Immunotherapy + Chemotherapy for Small Cell Lung Cancer

(CASPIAN Trial)

Recruiting at 183 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

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

Compensation: Varies

Number of Visits: 9

Duration: Approximately 18 weeks

987 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of combining durvalumab ± tremelimumab with platinum based chemotherapy (EP) followed by durvalumab ± tremelimumab maintenance therapy versus EP alone as first-line treatment in patients with extensive-stage small-cell lung cancer

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 on steroids or anti-convulsants for brain metastases, you must be stable off them for at least 1 month before starting the study treatment.

What data supports the effectiveness of the drug combination of immunotherapy and chemotherapy for small cell lung cancer?

Research shows that adding durvalumab to chemotherapy (carboplatin or cisplatin with etoposide) significantly improves overall survival in patients with extensive-stage small-cell lung cancer compared to chemotherapy alone. This combination is now a standard treatment option for this condition. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemotherapy safe for treating small cell lung cancer?

The combination of durvalumab and tremelimumab with chemotherapy (including drugs like cisplatin or carboplatin and etoposide) has been studied in clinical trials for lung cancer. These studies have not identified any new safety concerns, suggesting that the treatment is generally safe for humans. ^{2 4 5 6 7}

How is the drug combination of Durvalumab, Tremelimumab, and chemotherapy unique for treating small cell lung cancer?

This drug combination is unique because it includes immunotherapy drugs Durvalumab and Tremelimumab, which help the immune system fight cancer, alongside traditional chemotherapy drugs. The CASPIAN study showed that adding Durvalumab to chemotherapy significantly improved survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone. ^{1 2 4 5 6}

Research Team

Haiyi Jiang, M.D.

Principal Investigator

AstraZeneca

Eligibility Criteria

This trial is for adults with extensive-stage small cell lung cancer who have a life expectancy of at least 12 weeks, are in good physical condition (ECOG 0 or 1), and haven't had immune therapy before. They should be able to receive platinum-based chemo. Those with brain metastases must be stable without steroids or anti-convulsants for a month.

Inclusion Criteria

My cancer has spread widely, and any brain metastases are stable without needing steroids or anti-convulsants for over a month.

I am eligible for platinum-based chemotherapy as my first treatment.

I have not had treatments that boost the body's natural defenses to fight cancer, except for cancer vaccines.

Exclusion Criteria

I do not have active infections like TB, HIV, or hepatitis.

I have had or will have chest radiation before or after systemic therapy.

I have a condition related to my cancer that affects other parts of my body and needs treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab ± tremelimumab with platinum-based chemotherapy until disease progression or up to 6 cycles for EP alone

Approximately 18 weeks

Visits every 3 weeks for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

29-33 months

Tumor assessments at Week 6, Week 12, then every 8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Durvalumab
• Etoposide
• Tremelimumab

Trial Overview The study tests if adding durvalumab alone or with tremelimumab to standard platinum-based chemotherapy (carboplatin or cisplatin plus etoposide) improves outcomes compared to just the chemo. After initial treatment, patients may continue receiving the immunotherapy drugs as maintenance.

Participant Groups

Group I: Arm 2 Experimental Treatment 4 Interventions

durvalumab+EP (carboplatin or cisplatin + etoposide)

Group II: Arm 1 Experimental Treatment 5 Interventions

durvalumab+tremelimumab+EP (carboplatin or cisplatin + etoposide)

Group III: Arm 3 Active Control 3 Interventions

EP (carboplatin or cisplatin + etoposide)

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In the phase III CASPIAN trial involving previously untreated adults with extensive-stage small cell lung cancer (ES-SCLC), the addition of durvalumab to chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Durvalumab combined with etoposide and either carboplatin or cisplatin demonstrated a manageable safety profile, making it a valuable first-line treatment option and an accepted standard of care for patients with ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Extensive-Stage SCLC. Al-Salama, ZT.[2022]

In the phase III CASPIAN study, the combination of durvalumab with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer compared to etoposide plus platinum alone.

Patient-reported outcomes showed that the addition of durvalumab not only maintained quality of life but also delayed the worsening of key symptoms like appetite loss, cough, and fatigue, indicating a beneficial impact on patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Goldman, JW., Garassino, MC., Chen, Y., et al.[2021]

This study is investigating the combination of the anti-PD-L1 antibody durvalumab with carboplatin and etoposide in 56 previously untreated patients with extensive-stage small-cell lung cancer (ES-SCLC) and poor performance status (PS 2-3), aiming to assess its safety and efficacy.

The primary goal is to evaluate the tolerability of this treatment regimen, while secondary outcomes include survival rates and response to treatment, addressing a significant unmet medical need for patients with poor prognosis in ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin and etoposide plus durvalumab for previously untreated extensive-stage small-cell lung cancer (ES-SCLC) patients with a poor performance status (PS): NEJ045A study protocol. Asao, T., Watanabe, S., Tanaka, T., et al.[2022]

In the CASPIAN study involving 805 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of durvalumab and platinum-etoposide significantly improved overall survival compared to platinum-etoposide alone, with a median survival of 12.9 months versus 10.5 months.

However, adding tremelimumab to durvalumab and platinum-etoposide did not provide a significant survival benefit, indicating that durvalumab plus platinum-etoposide should be considered the new standard of care for first-line treatment of ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Goldman, JW., Dvorkin, M., Chen, Y., et al.[2021]

In the phase III CASPIAN study, durvalumab combined with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer, with a median overall survival of 12.9 months compared to 10.5 months for the control group.

After more than 3 years of follow-up, durvalumab plus etoposide showed a 36-month overall survival rate of 17.6%, indicating that this combination is a promising first-line treatment option for extensive-stage small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. Paz-Ares, L., Chen, Y., Reinmuth, N., et al.[2022]

In the phase III POSEIDON study, the combination of tremelimumab, an anti-CTLA-4 antibody, with durvalumab and chemotherapy showed increased antitumor activity and improved long-term survival in patients with first-line metastatic non-small cell lung cancer (mNSCLC).

Higher exposure to tremelimumab was associated with better progression-free survival (PFS) and overall survival (OS), but further analyses suggested that this relationship might be confounded, and no significant safety concerns were linked to tremelimumab exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Exposure-Response Analysis for the CTLA-4 Inhibitor Tremelimumab in Metastatic NSCLC Patients in the Phase III POSEIDON Study. He, JZ., Duval, V., Jauslin, P., et al.[2023]

References

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

Durvalumab: A Review in Extensive-Stage SCLC. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin and etoposide plus durvalumab for previously untreated extensive-stage small-cell lung cancer (ES-SCLC) patients with a poor performance status (PS): NEJ045A study protocol. [2022]

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

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. [2021]

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

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. [2020]

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

Population Pharmacokinetics and Exposure-Response Analysis for the CTLA-4 Inhibitor Tremelimumab in Metastatic NSCLC Patients in the Phase III POSEIDON Study. [2023]