Niraparib with Anti-PD-L1 for SLFN11-positive Extensive-stage SCLC

A Single-arm Phase II Trial of the Addition of Niraparib to Anti-PD-L1 Antibody Maintenance in Patients With SLFN11-positive, Extensive-disease Small Cell Lung Cancer.

This study is testing if adding a pill called niraparib to an existing treatment can help people with a specific type of advanced small cell lung cancer feel better after their initial therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: ETOP IBCSG Partners Foundation (Research network)
• Drugs / interventions: atezolizumab, durvalumab, chemotherapy, immunotherapy
• Locations: 18 sites (Angers and 17 other locations)
• Trial ID: NCT05718323 on ClinicalTrials.gov

What this trial studies

This international, multicenter, single-arm phase II trial evaluates the effectiveness of adding niraparib, an oral medication, to maintenance therapy with an anti-PD-L1 antibody in patients with SLFN11-positive extensive-stage small cell lung cancer (ED-SCLC) who have not experienced disease progression after standard first-line chemo-immunotherapy. The trial aims to determine if this combination can improve clinical outcomes for these patients. Participants must have confirmed high SLFN11 expression and provide tumor tissue for screening.

Who should consider this trial

Good fit: Ideal candidates are patients with extensive-stage small cell lung cancer who have high SLFN11 expression and have not progressed after first-line treatment.

Not a fit: Patients with low SLFN11 expression or those who have progressed after first-line treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and quality of life for patients with SLFN11-positive extensive-stage SCLC.

How similar studies have performed: While this approach is novel in combining niraparib with anti-PD-L1 therapy for this specific patient population, similar studies have shown promise in other cancer types.

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.

Where this trial is running

Angers and 17 other locations

• CHU - Angers — Angers, France (Recruiting)
• Centre Hospitalier d'Avignon — Avignon, France (Recruiting)
• Caen - CHU — Caen, France (Recruiting)
• Lyon - Centre Léon Bérard — Lyon, France (Not_yet_recruiting)
• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) — Meldola, Italy (Recruiting)
• Instituto Europeo di Oncologia (IEO) — Milan, Italy (Not_yet_recruiting)
• Santa Maria della Misericordia Hospital — Perugia, Italy (Recruiting)
• AULSS2 Marca Trevigiana Treviso — Treviso, Italy (Not_yet_recruiting)
• Complejo Hospitalario Universitario a Coruña — A Coruña, Spain (Not_yet_recruiting)
• Complejo Hospitalario de Jaén — Jaén, Spain (Recruiting)
• Hospital Universitario Puerta de Hierro — Madrid, Spain (Recruiting)
• Kantonsspital Baden — Baden, Switzerland (Recruiting)
• University Hospital Basel — Basel, Switzerland (Recruiting)
• Inselspital Bern — Bern, Switzerland (Recruiting)
• Kantonsspital St. Gallen — Sankt Gallen, Switzerland (Recruiting)
• Centre Hospitalier du Valais Romand — Sion, Switzerland (Recruiting)
• Bürgerspital Solothurn — Solothurn, Switzerland (Recruiting)
• Kantonsspital Winterthur — Winterthur, Switzerland (Recruiting)

Study contacts

• Study coordinator: Heidi Roschitzki, PhD

Conditions SCLC,Extensive Stage; SLFN11-positive