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Clinical Trial 21442

Cancer Type: Gynecological Tumor
Study Type: Treatment
NCT#: NCT05116189

Phase: Phase III
Principal Investigator: Wenham, Robert

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Overview

Study Title

A Phase 3, Randomized, Double-Blind Study of Pembrolizumab versus Placebo in Combination with Paclitaxel with or without Bevacizumab for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer

Summary

The primary objective is to compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator. The hypotheses are that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for participants with programmed cell death ligand 1 (PD-L1) positive tumors (Combined Positive Score [CPS] ≥1) and that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for all participants.

Objective

Primary Objectives: *To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by the investigator *Hypothesis (H1): pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for participants with programmed cell death ligand 1 (PD-L1) positive tumors (Combined Positive Score [CPS] ≥1) *Hypothesis (H2): pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for all participants Secondary Objectives: *To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to overall survival (OS) *Hypothesis (H3): Pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to OS for participants with PD-L1 positive tumors (CPS ≥1) *Hypothesis (H4): Pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to OS for all participants *To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 by blinded independent central review (BICR) for participants with PD-L1 positive tumors (CPS ≥1) and all participants *To evaluate the safety and tolerability of pembrolizumab in combination with paclitaxel with or without bevacizumab *To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to Global Health Status/Quality of Life (GHS/QoL) score using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and abdominal and gastrointestinal (GI) symptoms using the EORTC Ovarian Cancer-Specific Quality of Life Questionnaire (QLQ-OV28) abdominal/GI symptom scale for participants with PD-L1 positive tumors (CPS ≥1) and all participants Tertiary/Exploratory Objectives: *To evaluate the objective response rate (ORR) per RECIST 1.1 as assessed by the investigator, in participants with measurable disease per RECIST 1.1 at baseline, for participants with PD-L1 positive tumors (CPS ≥1) and all participants *To evaluate the time to first subsequent anticancer treatment (TFST), the time to second subsequent anticancer treatment (TSST), and the time to discontinuation of study treatment (TDT) for participants with PD-L1 positive tumors (CPS ≥1) and all participants *To evaluate the time without symptoms of disease progression or toxicity of treatment (TWiST) for participants with PD-L1 positive tumors (CPS ≥1) and all participants *To evaluate other health-related QoL scale scores of the EORTC QLQ-C30 and the EORTC QLQ-OV28 for participants with PD-L1 positive tumors (CPS ≥1) and all participants *To characterize health utilities using the European Quality of Life Five-dimension Five-level Scale Questionnaire (EuroQoL EQ-5D-5L) for participants with PD-L1 positive tumors (CPS ≥1) and all participants *To evaluate the PFS after next-line treatment (PFS2) after discontinuation of study intervention as determined by the investigator according to the local standard of practice for participants with PD-L1 positive tumors (CPS ≥1) and all participants *To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may be indicative of clinical response/resistance, safety, pharmacodynamic activity, and/or the mechanism of action of pembrolizumab and other treatments

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy

Medications

Avastin (Bevacizumab); Bevacizumab (); Diphenhydramine (); MK-3475 (Keytruda); Pembrolizumab (Keytruda); Taxol (paclitaxel); acetaminophen (); paclitaxel ()

Inclusion Criteria

  • Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
  • Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-PD-1/anti-PD-L1 therapy, bevacizumab, or hormonal therapy; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
  • Has provided documented informed consent for the study.
  • Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
  • Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
  • For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of > Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator.
  • Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
  • Have adequate organ function.

  • Exclusion Criteria

  • Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.
  • Has primary platinum-refractory disease, defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of first-line platinum-based therapy.
  • Has prior disease progression on weekly paclitaxel alone.
  • Has received >2 prior lines of systemic therapy for OC.
  • Has received prior systemic anticancer therapy including investigational agents or maintenance therapy (including bevacizumab maintenance therapy), within 4 weeks before randomization.
  • Has received prior radiation therapy within 2 weeks of start of study intervention.
  • Has not recovered adequately from surgery and/or any complications from the surgery.
  • Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant erythropoietin) within 4 weeks before randomization.
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
  • Has received investigational agent or has used an investigational device within 4 weeks prior to study intervention.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years.
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection.
  • Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study.
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
  • Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
  • Has had an allogenic tissue/solid organ transplant.
  • For bevacizumab treatment:
  • Has uncontrolled hypertension.
  • Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
  • Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.

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