Ended Therapeutic exploratory (Phase II) Undifferentiated pleomorphic sarcoma and Dedifferentiated liposarcoma

A Window of Opportunity (WoO) study evaluating pembrolizumab with or without olaparib in Tertiary Lymphoid Structures (TLS)-positive selected resectable Soft Tissue Sarcoma (STS) followed by adjuvant pembrolizumab

EU CTIS ID: 2024-513469-38-00

What this study is testing

To evaluate the immunogenic potential of pembrolizumab +/- olaparib in WoO setting, in selected TLS+ selected STS subtypes. The WoO is the Windows of Opportunity, before standard surgery

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

Male or female patients aged ≥ 18 years at time of informed consent signature
Hepatitis B and C, and HIV screening tests are not required unless a. Known history of HBV, HCV or HIV infection b. As mandated by local health authority
10.1. Hepatitis B positive subjects a. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. b. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
10.2. Patients with history of HCV infection are eligible if HCV viral load is undetectable at screening a. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
10.3. Patients with history of HIV infection are eligible if HIV viral load is undetectable at screening a. Participants who are HIV positive are eligible if they have received HIV antiviral therapy for at least 4 weeks and have undetectable HIV viral load prior to randomization. b. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HIV anti-viral therapy post completion of study intervention.
A female participant is eligible to participate if she is not pregnant (see Appendix 3 – Contraceptive Guidance and Pregnancy Testing, i.e. negative pregnancy test 72 hours prior to first dose), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 to 180 days (corresponding to time needed to eliminate any study treatment(s) plus the duration of a menstruation cycle:120 days for pembrolizumab and/or 180 for olaparib) after the last dose of study treatment. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 – Contraceptive Guidance and Pregnancy Testing of this protocol during the treatment period and for at least 180 to 240 days, corresponding to time needed to eliminate any study treatment(s) plus the duration of a spermatogenesis cycle: 180 days for pembrolizumab and/or 240 days for olaparib) after the last dose of study treatment and refrain from donating sperm during this period.

You likely can't join if

Has a visceral STS primary site.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has had an administration of colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to Cycle 0 Day 1.
A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization (see Appendix 3 – Contraceptive Guidance and Pregnancy Testing). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
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 a history of severe allergic, anaphylactic, or other hypersensitivity reactions to the components of excipients in pembrolizumab and/or olaparib.

See the full eligibility criteria

Who can join

Male or female patients aged ≥ 18 years at time of informed consent signature
Hepatitis B and C, and HIV screening tests are not required unless a. Known history of HBV, HCV or HIV infection b. As mandated by local health authority
10.1. Hepatitis B positive subjects a. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. b. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
10.2. Patients with history of HCV infection are eligible if HCV viral load is undetectable at screening a. Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
10.3. Patients with history of HIV infection are eligible if HIV viral load is undetectable at screening a. Participants who are HIV positive are eligible if they have received HIV antiviral therapy for at least 4 weeks and have undetectable HIV viral load prior to randomization. b. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HIV anti-viral therapy post completion of study intervention.
A female participant is eligible to participate if she is not pregnant (see Appendix 3 – Contraceptive Guidance and Pregnancy Testing, i.e. negative pregnancy test 72 hours prior to first dose), not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 to 180 days (corresponding to time needed to eliminate any study treatment(s) plus the duration of a menstruation cycle:120 days for pembrolizumab and/or 180 for olaparib) after the last dose of study treatment. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 – Contraceptive Guidance and Pregnancy Testing of this protocol during the treatment period and for at least 180 to 240 days, corresponding to time needed to eliminate any study treatment(s) plus the duration of a spermatogenesis cycle: 180 days for pembrolizumab and/or 240 days for olaparib) after the last dose of study treatment and refrain from donating sperm during this period.
Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
Patient should be able and willing to comply with baseline mandatory biopsy, as well as study visits and procedures as per protocol.
Patients must be affiliated to a social security system or beneficiary of an equivalent system.
Histologically confirmed diagnosis of high grade (FNCLCC grade 2 or 3) extremity, retroperitoneal, or trunk wall STS of selected histotypes as defined below. Diagnosis must be stated in a pathology report and confirmed by the physician investigator: • Cohort 1: Undifferentiated Pleomorphic Sarcoma (UPS) • Cohort 2: Dedifferentiated Liposarcoma (ddLPS)
R0 resectability at time of enrollment according to expert STS surgeon and absence of indication of pre-operative chemotherapy according to best practice guidelines, or previous administration of preoperative therapy
Absence of distant metastasis on screening CT-scan (or equivalent appropriate imaging technique)
Patients with local relapse after an initial surgical resection can be enrolled if no perioperative chemotherapy or radiation has been previously performed
Identification of Tertiary Lymphoid Structures (TLSs) on tumor archival FFPE sample, as assessed by a registered STS expert senior pathologist
Primary tumor site measurable according to RECIST v1.1 as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and suitable for repeated assessment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration from registration date
Adequate hematologic and organ function, defined by the following laboratory results obtained within 3 days prior to the first study treatment (Table 2):

