Ceralasertib + Durvalumab for Lung Cancer

(LATIFY Trial)

Not currently recruiting at 250 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option combining ceralasertib (an experimental treatment) and durvalumab (an immunotherapy drug) for individuals with advanced lung cancer, specifically those whose cancer has progressed after previous treatments. The study compares this combination to the standard treatment, docetaxel, to determine which is more effective and safer. Suitable candidates have advanced non-small cell lung cancer (NSCLC), have undergone anti-PD-(L)1 therapy and platinum-based chemotherapy, and have no issues with basic daily activities. 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. However, it is important to discuss your current medications with the trial team to ensure they do not interfere with the study treatments.

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

Research shows that combining ceralasertib and durvalumab is generally safe for people with advanced non-small cell lung cancer (NSCLC). Previous patients found this combination effective without serious side effects. Some studies reported side effects like tiredness and nausea, but these are usually manageable. Additionally, durvalumab, one of the drugs in this combination, is already approved for treating some types of lung cancer, supporting its safety. Overall, research suggests that this treatment is safe for humans, with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Ceralasertib and Durvalumab for lung cancer because it brings a fresh approach to treatment. Unlike the standard chemotherapy option, Docetaxel, which targets rapidly dividing cells, Ceralasertib is an oral medication that inhibits a specific enzyme involved in DNA damage repair. This potentially enhances the cancer-fighting effects of Durvalumab, an immunotherapy that helps the immune system recognize and attack cancer cells. By using these two drugs together, there's hope to boost the body's natural defenses while directly disrupting cancer cell survival, offering a promising new strategy for patients.

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

Research has shown that combining ceralasertib and durvalumab, which participants in this trial may receive, may help treat non-small cell lung cancer (NSCLC). A previous study found that this combination worked well for patients with advanced NSCLC who had already tried other treatments, suggesting the combo therapy could be effective for these patients. Large reviews of multiple studies have also confirmed that durvalumab, especially when used with other treatments like ceralasertib, is effective and safe for advanced NSCLC. Overall, these findings suggest that using ceralasertib and durvalumab together might be a good option for patients with limited treatment choices. Meanwhile, another group in this trial will receive docetaxel monotherapy, a standard of care treatment. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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]

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 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]

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]

Citations

1. nature.com nature.com/articles/s41591-024-02808-y

Biomarker-directed targeted therapy plus durvalumab in ... Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. Benjamin Besse ORCID ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05450692

NCT05450692 | A Phase III Study of Ceralasertib Plus ... This study will assess the efficacy and safety of the combination of ceralasertib and durvalumab versus standard of care docetaxel in patients with locally ...

3. esmo.org esmo.org/oncology-news/efficacy-safety-and-translational-data-from-durvalumab-plus-ceralasertib-in-advanced-metastatic-nsclc-following-prior-failure-to-anti-pd1-pd-l1-and-platinum-doublet-therapy

Efficacy, Safety, and Translational Data from Durvalumab ... A phase II umbrella HUDSON study has demonstrated an efficacy signal with durvalumab plus ceralasertib in patients with advanced/metastatic non-small cell lung ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12238800/

Evaluation of the efficacy and safety of durvalumab ... Our meta-analysis confirmed the efficacy and safety of Durvalumab combination therapy in patients with advanced non-small cell lung cancer. The ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38351187/

Biomarker-directed targeted therapy plus durvalumab in ... Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial. Nat Med. 2024 Mar;30(3): ...