Atezolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 198 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

453 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Atezolizumab combined with chemotherapy for non-small cell lung cancer?

Research shows that Atezolizumab, when combined with chemotherapy, can enhance the immune system's ability to fight non-small cell lung cancer, leading to improved outcomes compared to chemotherapy alone. Studies have demonstrated its effectiveness in both previously treated and treatment-naïve patients, particularly those with PD-L1-positive tumors. ^{1 2 3 4 5}

Is the combination of Atezolizumab and chemotherapy safe for treating non-small cell lung cancer?

The combination of Atezolizumab with chemotherapy drugs like carboplatin and nab-paclitaxel has been studied for safety in treating non-small cell lung cancer. While it can improve survival, it may also increase the risk of severe side effects (grade ≥3 adverse events), such as fatigue, nausea, and low blood cell counts. ^{1 3 6 7 8}

What makes the drug combination of Atezolizumab and chemotherapy unique for treating non-small cell lung cancer?

This treatment is unique because it combines Atezolizumab, an immunotherapy drug that boosts the immune system's ability to fight cancer, with traditional chemotherapy, which directly kills cancer cells. This combination aims to enhance the overall effectiveness of treatment by using both the body's immune response and direct cancer cell attack. ^{1 2 4 9 10}

What is the purpose of this trial?

This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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, 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, 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]

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 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]

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]

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]

References

1. England 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. [2022]

2. England 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. [2022]

3. Germany 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives. [2023]

6. United States 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). [2023]

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

Atezolizumab in Japanese Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer: A Subgroup Analysis of the Phase 3 OAK Study. [2022]

8. United States 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. [2022]

9. United States 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. [2021]

10. Switzerland 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. [2023]