Serplulimab + Chemotherapy for Small Cell Lung Cancer

Recruiting at 121 trial locations

Overseen By Wallace Akerley

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Shanghai Henlius Biotech

Must not be taking: Psychotropic drugs

Disqualifiers: Mixed SCLC, Severe allergy, Myocardial infarction, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 months

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two different treatment combinations for patients with extensive-stage small cell lung cancer who have not received any prior treatment. One group will receive a new drug called Serplulimab along with standard chemotherapy, while the other group will receive an existing drug called Atezolizumab with the same chemotherapy. Both immunotherapy drugs aim to help the immune system fight cancer, and the chemotherapy drugs work by killing cancer cells. Atezolizumab has been shown to improve survival in small-cell lung cancer when combined with chemotherapy, changing the standard first-line therapy.

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, if you are using denosumab for bone metastases, you must switch to bisphosphonate therapy before and during the trial.

What data supports the effectiveness of the drug combination Serplulimab plus chemotherapy for small cell lung cancer?

The ASTRUM-005 trial showed that adding Serplulimab to chemotherapy improved survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone. ^{1 2 3 4 5}

Is the combination of Serplulimab and chemotherapy generally safe for humans?

Serplulimab combined with chemotherapy has been shown to have a manageable safety profile in clinical trials for various cancers, including lung and esophageal cancers. While it can cause serious side effects in some patients, the overall safety is considered acceptable compared to chemotherapy alone. ^{1 3 6 7 8}

How is the drug Serplulimab plus chemotherapy different for treating small cell lung cancer?

Serplulimab is an anti-PD-1 antibody that helps the immune system fight cancer by reducing immunosuppression, and when combined with chemotherapy, it has shown survival benefits for patients with extensive-stage small-cell lung cancer compared to chemotherapy alone. This combination is particularly novel as there is no standard treatment for transformed small cell lung cancer, making it a promising option for patients with this aggressive disease. ^{1 2 3 9 10}

Eligibility Criteria

This trial is for US patients newly diagnosed with extensive-stage small cell lung cancer (ES-SCLC) who are fully mobile and have not received prior treatment. Eligible participants must not have other active cancers, except certain cured skin or in situ cancers, and should test negative for HIV, Hepatitis B/C. They cannot join if they've had a solid organ or bone marrow transplant, cervical/bladder/skin cancer, peripheral neuropathy, or brain metastasis.

Inclusion Criteria

I have no active cancer and no history of cancer in the last 5 years, except for certain skin, bladder, prostate, cervical, or breast cancers that were treated and cured.

Answer yes if you do not have HIV, Hepatitis B or Hepatitis C

I do not have brain metastasis or carcinomatous meningitis.

Exclusion Criteria

I have been diagnosed with cervical cancer.

You have been diagnosed with HIV, Hepatitis B, or Hepatitis C.

I have been newly diagnosed with extensive-stage small cell lung cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Serplulimab or Atezolizumab plus chemotherapy (carboplatin-etoposide)

14 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

24 months

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• HLX10

Trial Overview The study compares the efficacy and safety of two treatments: Serplulimab plus chemotherapy (carboplatin-etoposide) versus Atezolizumab plus the same chemotherapy in untreated ES-SCLC patients. Participants will be randomly assigned to either Arm A (Serplulimab group) or Arm B (Atezolizumab control group).

Participant Groups

Group I: Serplulimab + chemotherapy Experimental Treatment 1 Intervention

Serplulimab + chemotherapy (carboplatin-etoposide)

Group II: Atezolizumab + chemotherapy Active Control 1 Intervention

Atezolizumab + chemotherapy (carboplatin-etoposide)

HLX10 is already approved in China, European Union for the following indications:

Approved in China as Hansizhuang for:

• Microsatellite Instability-High (MSI-H) solid tumors
• Squamous non-small cell lung cancer (sqNSCLC)
• Extensive-stage small cell lung cancer (ES-SCLC)
• Esophageal squamous cell carcinoma (ESCC)

Approved in European Union as Hetronifly for:

• Extensive-stage small cell lung cancer (ES-SCLC)

Who Is Running the Clinical Trial?

Shanghai Henlius Biotech

Lead Sponsor

Trials

100

Recruited

19,200+

Dr. Jason Zhu

Shanghai Henlius Biotech

Chief Executive Officer since 2023

MBA from Yale University

Dr. Jun Zhu

Shanghai Henlius Biotech

Chief Medical Officer

MD from an unspecified institution

Findings from Research

This ongoing phase II clinical trial is evaluating the combination of serplulimab with chemotherapy (etoposide and carboplatin) in 36 patients with transformed small cell lung cancer (T-SCLC) that originated from EGFR-mutant non-small cell lung cancer (NSCLC).

The primary goal of the study is to assess progression-free survival, with secondary goals including overall survival and safety, addressing the urgent need for effective treatments in this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study. Huang, J., Zhang, XH., Cai, Y., et al.[2023]

The combination of serplulimab and chemotherapy (etoposide and carboplatin) significantly improves survival outcomes in patients with extensive-stage small-cell lung cancer (ES-SCLC), yielding 1.217 quality-adjusted life-years (QALYs) compared to 0.885 QALYs with chemotherapy alone.

From a cost-effectiveness perspective, the combination treatment has an incremental cost-effectiveness ratio (ICER) of $12,077 per QALY, making it a cost-effective first-line option for ES-SCLC patients in China, especially for specific subgroups like former smokers and those with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: A cost-effectiveness analysis. Zhu, Y., Liu, K., Qin, Q., et al.[2023]

Serplulimab is an anti-PD-1 antibody that stimulates immune responses by counteracting PD-1-related immunosuppression, making it a promising treatment for solid tumors.

