Atezolizumab + Chemotherapy for Small Cell Lung Cancer

(SKYSCRAPER-02 Trial)

Recruiting at 202 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunostimulatory agents

Disqualifiers: CNS metastases, Autoimmune disease, HIV, others

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: 4

490 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), LDH (\</= upper limit of normal \[ULN\] vs. \> ULN), and presence or history of brain metastasis (yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment regimens during induction phase: * Arm A: Tiragolumab plus atezolizumab plus CE * Arm B: Placebo plus atezolizumab plus CE Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had any prior systemic treatment for small cell lung cancer or certain investigational or immunostimulatory agents recently. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Atezolizumab, Tecentriq, Carboplatin, Paraplatin, Carboplatinum, Etoposide, Eposin, VP-16, Vepesid, Tiragolumab for treating small cell lung cancer?

Research shows that adding atezolizumab to chemotherapy significantly improves survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone, making it a valuable first-line treatment option. ^{1 2 3 4 5}

Is the combination of Atezolizumab, Carboplatin, and Etoposide safe for treating small cell lung cancer?

The combination of Atezolizumab, Carboplatin, and Etoposide for small cell lung cancer is generally well tolerated, with no new safety concerns beyond those known for each drug individually. Common side effects include blood-related issues, skin rash, and low thyroid function, but it does not negatively affect patients' quality of life. ^{2 3 6 7 8}

What makes the drug combination of Atezolizumab, Carboplatin, Etoposide, and Tiragolumab unique for treating small cell lung cancer?

This treatment is unique because it combines atezolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with traditional chemotherapy drugs carboplatin and etoposide, and adds tiragolumab, which may further enhance the immune response. This combination aims to improve survival outcomes in patients with extensive-stage small cell lung cancer. ^{1 2 3 6 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with untreated extensive-stage small cell lung cancer (ES-SCLC). Participants should have no prior treatments, good organ function, and an ECOG Performance Status of 0 or 1. They can't join if they have autoimmune diseases, active CNS metastases, previous immune therapy use, recent immunostimulatory agents use, other cancers within the last 5 years (except those with low risk), HIV/Hepatitis B/C infections, severe infections at randomization time or a history of certain lung conditions.

Inclusion Criteria

My lung cancer is confirmed to be extensive-stage small cell.

My blood and organs are functioning well.

I haven't had chemo or radiotherapy for my small cell lung cancer in the last 6 months.

Exclusion Criteria

I do not have a severe infection currently.

I have previously received treatments targeting the immune system.

I have had lung conditions like pulmonary fibrosis or pneumonitis, or my CT scan shows active pneumonitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive either tiragolumab plus atezolizumab plus carboplatin and etoposide (CE) or placebo plus atezolizumab plus CE for 4 cycles

12 weeks

4 visits (in-person) per cycle

Maintenance Therapy

Participants continue maintenance therapy with either atezolizumab plus tiragolumab or atezolizumab plus placebo

Ongoing until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 50 months

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• Tiragolumab

Trial Overview The study tests whether adding Tiragolumab to Atezolizumab plus chemotherapy (Carboplatin and Etoposide) improves outcomes compared to using a placebo with Atezolizumab and the same chemo in ES-SCLC patients. After initial treatment phase ('induction'), participants continue maintenance therapy either with both drugs or one drug plus placebo.

Participant Groups

Group I: Tiragolumab + Atezolizumab + CE Experimental Treatment 4 Interventions

Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.

Group II: Placebo + Atezolizumab + CE Active Control 4 Interventions

Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.

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?

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

In the phase III SKYSCRAPER-02 study involving 490 patients with untreated extensive-stage small-cell lung cancer, the addition of tiragolumab to atezolizumab and chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS).

The combination treatment was well tolerated, with similar rates of immune-mediated adverse events between the tiragolumab and control groups, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. Rudin, CM., Liu, SV., Soo, RA., et al.[2023]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

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 65 patients with extensive-disease small-cell lung cancer, the combination of atezolizumab, carboplatin, and etoposide showed a high response rate of 73.8%, with 80.5% in elderly patients (median age 74 years).

Despite some significant hematological toxicities, such as decreased neutrophil counts in 61.1% of elderly patients, the treatment demonstrated acceptable safety and efficacy, suggesting it could be a preferred standard treatment for elderly patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Shiono, A., Imai, H., Wasamoto, S., et al.[2023]

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 phase 3 trial with 572 patients, atezolizumab significantly improved overall survival by 7.1 months compared to platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC) and high PD-L1 expression (20.2 months vs. 13.1 months).

Atezolizumab also demonstrated a favorable safety profile, with fewer grade 3 or 4 adverse events (30.1%) compared to chemotherapy (52.5%), indicating it may be a safer first-line treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. Herbst, RS., Giaccone, G., de Marinis, F., et al.[2022]

The combination of anti-PD1/PD-L1 immunotherapy with chemotherapy (carboplatin plus etoposide) significantly improves overall survival in patients with extensive-disease small-cell lung cancer (ED-SCLC), with a hazard ratio of 0.746 indicating a 25% reduction in the risk of death compared to chemotherapy alone.

Among various treatment combinations, nivolumab plus chemotherapy was identified as the most effective option for improving both overall survival and progression-free survival, outperforming the anti-CTLA-4 approach in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis. Mutlu, H., Bozcuk, H., Artaç, M., et al.[2023]

References

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

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. [2023]

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

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

5. 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]

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

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. [2023]

7. 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]

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

Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. [2022]

9. India pubmed.ncbi.nlm.nih.gov

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis. [2023]