Tocilizumab + Atezolizumab for Non-Small Cell Lung Cancer

Overseen By Melissa Volpe, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Must be taking: Checkpoint inhibitors

Disqualifiers: Brain metastases, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a research study to evaluate the safety and effectiveness of tocilizumab in combination with atezolizumab to treat non-small cell lung cancer.

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.

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

Atezolizumab has been shown to significantly improve overall survival in patients with advanced non-small cell lung cancer who have previously received chemotherapy, as demonstrated in the phase II POPLAR and phase III OAK trials. It also showed promising response rates in the phase II FIR and BIRCH trials, particularly in patients with high PD-L1 expression. ^{1 2 3 4 5}

Is the combination of Tocilizumab and Atezolizumab safe for humans?

Atezolizumab has been shown to have an acceptable safety profile in patients with non-small cell lung cancer, with common side effects including fatigue, decreased appetite, and nausea. Serious side effects like pneumonia and liver inflammation occurred in a small percentage of patients. Tocilizumab, used for other conditions, also has a known safety profile, but specific safety data for the combination of Tocilizumab and Atezolizumab is not provided in the available research. ^{2 3 6 7 8}

What makes the drug Atezolizumab unique for treating non-small cell lung cancer?

Atezolizumab is unique because it is an immune checkpoint inhibitor that targets PD-L1, helping the immune system attack cancer cells more effectively. It has shown improved survival rates compared to traditional chemotherapy in patients with advanced non-small cell lung cancer who have already undergone chemotherapy. ^{1 2 4 5 6}

Research Team

Melina Marmarelis, MD

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

Adults over 18 with advanced non-squamous Non-Small Cell Lung Cancer (Stage IV or recurrent) who've had at least one prior therapy and were treated with a checkpoint inhibitor right before joining. They should be relatively fit (ECOG PS 0-2). Those with autoimmune diseases, severe past immunotherapy side effects, certain genetic mutations, brain metastases, another active cancer, or uncontrolled cancer pain can't join.

Inclusion Criteria

I can take care of myself and perform daily activities.

I am 18 or older with advanced non-squamous NSCLC.

I have undergone at least one treatment for my condition.

Exclusion Criteria

My cancer has a mutation that can be treated with targeted therapy.

I have pain from my cancer that isn't relieved by treatment.

I haven't had severe side effects from previous immunotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atezolizumab 1200mg IV and Tocilizumab 6mg/kg IV (or Tocilizumab 4mg/kg IV) every 21 days

12 weeks

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Atezolizumab
• Tocilizumab

Trial Overview The trial is testing the combination of two drugs: Tocilizumab and Atezolizumab for treating lung cancer that hasn't responded to first-line immune therapies. It aims to assess how safe and effective this drug duo is in managing the disease.

Participant Groups

Group I: Atezolizumab and Tocilizumab Experimental Treatment 2 Interventions

Participants receive Atezolizumab 1200mg IV and Tocilizumab 6mg/kg IV (or Tocilizumab 4mg/kg IV) every 21 days

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

Atezolizumab, an immune checkpoint inhibitor, has been shown to significantly prolong overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy, based on results from the phase II POPLAR and phase III OAK trials.

The treatment is particularly effective in patients with higher PD-L1 expression, demonstrating higher objective response rates, and it has a manageable safety profile with a low incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. Blair, HA.[2020]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., 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]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, an immunotherapy targeting PD-L1, has shown promising efficacy in treating non-small-cell lung cancer (NSCLC), particularly in clinical trials like the phase II FIR and BIRCH studies, which evaluated its effectiveness based on PD-L1 expression.

In randomized trials (POPLAR and OAK), atezolizumab demonstrated improved efficacy compared to standard chemotherapy (docetaxel) in previously treated NSCLC patients, suggesting a favorable risk-benefit ratio for second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospects and progress of atezolizumab in non-small cell lung cancer. Vansteenkiste, J., Wauters, E., Park, K., et al.[2019]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab therapy significantly improves overall survival (median OS of 11.2 months) in patients with previously treated advanced non-small cell lung cancer (NSCLC), demonstrating its efficacy in a diverse patient population.

The treatment has a manageable safety profile, with serious adverse events occurring in only 8.0% of patients and no new safety signals identified, indicating it is a viable option for patients often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2022]

Atezolizumab monotherapy demonstrated a manageable safety profile in Chinese patients with previously treated advanced non-small cell lung cancer (NSCLC), with serious adverse events occurring in 25.7% of patients and immune-related adverse events in 47.5%.

The treatment showed clinically meaningful efficacy, with a median overall survival of 15.31 months and a 24-month overall survival rate of 37.4%, while specific gene mutations and the presence of CD8+ TILs were associated with better responses to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of atezolizumab in Chinese patients with previously treated locally advanced or metastatic non-small cell lung cancer: An open-label, single-arm, multicenter study. Xu, Y., Huang, Z., Chang, J., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

3. 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]

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

Atezolizumab: First Global Approval. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Prospects and progress of atezolizumab in non-small cell lung cancer. [2019]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Safety and efficacy of atezolizumab in Chinese patients with previously treated locally advanced or metastatic non-small cell lung cancer: An open-label, single-arm, multicenter study. [2023]