It received its first approval in China on March 25, 2022, specifically for adult patients with advanced unresectable or metastatic microsatellite instability-high (MSI-H) solid tumors that did not respond to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serplulimab: First Approval. Lee, A.[2022]

The addition of serplulimab to chemotherapy for extensive-stage small cell lung cancer (SCLC) improved survival by 0.25 life-years and 0.15 quality-adjusted life-years (QALYs), but significantly increased treatment costs by $26,402.

The cost-effectiveness analysis revealed an incremental cost-effectiveness ratio (ICER) of $179,161 per QALY, indicating that serplulimab plus chemotherapy is not cost-effective in China, unless price discounts are applied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of serplulimab as first-line therapy for extensive-stage small cell lung cancer in China. Xiang, G., Jiang, T., Gan, L., et al.[2023]

In a phase II study involving 21 patients with PD-L1-positive advanced cervical cancer, the combination of serplulimab and nab-paclitaxel showed a promising objective response rate (ORR) of 57.1%, indicating significant efficacy in this previously treated population.

The treatment was associated with a manageable safety profile, with 81.0% of patients experiencing grade ≥3 treatment-emergent adverse events, suggesting that while the therapy is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of serplulimab plus nab-paclitaxel in previously treated patients with PD-L1-positive advanced cervical cancer: a phase II, single-arm study. An, J., Li, X., Wang, J., et al.[2023]

In a network meta-analysis of six clinical trials involving 3662 patients, immune checkpoint inhibitors combined with chemotherapy showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone for extensive-stage small cell lung cancer (ES-SCLC).

Among the combinations studied, serplulimab plus chemotherapy demonstrated the best survival benefits, outperforming other combinations like ipilimumab plus chemotherapy, while both serplulimab and adebrelimab showed promising efficacy and safety profiles, although the evidence level for these comparisons is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line immune checkpoint inhibitors combined with chemotherapy for extensive-stage small cell lung cancer: A network meta-analysis. Wang, S., Li, Y., Liu, Z., et al.[2023]

In a meta-analysis of 14 studies, PD-1/PD-L1 inhibitors showed a significantly lower risk of treatment-related death compared to control groups, with a risk ratio of 0.37, indicating a safer profile for lung cancer patients.

While PD-1/PD-L1 inhibitors alone had a lower overall rate of adverse events compared to chemotherapy, combining them with chemotherapy increased the risk of adverse events leading to treatment discontinuation (RR = 1.68).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The overall safety evaluation of programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) treatment for lung cancer patients: An updated systematic review and meta-analysis. Shang, H., Zhang, Z., Feng, A., et al.[2022]

In a phase 3 trial involving 551 patients with advanced esophageal squamous cell carcinoma (ESCC), the combination of serplulimab (an anti-PD-1 antibody) and chemotherapy significantly improved progression-free survival (PFS) compared to placebo plus chemotherapy, with a median PFS of 5.8 months versus 5.3 months.

The same combination also significantly prolonged overall survival (OS), with a median OS of 15.3 months for serplulimab plus chemotherapy compared to 11.8 months for the placebo group, while maintaining a manageable safety profile with similar rates of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial. Song, Y., Zhang, B., Xin, D., et al.[2023]

Serplulimab is projected to be a cost-effective first-line therapy for extensive-stage small-cell lung cancer in both the US and China, with an incremental cost-effectiveness ratio (ICER) of $106,757 in the US and $33,392 in China, based on a model analyzing data from 746 patients.

The study suggests that serplulimab would be cost-effective at a price below $762.11 per 100 mg in the US and below $373.37 per 100 mg in China, providing a pricing strategy that could guide decision-makers and clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serplulimab Plus Chemotherapy vs Chemotherapy for Treatment of US and Chinese Patients with Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis to Inform Drug Pricing. Shao, T., Zhao, M., Liang, L., et al.[2023]

In a study evaluating the cost-effectiveness of serplulimab plus chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) in China, the treatment increased life expectancy by 0.826 years and quality-adjusted life-years (QALYs) by 0.436, but had a high incremental cost-effectiveness ratio (ICER) of $120,149/QALY, indicating it is not cost-effective at standard willingness-to-pay thresholds.

Despite showing clinical benefits and a relative safety profile, serplulimab plus chemotherapy was deemed not cost-effective for ES-SCLC patients unless the cost of serplulimab is significantly reduced, suggesting that pricing strategies could improve its economic viability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of first-line serplulimab combined with chemotherapy for extensive-stage small cell lung cancer. Liang, X., Chen, X., Li, H., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: A cost-effectiveness analysis. [2023]

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

Serplulimab: First Approval. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of serplulimab as first-line therapy for extensive-stage small cell lung cancer in China. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of serplulimab plus nab-paclitaxel in previously treated patients with PD-L1-positive advanced cervical cancer: a phase II, single-arm study. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line immune checkpoint inhibitors combined with chemotherapy for extensive-stage small cell lung cancer: A network meta-analysis. [2023]

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

The overall safety evaluation of programmed cell death/programmed cell death ligand 1 (PD-1/PD-L1) treatment for lung cancer patients: An updated systematic review and meta-analysis. [2022]

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

First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial. [2023]

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

Serplulimab Plus Chemotherapy vs Chemotherapy for Treatment of US and Chinese Patients with Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis to Inform Drug Pricing. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of first-line serplulimab combined with chemotherapy for extensive-stage small cell lung cancer. [2023]