Ceralasertib + Durvalumab for Non-Small Cell Lung Cancer

Recruiting at 148 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Chemo-immunotherapy

Must not be taking: Steroids, Live vaccines

Disqualifiers: EGFR/ALK mutations, ILD, 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

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

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

630 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, AZD6738 (Ceralasertib) and durvalumab, to determine if they work better together than durvalumab alone in treating non-small cell lung cancer. AZD6738 may inhibit tumor growth by blocking certain enzymes, while durvalumab, a type of protein, aids the immune system in targeting cancer cells. The goal is to assess whether adding AZD6738 can help patients remain cancer-free longer after chemotherapy and surgery. Patients with stage II to IIIB non-small cell lung cancer who have already undergone chemotherapy and surgery might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on ongoing steroids at a dose of prednisone 10 mg or higher, and you must not have received a live vaccine within 30 days before starting the trial.

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

Research shows that the combination of ceralasertib and durvalumab is generally well-tolerated by patients. Some studies have found that while side effects may occur, they are usually manageable, and the treatment is considered safe overall. For example, in some patients, the combination proved effective for a longer duration without causing major problems.

Durvalumab is already used in other treatments, providing a known safety record. When combined with ceralasertib, some patients experienced blood-related side effects, but these were usually manageable, allowing doctors to treat or control them effectively.

For those considering participation in a study with this combination, existing data suggests it is safe for many patients, though individual experiences may vary. Always discuss potential risks and benefits with a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a fresh approach to tackling non-small cell lung cancer. Unlike most treatments that typically focus on chemotherapy or targeted therapy alone, this trial combines durvalumab, an immunotherapy that boosts the body's immune response to fight cancer, with ceralasertib (AZD6738), an ATR kinase inhibitor that disrupts cancer cell repair mechanisms, potentially leading to more effective cancer cell death. This combination could enhance the effectiveness of the immune system's attack on cancer cells, offering new hope for improved outcomes. By targeting the cancer in two distinct ways, these treatments might provide a more comprehensive assault on tumor growth and resilience compared to standard therapies.

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

This trial will compare the effects of durvalumab alone with the combination of durvalumab and ceralasertib for treating non-small cell lung cancer. Studies have shown that combining ceralasertib with durvalumab appears promising for this type of cancer. Early results suggest that this combination can help control the cancer for a longer period. Research indicates that ceralasertib may enhance durvalumab's effectiveness by improving its ability to find and destroy cancer cells. Reports suggest that this combination has manageable side effects, which is encouraging for patients. Durvalumab alone is already known to help prevent cancer from spreading by targeting specific proteins that aid cancer cell growth. Adding ceralasertib may enhance this effect, potentially leading to longer periods without cancer progression. ^{1 2 3 4 6}

Who Is on the Research Team?

Dwight H Owen

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for patients with stage II to select stage IIIB non-small cell lung cancer who've finished at least 3 cycles of chemo-immunotherapy and surgery within the last 4-12 weeks. They must not have a complete response to treatment post-surgery, as those are directed to another study.

Inclusion Criteria

I had surgery for my condition and can start treatment within 4-12 weeks after.

I did not achieve complete tumor removal with surgery.

I completed surgery with no cancer left after chemo-immunotherapy for certain stages of lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab and/or AZD6738 following surgery. Treatment cycles repeat every 28 days for 12 cycles.

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 12 weeks for 2 years, then every 24 weeks until year 5, and annually until 10 years from randomization.

10 years

What Are the Treatments Tested in This Trial?

Interventions

• AZD6738 (Ceralasertib)
• Durvalumab

Trial Overview The trial tests adding AZD6738 (Ceralasertib) to durvalumab immunotherapy versus using durvalumab alone after chemotherapy and surgery. The goal is to see if this combination can extend the time patients remain free from cancer.

How Is the Trial Designed?

Group I: Arm B (Durvalumab and AZD6738) Experimental Treatment 5 Interventions

Starting 4-12 weeks after surgery, patients receive AZD6738 PO BID on days 1-7 and durvalumab IV over 60 minutes on day 8 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and blood sample collection throughout the study and may undergo echocardiography as clinically indicated.

Group II: Arm A (Durvalumab) Active Control 4 Interventions

Starting 4-12 weeks after surgery, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and blood sample collection throughout the study and may undergo echocardiography as clinically indicated.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

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

Biomarker-directed targeted therapy plus durvalumab in ... These results suggest a potential sensitizing effect from the addition of ceralasertib to durvalumab in post-ICB NSCLC, and our data provide ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8104

A phase II, open-label, combination therapy of durvalumab ... Ceralasertib and durvalumab combination therapy have demonstrated durable responses in select patients with manageable hematologic toxicity.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06732401

NCT06732401 | Testing the Addition of AZD6738 ... Adding AZD6738 to durvalumab may increase time without cancer in patients with non-small cell lung cancer, following treatment with chemotherapy and surgery.

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): ...

6. jto.org jto.org/article/S1556-0864(23)00956-5/fulltext

MA06.06 A Phase II Trial of Ceralasertib and Durvalumab ... These data provide further preliminary support for the efficacy signals seen with the ceralasertib/durvalumab combination in ICB pre-treated NSCLC.