... Immune-related adverse events were observed in 27.7% of patients, with grade 3 or higher in 9.9% of patients, and grade 5 in 2.1% of patients.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225000164

Effectiveness and safety of Atezolizumab in patients with ... The two-cohort non-interventional study HYPERION assessed the effectiveness and safety of atezolizumab in 353 patients with locally-advanced or metastatic ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1917346

Atezolizumab for First-Line Treatment of PD-L1–Selected ... Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression.

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.909027/full

Efficacy of Atezolizumab for Advanced Non-Small Cell ... The aims of this study are to clarify the potency of atezolizumab-based therapy in advanced NSCLC patients with different clinical and molecular features.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11696331/

Outcomes of Combined Atezolizumab Plus Chemotherapy in ... The objectives of this study were to confirm the treatment outcomes of combined atezolizumab plus chemotherapy, and to identify prognostic factors.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20007

Efficacy and safety analysis of adjuvant atezolizumab in ... Efficacy and safety analysis of adjuvant atezolizumab in non-small cell lung cancer patients in China: A single center retrospective analysis.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03922997

NCT03922997 | A Study to Investigate the Safety and ... This is a phase III, single-arm, multicenter study of the long-term safety and efficacy of atezolizumab treatment in patients with Stage IIIb or Stage IV non- ...

9. lungcancerjournal.info lungcancerjournal.info/article/S0169-5002(24)00377-5/fulltext

Safety and Patient-Reported outcomes of atezolizumab plus ... PPAB and PPA combinations seem tolerable and manageable in patients with stage IIIB/IV non-squamous NSCLC with oncogenic addiction (EGFR ...