ETOP 23-22 RAISE: A single-arm phase II study of the addition of niraparib to anti-PD-L1 antibody maintenance in patients with SLFN11-positive, extensive-disease small cell lung cancer.
- Trial ID
- 2022-502092-33-00
- Protocol
- ETOP 23-22 RAISE
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to assess the clinical efficacy of adding **niraparib** to anti-PD-L1 monoclonal antibody maintenance treatment in patients with SLFN11-positive extensive-disease small cell lung cancer (ED-SCLC) that has not progressed following standard first-line chemo-immunotherapy. This evaluation is clinically relevant as it aims to enhance treatment outcomes in a subset of SCLC patients characterized by high SLFN11 expression, potentially improving survival rates and quality of life.
Participants
The clinical trial involves a total of **14 participants** diagnosed with **extensive-disease small cell lung cancer** (ED-SCLC) exhibiting high **SLFN11-expression**. The study population includes both male and female subjects, aged 18 years and older, who have not shown disease progression following standard first-line chemo-immunotherapy. Participants were selected based on their histologically or cytologically confirmed ED-SCLC and the availability of FFPE tumor tissue for central testing of SLFN11. The trial does not include a vulnerable population. Participants are required to have adequate hematological, renal, and liver function, and an ECOG performance status of 0-2. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to evaluate the efficacy of adding niraparib to anti-PD-L1 monoclonal antibody maintenance treatment in this specific patient group.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of adding **niraparib** to anti-PD-L1 monoclonal antibody maintenance treatment in patients with SLFN11-positive extensive-disease small cell lung cancer (ED-SCLC). This is a single-arm, phase II study with an estimated duration from January 2024 to January 2026. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on histological or cytological confirmation of ED-SCLC and high SLFN11 expression. Participants must have completed standard first-line chemo-immunotherapy without disease progression and be candidates for maintenance treatment with immune-checkpoint inhibition.
The trial design includes regular follow-up visits to monitor progression-free survival (PFS) and overall survival (OS), as well as to assess disease control rate (DCR) and adverse events according to CTCAE v5.0. The primary endpoint is the PFS rate at 3 months, evaluated by investigator assessment using RECIST v1.1 criteria. Secondary endpoints include PFS, OS, DCR, and adverse events. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 25 months, depending on individual response and disease progression.
Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or withdrawal of consent. The trial involves the administration of **atezolizumab** or **durvalumab** via intravenous infusion, alongside oral administration of **niraparib tosilate monohydrate**. The study aims to provide insights into the potential benefits of combining PARP inhibitors with immunotherapy in this patient population.
Treatment
The clinical trial involves the administration of **IMFINZI** (durvalumab), a concentrate for solution for infusion, with a concentration of 50 mg/mL. This pharmaceutical form is administered via **intravenous infusion**. The maximum daily dose is 1500 mg, with a total maximum dose of 39,000 mg over a treatment period of 25 weeks. Durvalumab is a protein-based active substance, specifically classified as "Protein - Other." The product is manufactured by AstraZeneca AB and is authorized for use in the European Union.
Another treatment used in the trial is **Tecentriq** (atezolizumab), available in two formulations: 1,200 mg and 840 mg concentrates for solution for infusion. Both formulations are administered through intravenous infusion. The maximum daily dose for atezolizumab is 1680 mg, with a total maximum dose of 42,000 mg over a 25-week period. Atezolizumab is also a protein-based active substance, categorized as "Protein - Other." This product is manufactured by Roche Registration GmbH and holds authorization in the European Union.
The experimental medication **Niraparib Tosilate Monohydrate** is administered in tablet form. It is a highly selective poly adenosine diphosphate (ADP)-ribose polymerase (PARP)-1 and -2 inhibitor. The maximum daily dose is 300 mg, with a total maximum dose of 228,000 mg over a 25-week period. Niraparib is a chemically derived active substance and is produced by GlaxoSmithKline. This medication is designated as an orphan drug, indicating its use in rare conditions.