What rules you out

Has a visceral STS primary site.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has had an administration of colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to Cycle 0 Day 1.
A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization (see Appendix 3 – Contraceptive Guidance and Pregnancy Testing). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
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 a history of severe allergic, anaphylactic, or other hypersensitivity reactions to the components of excipients in pembrolizumab and/or olaparib.
Has any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) or immunodeficiency
Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g.., thyroxine, insulin, or physiologic corticosteroid)
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has a history of allogeneic tissue/organ or hematopoietic stem cell transplantation.
Has a history of another primary malignancy within 2 years prior to Cycle 0 Day 1 except for: • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease • Adequately treated carcinoma in situ without evidence of disease (e.g., carcinoma in situ of the cervix, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent, carcinoma in situ of the bladder that have undergone potentially curative therapy)
Has a non resectable or marginally resectable locally advanced STS as assessed by expert STS surgeon.
Has a serious, uncontrolled medical disorder including, but not limited to: • Ongoing or active infection or severe infection requiring hospitalization or IV antibiotics within 2 weeks of starting treatment (with the exception of prophylactic antibiotics) • Any of the following cardiac conditions: o Symptomatic uncontrolled congestive heart failure > NYHA II o Left ventricular ejection fraction (LVEF) < 40%; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable cardiologic treatment. o Presence of uncontrolled, potentially reversible cardiac conditions: uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, pericardial effusion, myocardial infarction within 90 days o QTcF prolongation >500 ms, or participant has congenital long QT syndrome • Active peptic ulcer disease or gastritis • Active bleeding diatheses • Major seizure disorder • Extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan
Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA), Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection, HIV (defined as detectable viral load). Note: HIV, Hepatitis B and C screening tests are not required unless: • Known history of HBV, HCV or HIV infection • As mandated by local health authority
Has any active infection requiring systemic therapy.
Major surgical procedure within 20 days prior ty Cycle 0 Day 1 or anticipation of need for a major surgical procedure during the course of the study.
Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant 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.
Participant is currently receiving either strong (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks. The medication can be restarted as soon as olaparib has been halted.
Participant is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate (e.g., bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents. The medication can be restarted as soon as olaparib has been halted.
Has evidence of metastatic disease on CT-scan (or equivalent imaging technique).
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization.
Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.
Has had previous exposure to anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another stimulatory or co inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
Had had previous exposure to olaparib or any other PARP inhibitor.
Has received a live vaccine or live-attenuated vaccine received within 4 weeks prior to Cycle 0 Day 1 or anticipation that such a live attenuated vaccine will be required during the study. Administration of killed vaccines is allowed.
Has received treatment with systemic immunostimulatory agents (e.g., IFN and IL-2) within 4 weeks prior to Cycle 0 Day 1.

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.