Immunotherapy for Small Cell Lung Cancer

(ADRIATIC Trial)

Not currently recruiting at 233 trial locations

Overseen By AstraZeneca Cancer Study, Local service

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Platinum, Etoposide

Disqualifiers: Extensive-stage SCLC, Autoimmune disorders, Infections, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the immunotherapy drugs Durvalumab and Tremelimumab can help treat small cell lung cancer (SCLC) after initial therapy. Researchers seek to discover if these medications can prevent cancer progression following chemotherapy and radiation. The study includes three groups: one receives Durvalumab and a placebo, another receives Durvalumab and Tremelimumab, and the last group receives only a placebo. The trial seeks participants with small cell lung cancer that has not worsened after initial chemotherapy and radiation treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance 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. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that durvalumab is generally safe for treating various solid cancers. Studies have found that patients typically tolerate it well, with no unexpected side effects when used after certain cancer treatments. In these studies, patients with lung cancer and other solid tumors received durvalumab, and most did not experience serious problems.

When combined with tremelimumab, durvalumab maintains an acceptable safety profile. While some side effects may occur, they are usually manageable. This combination has been linked to improvements in patients' conditions, with a generally tolerable safety level.

For those considering joining a trial with these treatments, past studies indicate that both drugs are usually well-tolerated. However, discussing any specific concerns or health conditions with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for small cell lung cancer because they harness the power of immunotherapy, which is different from the traditional chemotherapy options like cisplatin or etoposide. Durvalumab, an immune checkpoint inhibitor, works by blocking a protein that prevents the immune system from attacking cancer cells, thus allowing the body's defenses to target and destroy the cancer more effectively. When combined with Tremelimumab, another checkpoint inhibitor, this effect is potentially amplified, offering a new angle for treating this aggressive cancer type. Unlike conventional approaches, which can be highly toxic, these immunotherapy options aim to provide a more targeted treatment with the potential for fewer side effects.

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

Studies have shown that durvalumab, when used alone, can help treat small cell lung cancer (SCLC). Real-world evidence indicates that adding durvalumab to chemotherapy improves outcomes for SCLC patients. Research also suggests that durvalumab is safe after treatments like chemoradiation.

In this trial, one group of participants will receive a combination of durvalumab and tremelimumab. Early studies on this combination are promising, as both drugs enhance the immune system's ability to fight cancer. While more research is needed, initial findings suggest it could effectively treat this type of lung cancer. ^{1 4 5 6 7}

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 patients with limited-stage small cell lung cancer (stages I-III) who haven't worsened after chemoradiation. They must have completed a specific chemotherapy and radiotherapy regimen recently, be expected to live at least 12 weeks, and have an ECOG performance status of 0 or 1.

Inclusion Criteria

I've completed 4 cycles of specific chemo and radiotherapy recently.

My condition has not worsened after receiving combined chemotherapy and radiation.

I will have brain radiation after my initial cancer treatment, within 1 to 42 days before starting the trial medication.

Exclusion Criteria

I do not have any uncontrolled illnesses like lung disease.

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

I received chemotherapy and radiotherapy one after the other, with no overlap.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab or Durvalumab and Tremelimumab as consolidation treatment following chemoradiation therapy

16 weeks

4 visits (in-person) for combination therapy, followed by monthly visits for monotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Placebo
• Tremelimumab

Trial Overview The study tests Durvalumab alone or combined with Tremelimumab versus a placebo as additional treatment post-chemoradiation in phase III trials. It's randomized, double-blind, and includes multiple international centers.

How Is the Trial Designed?

Group I: Durvalumab + Tremelimumab Experimental Treatment 2 Interventions

Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab.

Group II: Durvalumab + Placebo Experimental Treatment 2 Interventions

Durvalumab monotherapy: Durvalumab (1500 mg intravenous \[IV\]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution.

Group III: Placebo + Placebo Placebo Group 1 Intervention

Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination.

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 a study involving 58 patients with advanced squamous non-small-cell lung cancer (sqNSCLC) who had previously progressed on anti-PD-(L)1 therapy, the combination of durvalumab and tremelimumab showed minimal efficacy, with only a 7% response rate in those with primary resistance and no responses in the acquired resistance cohort.

The treatment resulted in a median progression-free survival of about 2 months and an overall survival of approximately 7.6 to 7.7 months, indicating limited effectiveness in overcoming resistance to prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). Leighl, NB., Redman, MW., Rizvi, N., et al.[2023]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

The combination of durvalumab and tremelimumab was studied in 19 articles involving 2052 patients with solid tumors, showing some benefits over traditional chemotherapy in certain tumor types.

However, this combination did not consistently outperform durvalumab alone, indicating that while it may have potential, further research with larger and better-designed studies is needed to clarify its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review. Arru, C., De Miglio, MR., Cossu, A., et al.[2023]

In the phase 3 POSEIDON study involving 1013 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC), the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Patients receiving the combination treatment also experienced a longer time to deterioration in quality of life and various symptoms, indicating better overall health status compared to those on chemotherapy, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). Garon, EB., Cho, BC., Luft, A., et al.[2023]

In the phase 3 MYSTIC study involving 488 treatment-naïve patients with metastatic non-small-cell lung cancer, durvalumab alone or in combination with tremelimumab showed significant improvements in patient-reported outcomes (PROs) compared to chemotherapy, particularly in reducing fatigue and appetite loss.

Patients receiving durvalumab-containing treatments experienced a longer time to deterioration in quality of life and physical functioning, indicating that these treatments may help maintain better overall well-being without negatively impacting quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Garon, EB., Cho, BC., Reinmuth, N., et al.[2022]

In a safety run-in phase of the DURIGAST PRODIGE 59 study involving 11 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, 63.6% experienced significant adverse events, primarily neutropenia, indicating a notable safety concern with the treatment combination.

The combination of FOLFIRI with Durvalumab and/or Tremelimumab showed an expected safety profile, allowing progression to the randomized phase II study, although careful monitoring for serious adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. Evrard, C., Aparicio, T., Soularue, E., et al.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Patients with metastatic non-small-cell lung cancer who developed immune-mediated adverse events (imAEs) while treated with durvalumab showed significantly improved overall survival compared to those without imAEs, indicating a potential link between imAE development and treatment efficacy.

A predictive model was created using machine learning to identify patients at higher risk of developing imAEs, which could help tailor treatment strategies and enhance patient outcomes in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. Dey, A., Austin, M., Kluger, HM., et al.[2022]

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(24)00556-8/fulltext

215TiP A phase II study of durvalumab (MEDI 4736) ... DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance specifically in frail LD-SCLC pts who have not progressed following concomitant or ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9760036/

Forthcoming Phase II Study of Durvalumab (MEDI4736) Plus ... This is the first prospective study to evaluate the effects of an ICI with PE specifically in ES-SCLC patients with brain metastases.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423

NCT02087423 | A Global Study to Assess the Effects of ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8536

A phase II study of durvalumab (MEDI4736) immediately ... Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT367664

Real-world data of durvalumab plus chemotherapy for ... The aim of this study was to evaluate the efficacy of durvalumab plus chemotherapy in small cell lung cancer (SCLC) patients in real world experience.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(DURVALUMAB%20OR%20MEDI4736%20OR%20MEDI-4736%20OR%20Imfinzi))&rank=10

A Global Study to Assess the Effects of MEDI4736 ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...