AZD2811 + Durvalumab for Small Cell Lung Cancer

(TAZMAN Trial)

Not currently recruiting at 29 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with extensive stage small-cell lung cancer (ES-SCLC). The researchers aim to assess the safety and effectiveness of AZD2811 (an experimental treatment) and Durvalumab (an immunotherapy drug) when used together after initial chemotherapy. Participants must have ES-SCLC, be eligible for platinum-based chemotherapy with Durvalumab as their first treatment, and must not have received any prior immune therapy. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

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.

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

Research has shown that the combination of AZD2811 and durvalumab has been tested for safety in people with small cell lung cancer. Previous patients demonstrated that this combination can be tolerated, though reports of side effects exist. AZD2811 alone had limited success, with some patients not responding and the cancer worsening after a short time.

Durvalumab is already approved for other conditions, so its safety profile is well understood. Doctors know the side effects it can cause and how to manage them.

Overall, while some safety evidence exists for using these drugs together, discussing any concerns with a doctor is important. They can help explain the risks and benefits based on individual health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD2811 + Durvalumab for small cell lung cancer because it combines a novel drug delivery system with immunotherapy. Unlike standard treatments like Carboplatin and Etoposide, which focus mainly on directly attacking cancer cells, AZD2811 is a nanoparticle drug that allows for targeted delivery and controlled release, potentially reducing side effects and improving efficacy. Additionally, Durvalumab is an immune checkpoint inhibitor that helps the body's immune system better recognize and fight cancer cells, offering a promising new approach to treatment. This combination aims to enhance the effectiveness of traditional chemotherapy while harnessing the power of the immune system.

What evidence suggests that the AZD2811 and Durvalumab combination could be effective for small cell lung cancer?

This trial investigates the use of a combination of two drugs, AZD2811 and durvalumab, to treat extensive-stage small cell lung cancer. Participants will receive this combination during the maintenance phase, following an induction phase with durvalumab and platinum chemotherapy (either carboplatin or cisplatin, along with etoposide). Studies have found that AZD2811 alone wasn't very effective, but it might work better when combined with durvalumab. Durvalumab, a type of immunotherapy, helps the immune system fight cancer. The goal is to provide a more effective ongoing treatment to prevent the cancer from worsening. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04745689

Study of AZD2811 + Durvalumab in ES-SCLC Primary objective of this study is to evaluate the efficacy of AZD2811 and durvalumab in patients who have not progressed following induction therapy with ...

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6132C00001

Study of AZD2811 + durvalumab in ES-SCLC - TAZMAN Primary objective of this study is to evaluate the efficacy of AZD2811 and durvalumab in patients who have not progressed following induction therapy with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11002497/

Aurora kinase B inhibition in small-cell lung cancer This trial showed limited clinical efficacy of the drug as a monotherapy, with no objective response and a median progression-free survival of 1.6 months [95% ...

4. trial.medpath.com trial.medpath.com/clinical-trial/c21d5b9b107015bf/azd2811-durvalumab-maintenance-therapy-lung-cancer

Study of AZD2811 + Durvalumab in ES-SCLC | MedPath Primary objective of this study is to evaluate the efficacy of AZD2811 and durvalumab in patients who have not progressed following induction therapy with ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08551

Study of AZD2811 + Durvalumab in ES-SCLC - NCI A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04525391

Study Details | NCT04525391 | AZD2811 and Durvalumab ... This study is a single arm, open-label, multi-centre phase II study of AZD2811NP and durvalumab combination therapy in subjects with relapsed small cell lung ...