AZD2811 + Durvalumab for Small Cell Lung Cancer

(TAZMAN Trial)

Recruiting at 25 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Platinum-based chemotherapy

Must not be taking: Systemic steroids, Immunosuppressive agents

Disqualifiers: Autoimmune disorders, Active infection, 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: 18

31 Participants Needed

Trial Summary

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 medications for autoimmune disorders or infections like tuberculosis, HIV, or hepatitis, you might need to discuss this with the trial team.

What data supports the effectiveness of the drug combination AZD2811 + Durvalumab for Small Cell Lung Cancer?

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

What safety data exists for the combination of AZD2811, Durvalumab, Carboplatin, Cisplatin, and Etoposide in humans?

The combination of Carboplatin and Etoposide has been studied in thoracic cancer, showing that severe blood-related side effects were the main concern, but other side effects were mild. Cisplatin combined with Etoposide was more active but also more toxic, causing more blood and kidney-related side effects compared to Carboplatin with Etoposide. In small cell lung cancer, a combination of Cisplatin, Carboplatin, and Etoposide showed blood-related side effects as the main limiting factor, but gastrointestinal side effects were manageable. ^{6 7 8 9 10}

What makes the drug AZD2811 + Durvalumab unique for treating small cell lung cancer?

The combination of AZD2811 with Durvalumab is unique because Durvalumab, an anti-PD-L1 antibody, has shown to improve overall survival when added to standard chemotherapy (carboplatin or cisplatin with etoposide) for extensive-stage small cell lung cancer, offering a new standard of care for patients with this condition. ^{1 2 5 11 12}

What is the purpose of this trial?

This trial tests a combination of two drugs, AZD2811 and Durvalumab, to maintain cancer control in adults with advanced small-cell lung cancer who responded well to earlier treatment. AZD2811 stops cancer cell growth, and Durvalumab helps the immune system fight the cancer. Durvalumab has shown survival benefits in various cancers, including non-small cell lung cancer.

Eligibility Criteria

This trial is for adults with extensive stage small-cell lung cancer (ES-SCLC) who are fit to receive platinum-based chemotherapy and Durvalumab as a first treatment. They should have a life expectancy of at least 12 weeks, be in good physical condition (ECOG 0 or 1), and not have had immune therapy before. People with prior chest radiation, active infections like TB or hepatitis, autoimmune diseases, uncontrolled illnesses, or certain paraneoplastic syndromes can't join.

Inclusion Criteria

Life expectancy ≥12 weeks at Day 1.

I am fully active or restricted in physically strenuous activity but can do light work.

I have never received immune therapy.

Exclusion Criteria

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

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

I have or had an autoimmune or inflammatory disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Participants receive platinum-based chemotherapy combined with durvalumab

6-8 weeks

Every 3 weeks (in-person)

Maintenance

Participants receive AZD2811 and durvalumab until disease progression or unacceptable toxicity

Up to 12 months

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 18 months

Every 8 weeks (in-person)

Treatment Details

Interventions

• AZD2811
• Carboplatin
• Cisplatin
• Durvalumab
• Etoposide

Trial Overview The study tests AZD2811 combined with Durvalumab as maintenance therapy after initial treatment with platinum-based chemo plus Durvalumab for ES-SCLC. It's an open-label Phase II trial where all participants receive the same experimental drugs to assess their effectiveness and safety.

Participant Groups

Group I: AZD2811 + Durvalumab Experimental Treatment 5 Interventions

Induction: Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin \& Etoposide) Maintenance: AZD2811 + Durvalumab

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 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 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, 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]

The combination of etoposide (VP 16) and cis-diamminedichloroplatinum (DDP) showed poor overall antitumor effects against Lewis lung carcinoma cell lines, with high acute toxicity observed.

Administering VP 16 before DDP resulted in a significant reduction in metastasis while maintaining acceptable levels of toxicity, suggesting a potential strategy for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etoposide prior to cis-diamminedichloroplatinum in combination chemotherapy: in vitro and in vivo studies. Zupi, G., Greco, C., Sacchi, A., et al.[2019]

A systematic review of 45 studies involving 16,141 cases found that various platinum-based chemotherapy regimens for incurable non-small cell lung cancer (NSCLC) did not show significant differences in overall survival rates, indicating that multiple regimens can be considered effective.

Specifically, regimens like Carboplatin plus Paclitaxel and Bevacizumab were used as a common comparator, and other combinations such as Cisplatin plus Tegafur gimeracil oteracil and Carboplatin plus S1 were also found to be acceptable first-choice treatments without significantly poorer survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis. Horita, N., Nagashima, A., Nakashima, K., et al.[2022]

In a trial involving 228 patients with advanced non-small-cell lung cancer, cisplatin (CDDP) combined with etoposide showed a higher objective response rate (27%) compared to carboplatin (CBDCA) with etoposide (16%), although this difference was not statistically significant (P = .07).

Cisplatin treatment was associated with significantly increased toxicity, particularly myelosuppression and renal function impairment, indicating that while it may be more effective, it also poses greater risks compared to carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. Klastersky, J., Sculier, JP., Lacroix, H., et al.[2017]

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]

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]

References

1. 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]

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

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

3. 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]

4. Japan pubmed.ncbi.nlm.nih.gov

First-line durvalumab plus platinum-etoposide in extensive-stage small-cell lung cancer: CASPIAN Japan subgroup analysis. [2021]

5. 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]

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

Etoposide prior to cis-diamminedichloroplatinum in combination chemotherapy: in vitro and in vivo studies. [2019]

7. England pubmed.ncbi.nlm.nih.gov

The best platinum regimens for chemo-naive incurable non-small cell lung cancer: network meta-analysis. [2022]

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

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Phase I study of a carboplatin-etoposide combination in advanced thoracic cancer. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

[Phase I/II study of a combination regimen composed of cisplatin, carboplatin and etoposide against small cell lung cancer]. [2013]

11. 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]

12. 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]