Throughout the trial, participant compliance with the dosing schedule is monitored to ensure adherence to the treatment regimen. The trial aims to evaluate the efficacy of adding niraparib to anti-PD-L1 monoclonal antibody maintenance treatment in patients with SLFN11-positive extensive-disease small cell lung cancer (ED-SCLC) that has not progressed following standard first-line chemo-immunotherapy.
Efficacy
The clinical trial aims to assess the efficacy of adding **niraparib** to anti-PD-L1 monoclonal antibody maintenance treatment in patients with SLFN11-positive extensive-disease small cell lung cancer (ED-SCLC). The primary endpoint for evaluating efficacy is the progression-free survival (PFS) rate at 3 months, as assessed by investigators according to RECIST v1.1 criteria. Secondary endpoints include overall survival (OS), disease control rate (DCR) by investigator assessment, and adverse events according to CTCAE v5.0.
Efficacy parameters will be measured and collected at specified timepoints throughout the trial. The PFS rate at 3 months will be a critical measure, with additional assessments of OS and DCR conducted to provide a comprehensive evaluation of treatment impact. Investigator assessments will be utilized to ensure consistency and reliability in the evaluation of disease progression and control. The trial is designed to provide robust data on the clinical benefits of the treatment regimen, with a focus on maintaining rigorous standards for data collection and analysis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Inclusion criteria for SLFN11-expression testing • Histologically or cytologically confirmed ED-SCLC (stage IV according to the 8th TNM classification). • Availability of FFPE tumour tissue for central testing of SLFN11. • Written IC for SLFN11-screening must be signed and dated by the patient and the investigator prior to sending any tumour material to the central laboratory. Most important inclusion criteria for trial participation (See Section 7.2 for the complete list): • High SLFN11-expression on FFPE tumour material SLFN11-expression is determined at the central screening laboratory in Basel. Overexpression is defined as detectable protein expression by IHC in ≥20% of tumour cells. • Patients must have received standard first-line chemo-immunotherapy, consisting of 4 cycles of platinum-etoposide chemotherapy in combination with an anti-PD-L1 antibody (atezolizumab or durvalumab). Patients who started the immunotherapy at chemotherapy cycle 2, are eligible. • Patients must not have progressed on the standard chemo-immunotherapy (as per RECIST v1.1) • Patients must be candidates for maintenance treatment with immune-checkpoint inhibition. • Adequate haematological, renal and liver function • ECOG PS 0-2 • Age ≥18 years • Written IC for trial participation must be signed and dated by the patient and the investigator prior to any trial-related intervention
Exclusion Criteria
- Most important exclusion criteria (See Section 7.3 for the complete list): • Symptomatic brain metastases • Any clinically active cancer, other than SCLC • Consolidating thoracic radiotherapy • History of idiopathic pulmonary fibrosis, organising pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. • Any lung disease requiring systemic steroids in doses of >10 mg prednisolone (or equivalent dose of other steroid). • Any serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) which in the opinion of the investigator, would compromise the patient’s ability to complete the trial or interfere with the evaluation of the efficacy and safety of the protocol treatment. • Inadequately controlled hypertension, defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >95 mmHg. • History of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). • Prior Reversible Encephalopathy Syndrome (PRES). • Severe renal or hepatic impairment. • Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels. • Treatment with live vaccine within 30 days before enrolment. • Judgment by the investigator that the patient is unlikely to comply with trial procedures, restrictions and requirements.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 01 Jan 2024 | 8 |
 Germany | Recruiting | 01 Jan 2024 | 5 |
 Italy | Recruiting | 01 Jan 2024 | 8 |
 Romania | Not Recruiting | 01 Jan 2024 | 4 |
 Spain | Recruiting | 01 Jan 2024 | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IMFINZI 50 mg/mL concentrate for solution for infusion. | Other | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 1500 | 25 | PRD6651663 |
Tecentriq 1 200 mg concentrate for solution for infusion | Other | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 1680 | 25 | PRD5434939 |
IMFINZI 50 mg/mL concentrate for solution for infusion. | Other | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 1500 | 25 | PRD6651398 |
Tecentriq 840 mg concentrate for solution for infusion | Other | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 1680 | 25 | PRD7537922 |