Atezolizumab + Chemotherapy for Small Cell Lung Cancer

(SKYSCRAPER-02 Trial)

No longer recruiting at 238 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of combining a new drug, tiragolumab, with atezolizumab (also known as Tecentriq, an immunotherapy drug) and chemotherapy for treating extensive-stage small cell lung cancer (ES-SCLC). Researchers aim to determine if this combination is more effective than using atezolizumab and chemotherapy with a placebo. Participants are divided into two groups: one receives the experimental drug tiragolumab, and the other receives a placebo during treatment. Individuals newly diagnosed with ES-SCLC who have not received previous systemic treatment for this condition might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking 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. 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.

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

Research shows that the combination of tiragolumab and atezolizumab is generally safe for people. In several studies, this treatment did not introduce any new safety problems. Participants experienced side effects similar to those expected with comparable treatments.

Atezolizumab, used in both treatment groups in the trial, has already been approved for other types of cancer. Doctors are familiar with its usual side effects, such as tiredness and nausea, which are typically manageable.

Carboplatin and etoposide are common chemotherapy drugs used for many years to treat different cancers. Their side effects, like hair loss and low blood cell counts, are well known, and doctors know how to handle them.

Overall, past studies have shown that the treatment combinations being tested have been well tolerated, with no unexpected safety issues reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for small cell lung cancer, which often include chemotherapy combinations like carboplatin and etoposide, the new treatment approach adds an innovative twist with tiragolumab. Tiragolumab is a novel immune checkpoint inhibitor that targets a protein called TIGIT, potentially enhancing the immune system's ability to fight cancer. Researchers are excited because this dual-target approach, combining tiragolumab with atezolizumab, another immune checkpoint inhibitor, might improve the effectiveness of the immune response against tumors. This combination could offer a new way to tackle small cell lung cancer by not only blocking cancer growth but also empowering the body's natural defenses.

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

This trial will compare two treatment arms for extensive-stage small cell lung cancer (ES-SCLC). One arm will receive a combination of tiragolumab and atezolizumab with chemotherapy, while the other will receive a placebo with atezolizumab and chemotherapy. Research has shown that combining tiragolumab and atezolizumab with chemotherapy hasn't provided significant benefits for treating ES-SCLC. In earlier studies, this combination didn't help patients live longer without disease progression or increase their overall lifespan compared to standard treatment. The treatments were generally well tolerated, with no unexpected side effects. However, evidence suggests that adding tiragolumab doesn't enhance treatment effectiveness. Currently, there isn't enough proof that this combination is superior to existing treatments. ^{1 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06267001

NCT06267001 | A Study of Tiragolumab Plus Atezolizumab ... The purpose of this study was to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo plus atezolizumab administered to ...

2. lungcancerstoday.com lungcancerstoday.com/post/officials-skyscraper-06-study-of-tiragolumab-plus-atezolizumab-in-nonsquamous-nsclc-intended-to-halt

SKYSCRAPER-06 Study of Tiragolumab Plus ... The study has been comparing first-line tiragolumab plus atezolizumab (Tecentriq) and chemotherapy with pembrolizumab and chemotherapy in ...

3. onclive.com onclive.com/view/tiragolumab-plus-atezolizumab-fails-to-meet-survival-end-points-in-previously-untreated-pd-l1-high-nsclc

Tiragolumab Plus Atezolizumab Fails to Meet Survival End ... First-line tiragolumab plus atezolizumab did not improve PFS and OS vs atezolizumab alone in PD-L1–high, unresectable or metastatic NSCLC.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37976444/

SKYSCRAPER-02: Tiragolumab in Combination ... - PubMed Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals.

5. gene.com gene.com/media/press-releases/15029/2024-07-03/genentech-provides-update-on-phase-iiiii

Genentech: Press Releases | Wednesday, Jul 3, 2024 The combination of tiragolumab plus Tecentriq and chemotherapy showed reduced efficacy in both PFS and OS compared to the comparator arm in the intent-to-treat ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01363

SKYSCRAPER-02: Tiragolumab in Combination With ... Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals.

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04725-2/fulltext

636P SKYSCRAPER-02C: Phase III study of atezolizumab ... A phase III study evaluating whether adding tira to atezo + CE improves survival outcomes in Chinese pts with ES-SCLC.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04294810

NCT04294810 | A Study of Tiragolumab in Combination ... The purpose of the study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in participants ...

9. targetedonc.com targetedonc.com/view/tiragolumab-plus-atezolizumab-fails-to-improve-outcomes-as-consolidation-in-nsclc

Tiragolumab Plus Atezolizumab Fails to Improve ... Tiragolumab plus atezolizumab did not improve progression-free survival compared to durvalumab in stage III NSCLC patients post-cCRT. Median ...