Immunotherapy + Chemotherapy for Small Cell Lung Cancer

(CASPIAN Trial)

Not currently recruiting at 227 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids, Anticonvulsants

Disqualifiers: Autoimmune disorders, Active infection, 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

Compensation: Varies

Number of Visits: 9

Duration: Approximately 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of combining immunotherapy with chemotherapy for individuals with extensive-stage small cell lung cancer. The study compares different combinations of the medicines durvalumab (an immunotherapy drug), tremelimumab (an immunotherapy drug), carboplatin, cisplatin, and etoposide to determine the most effective first treatment. Individuals diagnosed with extensive-stage small cell lung cancer who have not yet received immune therapy might be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity 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, 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.

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

Research has shown that combining durvalumab with tremelimumab and chemotherapy drugs like carboplatin and etoposide is generally well-tolerated by patients with extensive-stage small cell lung cancer. Some studies have found these treatments to be effective and mostly safe.

One study found that durvalumab with chemotherapy worked well and was well-tolerated, even in a group of Japanese patients with this type of lung cancer. Another study focused on the safety of combining durvalumab and tremelimumab with chemotherapy, indicating that the side effects were generally manageable.

The FDA has already approved durvalumab, when used with chemotherapy, for treating extensive-stage small cell lung cancer, confirming it has passed strict safety tests for this use.

Overall, while any treatment can have side effects, these studies suggest that the combination therapies being tested are generally safe for people with this type of lung cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy options for small cell lung cancer, which typically include drugs like carboplatin, cisplatin, and etoposide, the new combination treatments bring immunotherapy into the mix. Researchers are excited about these treatments because they incorporate durvalumab and tremelimumab, which are immune checkpoint inhibitors. These drugs work by unleashing the body's immune system to better recognize and attack cancer cells, potentially offering a more powerful response against the cancer. This combination of chemotherapy with immunotherapy could enhance treatment effectiveness and improve patient outcomes compared to traditional chemotherapy alone.

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

Research has shown that adding durvalumab to the usual chemotherapy drugs, platinum and etoposide, extends the lives of patients with extensive-stage small-cell lung cancer (ES-SCLC). The FDA has approved this combination for initial treatment. In this trial, participants in Arm 2 will receive durvalumab with chemotherapy, while Arm 1 will include both durvalumab and tremelimumab with chemotherapy. Studies have demonstrated that adding tremelimumab to durvalumab and chemotherapy also improves overall survival and provides longer cancer control. These treatments offer promising options for people with ES-SCLC, potentially extending life and managing the disease more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Haiyi Jiang, M.D.

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9807442/

Phase II study of durvalumab (MEDI 4736) plus carboplatin ... This prospective, multicenter, single‐arm study was designed to evaluate the safety and efficacy of durvalumab plus carboplatin and etoposide in untreated ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06419179?term=olaparib&cond=Lung%20Cancer&viewType=Table&rank=1

Study Details | NCT06419179 | Maintenance Durvalumab ... Study treatment ( olaparib and durvalumab) starts with the initiation of maintenance therapy and is administered at a 28-day cycle until progression, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S246829422500108X

First-line durvalumab plus platinum–etoposide in ... Given the efficacy observed in the CASPIAN study, the combination of durvalumab with EP chemotherapy has received approval as a first-line therapy for ES-SCLC ...

4. imfinzihcp.com imfinzihcp.com/sclc/extensive-stage/efficacy.html

IMFINZI® (durvalumab) Efficacy & Clinical Trials for 1L ES- ... The ONLY FDA-approved IO combination in first-line ES-SCLC with 3-YEAR overall survival data from a randomized Phase III study

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1111/1759-7714.14727

Phase II study of durvalumab (MEDI 4736) plus carboplatin ... This prospective, multicenter, single-arm study was designed to evaluate the safety and efficacy of durvalumab plus carboplatin and etoposide in untreated ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05856695

Study Details | NCT05856695 | Durvalumab Plus ... The current study is intended to be a "proof of concept" to evaluate the potential value of synergy between paclitaxel carboplatin and immunotherapy.

7. esmoopen.com esmoopen.com/article/S2059-7029(25)01194-9/fulltext

a multicenter, single-arm phase II trial (LOGiK2001, SPEED) Platinum plus etoposide with durvalumab for extensive-stage small-cell lung cancer with untreated brain metastases: a multicenter, single-arm phase II trial

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8134304/

First-line durvalumab plus platinum-etoposide in extensive ... First-line durvalumab plus EP was effective and well tolerated in Japanese patients with ES-SCLC. Despite the small size of the Japan subgroup, results were ...

9. imfinzihcp.com imfinzihcp.com/sclc/extensive-stage.html

FDA-approved IO combination - in first-line ES-SCLC ... Learn about IMFINZI® (durvalumab) as a treatment option for adult patients with 1L extensive-stage small cell lung cancer and its 3-year OS data.

10. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04472949?term=NCT04472949&draw=2&rank=1

NCT04472949 | Thoracic Radiotherapy Plus Maintenance ... Secondary objective is to evaluate the safety of tRT combined with maintenance durvalumab in SCLC after chemo-immunotherapy. For this trial durvalumab is the ...