Pembrolizumab and Olaparib Treatment of Extensive Small Cell Lung Cancer (ES-SCLC)

NCT05623319 | Recruiting Phase 2

• 1 other identifier: IRST162.14
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 12

Brief Summary

This is an open-label, single arm, phase 2 trial enrolling patients with untreated Extensive-Stage Small-Cell Lung Cancer (ES SCLC), with a strong translational attitude.

Conditions

SCLC,Extensive Stage

Keywords

SCLC,Extensive Stage; Translational; Liquid Biopsy; Pembrolizumab; Olaparib

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Time from registration to the first documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by local site or death due to any cause, whichever occurs first.

  44 months

Secondary Outcomes (9)

• Objective response rate (ORR)

  36 months

• Immune-related Objective response rate (irORR).

  36 months

• Progression free survival (PFS) at 6, 12, and 24 months

  About at 6-12-24 months

• Overall Survival (OS)

  44 months

• Number of participants experiencing Adverse Events (AEs).

  44 months

Study Arms (1)

Pembrolizumab/Olaparib

EXPERIMENTAL

Patients will be treated with pembrolizumab plus chemotherapy during the Induction Phase. In case of responsive or stable disease, patients will enter the Maintenance Phase and will be treated with pembrolizumab plus olaparib until progression or up to a maximum of 35 cycles.

Drug: Pembrolizumab/Olaparib

Interventions

Pembrolizumab/Olaparib DRUG

Patients will receive pembrolizumab 200 mg 1q21 and chemotherapy -platinum compound (cisplatin 75 mg/m2 or carboplatin area under the curve of 5 mg per milliliter per minute) 1q21 plus etoposide 100 mg/m2 1-3q21- for 4 cycles (Induction Phase). In case of responsive or stable disease, patients will receive pembrolizumab 200 mg 1q21 plus olaparib 300 mg twice daily until progression (Maintenance Phase) or up to a maximum of 35 cycles.

Pembrolizumab/Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Male/female participants who are at least 18 years of age on the day of signing informed consent.
• Cytologically/histologically confirmed diagnosis of SCLC per the Veterans Administration Lung Study Group (VALG) staging system will be enrolled in this study. Patients must have extensive stage (ES) SCLC defined as Stage IV (T any, N any, M 1a/b/c) by the American Joint Committee on Cancer, Eighth Edition.
• Possibility of obtaining tissue sample, via a biopsy of the primary tumour or metastatic tumour tissue, within the 6 weeks prior to study entry. An archival biopsy is acceptable as long as there has been no intervening anticancer treatment since the time the biopsy was obtained to enrolment in this clinical study and as long as it was within 6 weeks of study entry. Tissue sample would consist of formalin-fixed, paraffin-embedded tumour tissue blocks, or, from formalin-fixed paraffin-embedded tumor tissue block, at least five re-cut, unstained sections of 5 μM thickness for immunohistochemical analysis and five unstained sections of 10 μM thickness for NGS, presented on slides or cell-block.
• No prior systemic treatment for ES-SCLC. Patients who have received prior chemo-radiotherapy for limited-stage SCLC must have been treated with curative intent and experienced a treatment free interval of at least 6 months since the last chemotherapy, radiotherapy, or chemoradiotherapy cycle from diagnosis of ES-SCLC.
• Patients with thoracic radiotherapy clinically indicated (e.g. mediastinal syndrome) could be enrolled providing they receive radiotherapy not before 15 days since the start of the experimental treatment. Patients who received radiation therapy to the lung fields that is \> 30 Gy within 6 months of the first dose of trial treatment, will be excluded.
• Presence of target lesions by RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of registration .
• Patients with paraneoplastic syndromes can be enrolled if an autoimmune origin can be excluded. Autoimmune origin will be defined according to local practice.
• Life expectancy ≥12 weeks.
• Capacity to swallow.
• Ability to comply with the study protocol, in the investigator's judgment.
• Have adequate organ function. Specimens must be collected within 10 days prior to the registration day.
• Negative human immunodeficiency virus (HIV) test at screening.
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive total HBcAb test.

You may not qualify if:

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Active or history of autoimmune disease or immune deficiency which has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover less than 10% of body surface area;
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids;
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months;
• Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computerized tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fredericia (QTcF) prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome. In case of significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident), acute events must happen not before than 3 months prior to initiation of study treatment.
• Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study.
• History of malignancy other than SCLC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as, adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, Stage I uterine cancer or non-muscle-invasive urothelial carcinoma (Ta - Tis - T1).

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

UO Oncologia Medica, IRST IRCCS

Meldola, Forlì Cesena, 47014, Italy

RECRUITING

Ospedale San Gerardo - ASST Monza

Monza, Monza E Brianza, 20900, Italy

RECRUITING

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, Pesaro Urbino, 61121, Italy

RECRUITING

IRCCS Istituto Tumori Giovanni Paolo II

Bari, 70124, Italy

RECRUITING

UO Oncologia, IRCCS Ospedale Sant'Orsola, AUSL Bologna

Bologna, 40138, Italy

RECRUITING

IRCCS Istituto Nazionale Tumori Fondazione "G. Pascale"

Napoli, 80131, Italy

RECRUITING

Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

RECRUITING

Azienda USL della Romagna - Osp. Santa Maria delle Croci

Ravenna, 48121, Italy

ACTIVE NOT RECRUITING

A.O. Arcispedale S. Maria Nuova IRCCS di Reggio Emilia

Reggio Emilia, Italy

RECRUITING

Azienda USL della Romagna - Osp. "Infermi" di Rimini

Rimini, 47923, Italy

ACTIVE NOT RECRUITING

Istituti Fisioterapici Ospitalieri - IFO -Ospedale Regina Elena

Roma, 00128, Italy

RECRUITING

ASST dei Sette Laghi - Osp. di Circolo e Fondazione Macchi

Varese, 21100, Italy

ACTIVE NOT RECRUITING

MeSH Terms

Interventions

pembrolizumab; olaparib

Study Officials

• Angelo Delmonte

  IRCCS IRST

  STUDY CHAIR

Central Study Contacts

Oriana Nanni

CONTACT

+390543739266; oriana.nanni@irst.emr.it

Bernadette Vertogen

CONTACT

+390544286058; bernadette.vertogen@irst.emr.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 21, 2022
• Study Start: March 27, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (12)