SCLC,Extensive StagePhase 2THORNCT05623319
Pembrolizumab and Olaparib Treatment of Extensive Small Cell Lung Cancer (ES-SCLC)
A Phase 2 study testing Pembrolizumab/Olaparib in people with SCLC,Extensive Stage, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 12 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SCLC,Extensive Stage
- What is being tested?
- Pembrolizumab/Olaparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 12 sitesItaly
- Study dates
- 27 Mar 2023to Jul 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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;
Show all 32Show fewer
- 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).
- History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Active infection requiring systemic therapy.
- Known history of active Bacillus Tuberculosis (TB).
- Treatment with investigational therapy within 28 days prior to initiation of study treatment.
- Patient who has received prior therapy with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, anti-Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4), anti-OX40, anti-Cluster of Differentiation 137 (CD137), anti-CD27).
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2 (IL-2)) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment.
- Any previous treatment with a PARP inhibitor, including Olaparib.
- Concomitant use of known strong Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
- Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, olaparib and/or any of their excipients.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
- Known allergy or hypersensitivity to carboplatin or etoposide.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has had an allogenic tissue/solid organ transplant.
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Italy12 sites, 9 recruiting
- Recruiting
IRCCS Istituto Tumori Giovanni Paolo II
Bari, 70124
Vito Longo, MD
- Recruiting
UO Oncologia, IRCCS Ospedale Sant'Orsola, AUSL Bologna
Bologna, 40138
Giuseppe Lamberti, MD
- Recruiting
UO Oncologia Medica, IRST IRCCS
Meldola, Forlì Cesena, 47014
Angelo Delmonte, MD
- Recruiting
Ospedale San Gerardo - ASST Monza
Monza, Monza E Brianza, 20900
Diego Cortinovis
Diego Cortinovis, MD
- Recruiting
IRCCS Istituto Nazionale Tumori Fondazione "G. Pascale"
Naples, 80131
Alessandro Morabito
Alessandro Morabito, MD
- Recruiting
Istituto Oncologico Veneto IRCCS
Padova, 35128
Giulia Pasello
Giulia Pasello, MD
- Recruiting
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro, Pesaro Urbino, 61121
Rita Chiari
Rita Chiari, MD
- Active, not recruiting
Azienda USL della Romagna - Osp. Santa Maria delle Croci
Ravenna, 48121
- Recruiting
A.O. Arcispedale S. Maria Nuova IRCCS di Reggio Emilia
Reggio Emilia
Francesca Zanelli, MD
Francesca Zanelli, MD
- Active, not recruiting
Azienda USL della Romagna - Osp. "Infermi" di Rimini
Rimini, 47923
- Recruiting
Istituti Fisioterapici Ospitalieri - IFO -Ospedale Regina Elena
Roma, 00128
Federico Cappuzzo
Federico Cappuzzo, MD
- Active, not recruiting
ASST dei Sette Laghi - Osp. di Circolo e Fondazione Macchi
Varese, 21100
About this study
Official title: Phase 2 Trial of Translational Approach to First Line cHemoimmunotherapy Followed by Maintenance With pembrOlizumab and Olaparib in Extensive-Stage Small-Cell Lung CanceR.
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.
Read the detailed description
SCLC is a very aggressive disease with an overall survival (OS) of 12 months in the extensive stage (ES). Platinum-based as the first line of treatment has an overall response rate (ORR) of approximately 70% with a progression-free survival (PFS) of 5.5 months and an OS of almost 10 months. Prophylactic cranial irradiation, performed in order to prevent progression in brain, one of the major sites of recurrence, was associated with an increase in median disease-free survival of 12.0-14.7 weeks and in median OS of 5.4-6.7 months with a 1-year survival rate of 27.1%. At recurrence few therapeutic options are available. In order to improve clinical results, several strategies are under evaluation. Given the strong activity shown in several settings, immunotherapy is studied both as a single agent and in combinations.
