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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemo-immunotherapy with durvalumab and ceralasertib for individuals with extensive stage small cell lung cancer. The goal is to determine how long patients live without cancer progression. Participants will begin with standard chemotherapy (including drugs like carboplatin and etoposide) and then transition to maintenance therapy with durvalumab and the oral medication ceralasertib. Suitable candidates have untreated small cell lung cancer that has metastasized and are ready to start chemotherapy. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Previous studies have shown that carboplatin and etoposide are safe for treating small cell lung cancer, with patients generally tolerating these drugs well. Research also shows their safety and effectiveness when combined with other treatments.

Studies indicate that durvalumab, another drug in this trial, is safe for many types of solid cancers, including lung cancer, and is well-tolerated when used alone or with other drugs.

Ceralasertib has undergone safety and tolerability studies, with reports suggesting it is safe at certain doses and can work well with other lung cancer treatments.

Overall, these treatments have been studied for safety in people with similar conditions. While side effects can occur, current evidence suggests they are generally manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for small cell lung cancer because it combines chemo-immunotherapy with innovative drugs, Durvalumab and Ceralasertib. Unlike standard treatments, which typically focus only on chemotherapy agents like Carboplatin and Etoposide, this approach adds Durvalumab to boost the immune system and Ceralasertib to disrupt cancer cell DNA repair. This dual-action strategy could potentially improve effectiveness and offer a new hope for patients by targeting the cancer more aggressively than current options.

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

Research has shown that using carboplatin and etoposide with durvalumab effectively treats extensive-stage small cell lung cancer (ES-SCLC). Studies have found that this combination can shrink tumors, reduce symptoms, and extend patient survival. Durvalumab is approved for the initial treatment of ES-SCLC and has demonstrated significant survival benefits. In this trial, participants will receive these treatments combined with ceralasertib. Ceralasertib is a newer drug that targets DNA damage repair in cells, potentially enhancing the effectiveness of chemotherapy and immunotherapy. Although less information is available on ceralasertib, its mechanism suggests it could improve treatment outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Muhammad Furqan

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

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

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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, 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]

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