Chemo-Immunotherapy + Durvalumab + Ceralasertib for Small Cell Lung Cancer

Recruiting at 4 trial locations

Overseen By Muhammad Furqan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Muhammad Furqan

Must be taking: Platinum-based chemotherapy

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Infection, Autoimmune disorders, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this single arm study is to estimate the progression free survival of previously-untreated patients with extensive stage small cell lung cancer. Patients will receive initial chemo-immunotherapy followed by maintenance therapy with durvalumab and oral ceralasertib.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention a required washout period (time without taking certain medications) for potent inhibitors or inducers of CYP3A4 before starting ceralasertib. It's best to discuss your current medications with the study team to ensure there are no interactions.

What data supports the effectiveness of the drug combination of chemo-immunotherapy, durvalumab, and ceralasertib for small cell lung cancer?

Research shows that adding durvalumab to chemotherapy significantly improves overall survival in patients with extensive-stage small-cell lung cancer compared to chemotherapy alone. This suggests that the combination of these drugs could be effective for treating this type of cancer. ^{1 2 3 4 5}

Is the combination of chemo-immunotherapy with durvalumab and ceralasertib safe for humans?

The combination of durvalumab with chemotherapy drugs like carboplatin and etoposide has been shown to have a manageable safety profile in patients with extensive-stage small-cell lung cancer, meaning it is generally safe for use in humans. ^{2 3 4 5 6}

What makes the drug combination of chemo-immunotherapy, durvalumab, and ceralasertib unique for treating small cell lung cancer?

This treatment is unique because it combines traditional chemotherapy (carboplatin and etoposide) with durvalumab, an immune-boosting drug, and ceralasertib, which may enhance the immune response, potentially improving survival in patients with extensive-stage small-cell lung cancer. ^{1 3 4 5 6}

Research Team

Muhammad Furqan

Principal Investigator

University of Iowa

Eligibility Criteria

Adults (18+) with untreated extensive stage small cell lung cancer suitable for platinum-based chemo (Carboplatin or Cisplatin with Etoposide). Must have measurable disease, proper organ function, and an ECOG Performance Status of 0-1. Women must use contraception and have a negative pregnancy test; men also need to agree to contraception. Excludes those with autoimmune diseases, prior SCLC therapy, certain infections like Hepatitis B/C or HIV, on strong CYP3A4 affecting drugs, severe nausea/vomiting issues, recent major surgery or live vaccines.

Inclusion Criteria

I am post-menopausal or not pregnant if of childbearing age.

I can swallow and keep down pills.

I am deemed fit for a specific chemotherapy for small cell lung cancer.

Exclusion Criteria

I have had a transplant of stem cells or an organ from another person.

Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

I am not on high-dose steroids or drugs that weaken my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive chemo-immunotherapy with Cisplatin or Carboplatin, Etoposide, and Durvalumab for 4 cycles

12 weeks

4 visits (in-person) every 3 weeks

Maintenance Therapy

Participants receive maintenance therapy with Durvalumab and oral Ceralasertib starting from Cycle 5

19 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Carboplatin
• Ceralasertib
• Durvalumab
• Etoposide

Trial Overview This study tests the effectiveness of initial chemo-immunotherapy followed by maintenance therapy using Durvalumab and oral Ceralasertib in patients who haven't been treated before for extensive stage small cell lung cancer. The goal is to see how long patients can live without their cancer getting worse.

Participant Groups

Group I: Cisplatin or Carboplatin + Etoposide + Durvalumab + Ceralasertib Experimental Treatment 5 Interventions

Initial Phase: Cycles 1-4 Cisplatin or Carboplatin: Day 1 Etoposide: Days 1-3 Durvalumab, 1500 mg: Day 1 q 3 weeks Maintenance Phase, Cycles 5+ Durvalumab, 1500 mg: Day 8 q 4 wks. Ceralasertib at 240mg po BID twice a day: Days 1-7

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?

Muhammad Furqan

Lead Sponsor

Trials

5

Recruited

130+

AstraZeneca

Industry 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 CASPIAN trial, first-line treatment with durvalumab plus platinum-etoposide significantly improved overall survival in patients with extensive-stage small cell lung cancer, showing consistent benefits regardless of PD-L1 expression or tissue tumor mutational burden status.

The study found that while PD-L1 expression may be a useful biomarker for treatment response, the overall survival benefit of durvalumab plus EP was similar across different PD-L1 subgroups, indicating that this treatment could be effective for a broad range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab ± tremelimumab + platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): outcomes by PD-L1 expression and tissue tumor mutational burden. Paz-Ares, L., Garassino, MC., Chen, Y., 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]

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, 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]

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 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]

References

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

Durvalumab ± tremelimumab + platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): outcomes by PD-L1 expression and tissue tumor mutational burden. [2023]

2. France pubmed.ncbi.nlm.nih.gov

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

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. 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]

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, 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]