Niraparib Added to Anti-PD-L1 Antibody Maintenance in SLFN11-positive, Extensive-disease SCLC

Launched by ETOP IBCSG PARTNERS FOUNDATION · Jan 30, 2023

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ClinConnect Summary

The RAISE clinical trial is studying a new treatment approach for patients with extensive-stage small cell lung cancer (SCLC) who have a specific marker called SLFN11. In this trial, researchers are adding a medication called niraparib to the standard maintenance treatment with an anti-PD-L1 antibody. This study aims to see if combining these treatments can help patients whose cancer has not worsened after receiving the usual first-line chemotherapy and immunotherapy.

To be eligible for this trial, participants must be adults aged 18 and older with confirmed extensive-stage SCLC that hasn't progressed after standard treatment. They need to have high levels of SLFN11 in their tumor tissue and must have provided the necessary consent for both screening and trial participation. Participants can expect to take niraparib once daily alongside their ongoing maintenance treatment. The trial is currently recruiting and aims to evaluate the effectiveness and safety of this combination therapy. It's important for potential participants to discuss any other health conditions or medications with their doctor to determine if they meet the criteria for joining the study.

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Eligibility criteria

• Inclusion Criteria:
• • Inclusion criteria for SLFN11-expression testing
• • Written IC part 1: for SLFN11-screening must be signed and dated by the patient and the investigator prior to sending any tumour material to the central laboratory.
• • Histologically or cytologically confirmed ED-SCLC (stage IV according to the 8th TNM classification).
• • Availability of FFPE tumour tissue for screening.
• • Inclusion criteria for trial participation
• • Written IC part 2: for trial participation must be signed and dated by the patient and the investigator prior to any trial-related intervention.
• * 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.
• • ED-SCLC must not have progressed during or after standard chemo-immunotherapy (as per RECIST v1.1).
• • Patients must be candidates for ongoing maintenance treatment with immune-checkpoint inhibition.
• * Adequate haematological function:
• * Adequate renal function:
• * Adequate liver function:
• • ECOG PS 0-2
• • Age ≥18 years
• • Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 4 weeks before enrolment and within 3 days before treatment start.
• Exclusion Criteria:
• • Symptomatic brain metastases
• • Any clinically active cancer, other than SCLC Exception: malignancies with negligible risk of metastases or death (e.g. 5-year OS rate of \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or stage I uterine cancer. Hormonal therapy for non-metastatic prostate or ductal carcinoma in situ is allowed.
• • Consolidating thoracic radiotherapy. Palliative radiotherapy to the brain or to bones is allowed.
• • 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.
• • The patient must be considered stable and hypertension medically controlled.
• • 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.
• • Treated with live vaccine within 30 days before enrolment.
• • Hypersensitivity to niraparib or any of its excipients (e.g., tartrazine).
• • Women who are pregnant or in the period of lactation.
• • Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the trial and within the required timelines after last dose of niraparib treatment.
• • Judgment by the investigator that the patient is unlikely to comply with trial procedures, restrictions and requirements.