Phase II Study of Pembrolizumab with Chemotherapy in Platinum-Sensitive Recurrent Low-Grade Serous Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Trial ID: 2023-508155-40-00
Protocol: NOGGO-ov44
Sponsor: Nord-Ostdeutsche Gesellschaft Fuer Gynaekologische Onkologie e.V.

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Diseases & Conditions

Fallopian tube cancer Ovarian cancer recurrent Peritoneal cancer index

Objectives

The primary objective of this Phase II investigational study is to evaluate the **progression-free survival** rate at 12 months following the initiation of treatment with pembrolizumab in combination with chemotherapy in patients with recurrent platinum-sensitive low-grade serous ovarian cancer. This objective is clinically relevant as it aims to determine the efficacy of pembrolizumab in prolonging the time patients remain free from disease progression, which is a critical measure of treatment success in oncology. No secondary objectives are specified for this study.

Participants

The clinical trial focuses on evaluating the efficacy of pembrolizumab in patients with **recurrent platinum-sensitive low-grade serous ovarian cancer**, fallopian tube cancer, and/or primary peritoneal cancer. The study population consists exclusively of female participants aged 18 years and older. Participants are required to have a histological diagnosis of the specified cancer types and must have completed at least one previous course of platinum-containing therapy. The trial does not include male subjects or vulnerable populations. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial requires participants to have adequate organ and bone marrow function. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy of **pembrolizumab** in combination with chemotherapy for patients with recurrent platinum-sensitive low-grade serous ovarian cancer. This is a Phase II, randomized, double-blind, controlled study. The primary objective is to assess the progression-free survival rate 12 months after the start of treatment. The trial is expected to conclude by December 31, 2028, with recruitment having commenced on February 22, 2022. Participants will be involved in the study for a maximum treatment period of 105 weeks, with the possibility of early termination if specific conditions arise, such as adverse reactions or disease progression.

The study involves a sequence of visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and previous treatment history. Participants must have completed at least one course of platinum-containing therapy and exhibit platinum-sensitive disease. The screening visit will also include a pregnancy test for women of childbearing potential and the collection of tumor tissue samples. Following the inclusion visit, participants will undergo regular follow-up visits to monitor treatment response and safety, with assessments of progression-free survival, overall response rate, and quality of life. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination, where final evaluations will be conducted.

Secondary endpoints include overall response rate, overall survival, and progression-free survival at various intervals (6, 12, 18, and 24 months), as well as safety assessments using CTCAE v5.0. Participants will receive the study drug via intravenous administration, with a maximum daily dose of 200 mg. The trial will adhere to strict eligibility criteria, including adequate organ and bone marrow function, and participants must provide written informed consent. The study aims to provide valuable insights into the efficacy and safety of pembrolizumab in this patient population, contributing to the advancement of treatment options for low-grade serous ovarian cancer.

Treatment

The clinical trial involves the administration of **pembrolizumab**, marketed under the name **KEYTRUDA**. This investigational medication is provided as a **25 mg/mL concentrate for solution for infusion**. The pharmaceutical form is a **solution for infusion**, and it is administered via **intravenous administration**. The maximum daily dose is 200 mg, with the same amount being the maximum total dose per administration. The treatment period is set for a maximum of 105 days. **Pembrolizumab** is a protein-based therapeutic agent, specifically classified under the ATC code L01FF02. It is produced by Merck Sharp & Dohme B.V. and is not designated as an orphan drug or a pediatric formulation.

In this study, **pembrolizumab** is being evaluated in combination with chemotherapy for patients with platinum-sensitive recurrent low-grade serous ovarian cancer. The primary objective is to assess the progression-free survival rate 12 months after the initiation of treatment. No additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial documentation. Compliance with the dosing schedule and administration is monitored throughout the study to ensure adherence to the protocol.

