Study Evaluating Pembrolizumab +/- Olaparib in TLS Positive Selected Resectable STS Followed by Adjuvant Pembrolizumab

NCT06116578 | Withdrawn Phase 2 DMC

• 2 other identifiers: 2024-513469-38-002023/3610
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Soft tissue sarcomas represent a subtype of cancer that is both rare and very heterogeneous. When they are organized, their current treatment is essentially based on tumor resection surgery, +/- associated with treatment by chemotherapy and/or radiotherapy. The aim of this treatment is to reduce the risk of local recurrence (appearance of a tumor in the same region where it was first detected) and/or distant (appearance of a tumor in other regions, organs where it was first detected). Currently, no immunotherapy treatment has been approved for the treatment of patients with sarcoma. This research is based on the hypothesis that soft tissue sarcomas in which "tertiary lymphoid structures" or "TLS" are found, recognizable by a cluster of specific immune cells within the tumor, would be likely to respond better to the immunotherapy. Furthermore, the combination of immunotherapy and certain drugs targeting DNA repair has demonstrated some effectiveness in other types of cancers. Trial population :Adult patients with suspected / diagnosed soft tissue sarcoma of the extremities or trunk (Cohort 1: Undifferentiated pleomorphic sarcoma / Cohort 2: Dedifferentiated liposarcoma) The research will therefore focus on two experimental drugs :

• Pembrolizumab (immunotherapy) and
• Olaparib (DNA repair inhibitor). This research will make it possible to evaluate the effectiveness and safety of use of the two drugs.

Conditions

Cancer

Keywords

sarcoma; TLS; Liposarcoma; immunotherapy; PARP

Outcome Measures

Primary Outcomes (1)

• Rate of CD8+ T-cell tumor infiltration density at surgery compare to baseline

  50% increase in CD8+ T-cell tumor infiltration density between baseline biopsy and resection surgery specimen as defined by expert pathologist who will be blinded for treatment arm and patient outcome

  1 year after the end of inclusions

Secondary Outcomes (10)

• Proportion of patients with 70% pathological response

  Through study completion, an average of 1 year

• Surgery evaluation: Quality of resection as defined by Hemanek and Wittekind (R0 the best / R1 / R2 the worst)

  Through study completion, an average of 1 year

• Surgery evaluation : amputation rate

  Through study completion, an average of 1 year

• Surgery evaluation : Incidence of acute wound complications up to 120 days after surgery

  120 days after surgery

• Objective Response Rate (ORR)

  At 4 weeks of WoO treatment

Study Arms (2)

A: Pembrolizumab before surgery

ACTIVE COMPARATOR

Before surgery: Pembrolizumab 200 mg two intravenous (IV) infusions q3w (2 injections: at C1D1 and C1D21)

Drug: Pembrolizumab; Drug: Pembrolizumab adjuvant

B: Pembrolizumab + olaparib before surgery

ACTIVE COMPARATOR

Before surgery: Pembrolizumab 200 mg two IV infusions q3w (2 injections: at C1D1 and C1D21) + concomitant full dose olaparib (300 mg per os b.i.d) during four weeks

Drug: Pembrolizumab and Olaparib; Drug: Pembrolizumab adjuvant

Interventions

Pembrolizumab DRUG

cf Arm A

Also known as: WOO (Windows of opportunity)

A: Pembrolizumab before surgery

Pembrolizumab and Olaparib DRUG

cf Arm B

Also known as: WOO (Windows of opportunity)

B: Pembrolizumab + olaparib before surgery

Pembrolizumab adjuvant DRUG

After surgery (adjuvant phase), all patients (Arm A and B) will receive pembrolizumab 200 mg two intravenous (IV) infusions q3w for one-year

Also known as: Adjuvant

A: Pembrolizumab before surgery; B: Pembrolizumab + olaparib before surgery

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥ 18 years at time of informed consent signature
• 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
• 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 (Cycle 0 Day 1): Absolute neutrophil count (ANC) ≥ 1500 cells/μL, Platelet count ≥ 100.000/μL, Hemoglobin ≥ 10 g/dL, Total bilirubin ≤ 1.5 ULN (subjects with documented/suspected Gilbert's disease may be enrolled with bilirubin ≤ 3 × ULN), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit (ULN), Albumin ≥ 28g/L, Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min (according to Cockcroft and Gault formula), International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on stable dose.
• Hepatitis B and C, and HIV screening tests are not required unless
• Known history of HBV, HCV or HIV infection
• As mandated by local health authority
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for 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 days for olaparib) after the last dose of study treatment.

You may not qualify if:

• Has a visceral STS primary site.
• Has a non-resectable or marginally resectable locally advanced STS, as assessed by expert STS surgeon.
• 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.
• 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

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94800, France

Location

MeSH Terms

Conditions

Neoplasms; Sarcoma; Liposarcoma

Interventions

pembrolizumab; olaparib; Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Adipose Tissue

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Design

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

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: November 3, 2023
• Study Start: January 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)