Pembrolizumab has shown as maintenance after chemotherapy a PFS of 6.9 months in Programmed Cell Death 1 Ligand 1 (PD-L1) positive patients and as a monotherapy in 2nd and further lines an ORR of 19.3%, with major responses in PD-L1 positive patients and 61% of responders lasting ≥18 months. Recently the addition to standard chemotherapy of atezolizumab in patients with untreated ES-SCLC has led to an improvement of 2 months in OS (12.3 in the combo arms vs. 10.3 months in the control arm) and a slight improvement in PFS (5.2 vs. 4.3 months, respectively), without new safety data. Similarly addition of durvalumab to standard chemotherapy has led to a 2.7 months OS improvement (13 in the combo arms vs. 10.3 months in the control arm) with a relevant improvement in ORR (79.5 vs 70.3% respectively), without any improvement in PFS. Finally pembrolizumab combined with chemotherapy has shown significant improvement in PFS (hazard ratio (HR), 0.75; 95% confidence interval (CI), 0.61-0.91) but not in OS. Finally, considering the role of DNA damage repair systems in the tumorigenesis of SCLC, Olaparib has been also evaluated together with durvalumab in pre-treated ES-SCLC obtaining a clinical benefit of 21.1% and confirmed responses or stable disease for ≥8 months. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Despite biologic knowledge is growing, no clinically relevant molecular features have been identified. Recent publications in fact have proposed a new classification of SCLC in 3 major subgroups according to the expression of the neuronal basic helix-loop-helix transcription factors achaete-scute homologue 1 (ASCL1), involved in the neuroendocrine characterization, and the neurogenic differentiation factor 1 (NEUROD1). The so-called "classic type" shows expression of ASCL1, the "variant type" expresses NEUROD1 and the third type is negative for both the two previous biomarkers. In terms of gene profiling these subgroups are distinct but without a clear prognostic and predictive role. No driver mutations have been found. Many pathways are under evaluations. In particular Poly(ADP-Ribose) Polymerase (PARP) protein levels are up - regulated in SCLC relative to other lung cancers. In particular, Poly(ADP-Ribose) Polymerase 1 (PARP1) has been found to be highly expressed at both the messenger RNA (mRNA) and protein levels in SCLC samples. Given these data the combination proposed (Induction Phase with platinum/etoposide/pembrolizumab followed by a Maintenance Phase with pembrolizumab/olaparib) may be a new therapeutic option to be explored for patients. Moreover the evaluation of molecular features performed before, during and after this treatment may produce new evidence for further clinical trials.
The primary objective of the study is to evaluate the efficacy of chemo-immunotherapy induction followed by maintenance with pembrolizumab and olaparib in terms of Progression-free Survival (PFS).
Patients with extensive stage (ES) SCLC will receive pembrolizumab 200 mg 1q21 with 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.
Patients will be accrued for a period of 24 months and follow-up will continue for a period of 12 months after the last patient is enrolled.
The Kaplan-Meier approach will be used to estimate PFS.
- Conditions
- SCLC,Extensive Stage
- Being tested
- Pembrolizumab/Olaparib
- Keywords
- SCLC,Extensive Stage, Translational, Liquid Biopsy, Pembrolizumab, Olaparib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab/OlaparibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pembrolizumab/Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 44 months
Secondary outcomes (9)
Objective response rate (ORR)
Percentage of patients who have a confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1) during the induction and the maintenance phases of treatment.
Measured: 36 months
Immune-related Objective response rate (irORR).
Percentage of patients achieving a complete response (CR) or partial response (PR), according to immune-modified RECIST 1.1 criteria, during the induction and the maintenance phases of treatment.
Measured: 36 months
Progression free survival (PFS) at 6, 12, and 24 months
Percentage of patients alive and progression-free at 6, 12, and 24 months.
Measured: About at 6-12-24 months
Overall Survival (OS)
Time from registration to death due to any cause
Measured: 44 months
Number of participants experiencing Adverse Events (AEs).
Number of participants discontinuing study drugs due to AEs. Toxicity rate: percentage of patients experiencing a specific adverse event of grade 3-5, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.
Measured: 44 months
PD-L1 analysis
Evaluation of Programmed Cell Death 1 Ligand (PD-L1) expression on biopsy and blood samples collected before, during and after the treatment. It will be investigated the association of this marker with study drugs response, including efficacy and/or adverse events.
Measured: 44 months
DNA damage repair analysis
Evaluation of DNA damage repair (DDR) alterations on biopsy and blood samples collected before, during and after the treatment. It will be investigated the association of this marker with study drugs response, including efficacy and/or adverse events.
Measured: 44 months
Tumor Mutational Burden analysis
Evaluation of Tumor Mutational Burden (TMB) on biopsy and blood samples collected before, during and after the treatment. It will be investigated the association of this marker with study drugs response, including efficacy and/or adverse events.
Measured: 44 months
MicroSatellite Instability analysis
Evaluation of MicroSatellite Instability (MSI) on biopsy and blood samples collected before, during and after the treatment. It will be investigated the association of this marker with study drugs response, including efficacy and/or adverse events.
Measured: 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2022
- Study start27 Mar 2023
- Primary completionJul 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SCLC,Extensive StageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Angelo Delmonte, Study chair, IRCCS IRST
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05623319
- Sponsor's protocol ID
- IRST162.14
- Acronym
- THOR
- Status last verified
- Jun 2025
- First submitted
- 31 Oct 2022
- Last updated
- 24 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Translational Approach to First Line cHemoimmunotherapy Followed by Maintenance With pembrOlizumab and Olaparib in Extensive-Stage Small-Cell Lung CanceR.
