Personalized Treatments for Small Cell Lung Cancer

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SWOG Cancer Research Network

Must be taking: Platinum, Etoposide, Durvalumab

Must not be taking: Atezolizumab, Pembrolizumab, Nivolumab

Disqualifiers: Pregnancy, Organ transplant, Autoimmune disease, 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: Unknown

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat extensive stage small cell lung cancer (ES-SCLC) by personalizing treatment plans based on specific features of the cancer cells. Researchers will use biomarker tests to determine which treatment might work best for each patient, focusing on drugs like durvalumab (an immunotherapy drug), saruparib (a type of PARP inhibitor), ceralasertib (an experimental treatment), and monalizumab (an immunotherapy drug). The study aims to assess whether these personalized treatments can control the cancer after initial therapy. It suits individuals with ES-SCLC who are ready to try maintenance therapy after completing initial treatment with specific drugs. As a Phase 2 trial, this research measures the effectiveness of the treatment in an initial, smaller group, offering a chance to benefit from personalized therapies.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot receive any non-study chemotherapy, immunotherapy, or hormonal therapy for small cell lung cancer while participating. It's best to discuss your current medications with the study team.

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

Previous studies have shown that durvalumab is generally well-tolerated by patients with lung cancer. Common side effects include fatigue and cough. Research on combining monalizumab with durvalumab also indicates a manageable safety profile, with side effects like headaches and joint pain.

For the combination of durvalumab and ceralasertib, studies have demonstrated a manageable safety profile. Patients have experienced side effects such as nausea and reduced appetite.

When durvalumab is combined with saruparib, it has shown a consistent safety profile. Reported side effects include tiredness and nausea, similar to when each drug is used alone.

These findings are general observations from past studies, and individual experiences may vary. ^{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 (SCLC) because they are tailored to specific subtypes of the disease, potentially offering more personalized and effective care. Unlike conventional treatments like chemotherapy, which broadly targets rapidly dividing cells, these investigational treatments use a combination of drugs with unique mechanisms. For example, durvalumab and monalizumab are immune checkpoint inhibitors, which help the immune system better recognize and attack cancer cells. Ceralasertib is an ATR inhibitor, which disrupts cancer cell's DNA repair mechanisms, making them more vulnerable to treatment. Saruparib, a PARP inhibitor, also targets DNA repair pathways, particularly in patients with specific genetic markers. By focusing on these novel approaches, researchers hope to improve outcomes and provide more targeted options for patients with SCLC.

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

This trial will evaluate different treatment combinations for small cell lung cancer. Studies have shown that combining durvalumab and monalizumab, which participants in one arm of this trial may receive, can help lung cancer patients live longer without their cancer worsening. Another arm will test durvalumab and ceralasertib together, and research indicates that this combination has lasting effects, meaning the benefits endure for some patients. For participants in another arm receiving durvalumab and saruparib, evidence supports that this combination is effective, especially in advanced lung cancer, as it helps control the disease. Each combination boosts the immune system's ability to fight cancer. Overall, these treatments show promise in preventing small cell lung cancer from worsening. ^{1 2 3 5 6}

Who Is on the Research Team?

Anne C Chiang

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with extensive stage small cell lung cancer (ES-SCLC) who've started but not completed more than three cycles of specific chemotherapy and have not used certain other immunotherapies or investigational drugs. It's not for those with a history of limited stage SCLC, another malignancy that could affect the trial's outcomes, or planning to use non-study treatments.

Inclusion Criteria

I am taking bisphosphonates for bone metastases.

I don't have another cancer that could affect this treatment's safety or results.

I have not used experimental drugs for small cell lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 3 years

Induction

Patients receive a platinum compound plus etoposide and durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles.

16-24 weeks

Consolidation

Patients may undergo thoracic radiation as clinically indicated.

Maintenance

Patients receive maintenance therapy with durvalumab, potentially combined with saruparib, ceralasertib, or monalizumab, depending on cohort assignment.

28 days per cycle, ongoing in the absence of disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Ceralasertib
• Durvalumab
• Monalizumab
• Saruparib

Trial Overview The study uses biomarker tests on tumor tissue to select personalized maintenance treatments post-initial therapy. Tested drugs include durvalumab, saruparib, ceralasertib, and monalizumab targeting different mechanisms like immune response and DNA repair in cancer cells.

How Is the Trial Designed?

Group I: Cohort C, Arm 2 (durvalumab, monalizumab) Experimental Treatment 9 Interventions

Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.

Group II: Cohort C, Arm 1 (durvalumab) Experimental Treatment 8 Interventions

Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.

Group III: Cohort B, Arm 2 (durvalumab, ceralasertib) Experimental Treatment 9 Interventions

Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.

Group IV: Cohort B, Arm 1 (durvalumab) Experimental Treatment 8 Interventions

Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.

Group V: Cohort A, Arm 2 (durvalumab, saruparib) Experimental Treatment 9 Interventions

Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.

Group VI: Cohort A, Arm 1 (durvalumab) Experimental Treatment 8 Interventions

Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

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

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

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

Biomarker-directed targeted therapy plus durvalumab in ... Disease control rates at 12 and 24 weeks, respectively, were 50.6% and 35.4% with durvalumab–ceralasertib and 32.3% and 15.9% with the pooled ...

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

Biomarker-directed targeted therapy plus durvalumab in ... Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to ...

4. 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 total of 268 patients received treatment. Greatest clinical benefit was observed with durvalumab plus ceralasertib; objective response rate ...

5. mdanderson.org mdanderson.org/newsroom/biomarker-directed-combination-effective-in-immunotherapy-resistant-lung-cancer.h00-159695178.html

Biomarker-directed combination effective in ... Phase II trial finds durvalumab plus ceralasertib boosted immune response and improved outcomes in patients with lung cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04699838?term=NCT02937818%20NCT03428607%20NCT04699838&rank=1

Study Details | NCT04699838 | Chemo-Immunotherapy ... The primary objective of this single arm study is to estimate the progression free survival of previously-untreated patients with extensive stage small cell ...