Ceralasertib + Durvalumab for Lung Cancer

(LATIFY Trial)

Recruiting at 210 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, ATR inhibitors

Disqualifiers: Autoimmune disorders, Mixed SCLC/NSCLC, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

594 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new combination of drugs (ceralasertib and durvalumab) against a standard treatment (docetaxel) in patients with advanced lung cancer who didn't respond to previous treatments. The new combination aims to weaken cancer cells and boost the immune system, while the standard treatment directly kills the cancer cells.

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, it is important to discuss your current medications with the trial team to ensure they do not interfere with the study treatments.

What data supports the effectiveness of the drug combination Ceralasertib and Durvalumab for lung cancer?

Durvalumab has shown effectiveness in treating non-small cell lung cancer (NSCLC), especially in patients with high PD-L1 expression, and is approved for use after chemoradiation in locally advanced cases. It has demonstrated improved survival rates when combined with chemotherapy in advanced NSCLC. ^{1 2 3 4 5}

Is the combination of Ceralasertib and Durvalumab safe for humans?

Durvalumab, one of the drugs in the combination, has been studied for safety in various cancers, including lung cancer. It is generally considered to have acceptable safety, but it can cause side effects like lung issues, which sometimes lead to stopping the treatment. The safety of the combination with Ceralasertib specifically may not be fully established yet. ^{1 3 6 7 8}

What makes the drug combination of Ceralasertib and Durvalumab unique for lung cancer treatment?

This treatment combines Ceralasertib, which may enhance the effects of Durvalumab, an immune therapy that helps the body's immune system attack cancer cells. Durvalumab is already used after chemoradiation in certain lung cancer patients, and this combination could offer a new approach by potentially improving the immune response against cancer. ^{2 3 7 9 10}

Eligibility Criteria

This trial is for adults with advanced NSCLC who have already tried anti-PD-(L)1 and platinum-based chemotherapy without success. They should not be pregnant, must have a good performance status (able to carry out daily activities), adequate organ function, and no severe weight loss due to cancer. People with certain other cancers or those who've had serious side effects from previous immunotherapies can't join.

Inclusion Criteria

Women who can have babies need to have a negative pregnancy blood test.

My cancer has worsened despite my most recent treatment.

My lung cancer is advanced or has spread, as confirmed by tests.

Exclusion Criteria

My lung cancer is a mix of small cell and non-small cell types.

I had cancer before, but it was treated over 5 years ago and hasn't come back.

I have had more than one platinum-based chemotherapy for my cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ceralasertib plus durvalumab combination therapy or docetaxel monotherapy in 28-day or 21-day cycles, respectively

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 3 months following disease progression or treatment discontinuation

Up to 3 years

Treatment Details

Interventions

• Ceralasertib
• Docetaxel
• Durvalumab

Trial Overview The study compares the effectiveness of Ceralasertib combined with Durvalumab against the standard treatment Docetaxel in patients whose NSCLC has worsened despite prior therapies. It aims to see if this new combination can improve outcomes for these patients.

Participant Groups

Group I: Group A: Ceralasertib plus durvalumab combination therapy Experimental Treatment 2 Interventions

Participants will be administered ceralasertib orally followed by durvalumab administered intravenously.

Group II: Group B: Docetaxel monotherapy Active Control 1 Intervention

Participants will be administered docetaxel (standard of care) administered intravenously.

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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

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]

Durvalumab, an immune checkpoint inhibitor, has shown promising efficacy in treating advanced non-small cell lung cancer (NSCLC) in early phase trials, demonstrating a good safety profile.

The PACIFIC trial has successfully met its primary endpoint, indicating that durvalumab may be an important part of future treatment strategies for NSCLC, with ongoing studies potentially confirming its superiority over current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI 4736 (durvalumab) in non-small cell lung cancer. Jeanson, A., Barlesi, F.[2021]

In a systematic review of 18 phase III clinical trials involving 12,172 lung cancer patients, the use of PD-(L)1 immune-checkpoint inhibitors (ICIs) did not show a significant increase in rheumatic immune-related adverse events (irAEs) compared to controls, suggesting these events may be underreported in clinical settings.

However, patients receiving ICIs experienced significantly higher rates of severe back pain and, when combined with chemotherapy, a notable increase in arthralgia, indicating that while overall rheumatic irAEs are low, specific types of pain are associated with ICI treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and meta-analysis. Veccia, A., Kostine, M., Tison, A., et al.[2022]

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]

In a study involving 576 patients with unresectable stage III non-small cell lung cancer (NSCLC), the PD-L1 inhibitor durvalumab showed a favorable safety profile, with only 22.7% of patients experiencing adverse events, primarily mild esophagitis.

Durvalumab treatment after concurrent chemoradiotherapy (cCRT) resulted in consistent outcomes across both PD-L1 positive and negative patients, indicating its potential as a standard care option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program. Avrillon, V., Daniel, C., Boisselier, P., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

4. Ireland 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). [2023]

5. England pubmed.ncbi.nlm.nih.gov

MEDI 4736 (durvalumab) in non-small cell lung cancer. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and meta-analysis. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Durvalumab-induced Lung Toxicity Using a Spontaneous Reporting Database. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

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

Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program. [2022]