Efficacy

Efficacy in this clinical trial will be assessed primarily through the measurement of the **progression-free survival (PFS)** rate at 12 months following the initiation of treatment. This endpoint is designed to evaluate the effectiveness of pembrolizumab in combination with chemotherapy in patients with low-grade serous ovarian cancer. Secondary endpoints include overall response rate (ORR), overall survival (OS), and PFS rates at 6, 12, 18, and 24 months. Additionally, the trial will assess PFS and OS as time-to-event variables, response rates categorized as stable disease (SD), partial response (PR), or complete response (CR) at specified intervals, and the expression of Ki-67 in relation to response rate and PFS.

Safety endpoints will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to determine the safety of the combination therapy. Other parameters include the time to first subsequent treatment (TFST) and response to first subsequent treatment, as well as quality of life assessments using the EORTC-QLQ-C30 and EORTC-QLQ-OV-28 instruments, which will be conducted until 6 months after disease progression. The trial is structured to collect and analyze these efficacy parameters at multiple timepoints, ensuring a comprehensive evaluation of the treatment's impact on disease progression and patient outcomes.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Female, age at least 18 years.
Histologically diagnosed low-grade serous ovarian-, fallopian tube- and/or primary peritoneal cancer.
Patients must have completed at least 1 previous course of platinum-containing therapy (e.g., combination with carboplatin or cisplatin. Maintenance therapy with bevacizumab and/or endocrine agents (e.g. letrozole) is allowed. Neoadjuvant chemotherapy in the first line therapy will be counted as one line of therapy. Patients may, but are not required to, have a previous cytoreductive surgery in the first as well as in the second line.
Patients must have platinum sensitive disease, e.g. progression or recurrence after platinum-containing therapy, occurring no sooner than 6 months after completion of the last dose of platinum chemotherapy.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Women of childbearing potential should not become pregnant while on the study therapy and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to receiving the study therapy. Women of childbearing potential must agree to follow contraceptive guidance in Appendix 3 of the protocol during the treatment period and for 6 months after receiving the last dose of the study therapy.
The participant provides written informed consent for the trial.
Availability of archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
Have adequate organ and bone marrow function as defined in Table 1 of the study protocol.

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Exclusion Criteria

High-grade ovarian cancer or other than low grade serous ovarian cancer ovarian malignancy.
Persistent ≥Grade 2 non-hematologic toxicity from prior cancer therapy
Has received prior therapy with an anti-PD-1, anti-PD-L1, or 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).
Is eligible for carboplatin-based doublet therapy in combination with bevacizumab in the relapse situation, since no treatment with bevacizumab has been administered in the first line therapy.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (time between last antineoplastic therapy and start of study therapy should be at least 4 weeks).
Has received prior radiotherapy within 2 weeks of start of study treatment. 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.
Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
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 a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Has known active 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 treatment.
Has a bleeding tumor
Has hypersensitivity to any of the study drugs the patient will be treated with and/or to any of the excipients of the study drugs the patient will be treated with.
Has hypersensitivity to platin-containing compounds other than carboplatin.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Has active infection with SARS-CoV-2 (antigen test).
Has a history of Human Immunodeficiency Virus (HIV) infection (known HIV1/HIV2 antibodies positive, mandatory testing for HIV during screening is required).
Has a history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or active Hepatitis C virus (defined as HCV RNA [qualitative] has been detected) infection (mandatory testing for Hepatitis B and Hepatitis C during screening is required).
Has a known history of active TB (Bacillus Tuberculosis).
Has a 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 had an allogenic tissue/ solid organ transplant.
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 within the projected duration of the study, starting with the screening visit through 6 months after the last dose of trial treatment
Patients unable to be regularly followed for any reason (geographic, familiar, social, psychologic, housed in an institution e.g. prison because of a court agreement or administrative order according to § 40 Abs. 1 S. 3 Nr. 4 AMG).
Subjects that are depending on the sponsor/CRO or investigational site as well as on the investigator.