- ClinicalTrials.gov ID
- NCT05623319
- Acronym / sponsor ID
- THOR / IRST162.14
- Conditions
- SCLC,Extensive Stage
- Keywords
- SCLC,Extensive Stage, Translational, Liquid Biopsy, Pembrolizumab, Olaparib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 27 Mar 2023 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 21 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
SCLC is a very aggressive disease with an overall survival (OS) of 12 months in the extensive stage (ES). Platinum-based as the first line of treatment has an overall response rate (ORR) of approximately 70% with a progression-free survival (PFS) of 5.5 months and an OS of almost 10 months. Prophylactic cranial irradiation, performed in order to prevent progression in brain, one of the major sites of recurrence, was associated with an increase in median disease-free survival of 12.0-14.7 weeks and in median OS of 5.4-6.7 months with a 1-year survival rate of 27.1%. At recurrence few therapeutic options are available. In order to improve clinical results, several strategies are under evaluation. Given the strong activity shown in several settings, immunotherapy is studied both as a single agent and in combinations.
Pembrolizumab has shown as maintenance after chemotherapy a PFS of 6.9 months in Programmed Cell Death 1 Ligand 1 (PD-L1) positive patients and as a monotherapy in 2nd and further lines an ORR of 19.3%, with major responses in PD-L1 positive patients and 61% of responders lasting ≥18 months. Recently the addition to standard chemotherapy of atezolizumab in patients with untreated ES-SCLC has led to an improvement of 2 months in OS (12.3 in the combo arms vs. 10.3 months in the control arm) and a slight improvement in PFS (5.2 vs. 4.3 months, respectively), without new safety data. Similarly addition of durvalumab to standard chemotherapy has led to a 2.7 months OS improvement (13 in the combo arms vs. 10.3 months in the control arm) with a relevant improvement in ORR (79.5 vs 70.3% respectively), without any improvement in PFS. Finally pembrolizumab combined with chemotherapy has shown significant improvement in PFS (hazard ratio (HR), 0.75; 95% confidence interval (CI), 0.61-0.91) but not in OS. Finally, considering the role of DNA damage repair systems in the tumorigenesis of SCLC, Olaparib has been also evaluated together with durvalumab in pre-treated ES-SCLC obtaining a clinical benefit of 21.1% and confirmed responses or stable disease for ≥8 months. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Despite biologic knowledge is growing, no clinically relevant molecular features have been identified. Recent publications in fact have proposed a new classification of SCLC in 3 major subgroups according to the expression of the neuronal basic helix-loop-helix transcription factors achaete-scute homologue 1 (ASCL1), involved in the neuroendocrine characterization, and the neurogenic differentiation factor 1 (NEUROD1). The so-called "classic type" shows expression of ASCL1, the "variant type" expresses NEUROD1 and the third type is negative for both the two previous biomarkers. In terms of gene profiling these subgroups are distinct but without a clear prognostic and predictive role. No driver mutations have been found. Many pathways are under evaluations. In particular Poly(ADP-Ribose) Polymerase (PARP) protein levels are up - regulated in SCLC relative to other lung cancers. In particular, Poly(ADP-Ribose) Polymerase 1 (PARP1) has been found to be highly expressed at both the messenger RNA (mRNA) and protein levels in SCLC samples. Given these data the combination proposed (Induction Phase with platinum/etoposide/pembrolizumab followed by a Maintenance Phase with pembrolizumab/olaparib) may be a new therapeutic option to be explored for patients. Moreover the evaluation of molecular features performed before, during and after this treatment may produce new evidence for further clinical trials.
The primary objective of the study is to evaluate the efficacy of chemo-immunotherapy induction followed by maintenance with pembrolizumab and olaparib in terms of Progression-free Survival (PFS).
Patients with extensive stage (ES) SCLC will receive pembrolizumab 200 mg 1q21 with 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.
Patients will be accrued for a period of 24 months and follow-up will continue for a period of 12 months after the last patient is enrolled.
The Kaplan-Meier approach will be used to estimate PFS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab/Olaparib | Experimental | Drug: Pembrolizumab/OlaparibPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (32 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab/OlaparibPatients 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. | Drug | Pembrolizumab/Olaparib |
Primary outcome
Progression free survival (PFS)
Time frame: 44 months
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.
9 secondary outcomes
Objective response rate (ORR)
Time frame: 36 months
Immune-related Objective response rate (irORR).
Time frame: 36 months
Progression free survival (PFS) at 6, 12, and 24 months
Time frame: About at 6-12-24 months
Overall Survival (OS)
Time frame: 44 months
Number of participants experiencing Adverse Events (AEs).
Time frame: 44 months
PD-L1 analysis
Time frame: 44 months
DNA damage repair analysis
Time frame: 44 months
Tumor Mutational Burden analysis
Time frame: 44 months
MicroSatellite Instability analysis
Time frame: 44 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Angelo Delmonte study chair
IRCCS IRST
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab/Olaparib in people with SCLC,Extensive Stage, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 12 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Oriana Nanni (+390543739266, oriana.nanni@irst.emr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: 44 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2025.