Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

Feasibility Study of Neo-adjuvant Treatment With Carboplatin, Paclitaxel and Pembrolizumab in Primary Stage IV Serous Ovarian Cancer

This is a single arm feasibility study in patients with primary FIGO stage IV serous ovarian, peritoneal, or fallopian tube cancer to evaluate neo-adjuvant + adjuvant pembrolizumab for its capacity to induce and broaden T cell responses against tumor neo-antigens.

Study Overview

• Status: Completed
• Conditions: Fallopian Tube Cancer; Peritoneal Cancer; Ovarian Cancer Stage IV
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Drug: Pembrolizumab

Detailed Description

Long-term survival in stage IV serous ovarian, peritoneal, and fallopian tube cancer is poor and has not significantly improved over the last decades. Standard treatment consists of debulking surgery and six courses of carboplatin and paclitaxel. Nevertheless, the disease recurs in >90% of women, usually within two years.

Since early observations that the presence of infiltrating T cells is associated with improved outcome, ovarian cancer is linked to a potential benefit of immunotherapy.10 More recently, T cell checkpoint blockade with anti-PD1 and anti-PDL1 have shown promising activity in platinum resistant ovarian cancer with objective and durable responses in 10-20% of patients. This finding raises the question whether anti-PD1 could also play a role in first line treatment of ovarian cancer.

To fully use the power of T cell checkpoint inhibition, sufficient TCR stimulation is required. Importantly, the amount of antigen that can provide this signal will correlate with tumor load, and because of this adjuvant immunotherapy may work most efficiently, when initiated prior to surgery. In addition, we postulate that antigen retrieval will increase after induction treatment with cytotoxic therapy.

To address these questions, we propose a feasibility study in patients with FIGO stage IV serous ovarian, peritoneal, or fallopian tube cancer in which we evaluate pembrolizumab added to standard treatment for its capacity to induce and broaden T cell responses against neo-antigens.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Antoni van Leeuwenhoek

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent for the trial.
• Diagnosis of primary stage IV high-grade serous ovarian, peritoneal, or fallopian tube cancer.
• Age >= 18 years on day of signing informed consent.
• Willing and able to provide three tumor biopsies (1 FFPE, 2 fresh frozen) prior to start of treatment
• Performance status of 0 or 1 on the ECOG Performance Scale.
• Adequate organ function as defined in Table 1 of the protocol
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria:

• Previously received treatment for ovarian, peritoneal, or fallopian tube cancer.

  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Known additional malignancy, unless treated with curative intent without chemotherapy at least five years ago. In situ cancers, basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have undergone potentially curative therapy within the past five years may also be eligible.
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• A known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carboplatin, paclitaxel, pembrolizumab; Carboplatin AUC= 6 paclitaxel 80 mg/m2 Pembrolizumab 200 mg starting cycle 2	Drug: Carboplatin; Carboplatin AUC=6; Drug: Paclitaxel; paclitaxel 80 mg/m2; Drug: Pembrolizumab; 200 mg flat dose, starting cycle 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of T-cells in peripheral blood	determine the number of T cells in peripheral blood samples and tissue samples	up to week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0	Toxicity will be analyzed in patients who have received at least one administration of pembrolizumab.	up to 30 days after end of treatment
Response Rate	number of patients with no viable invasive tumor left in the resection specimen	at week 12, debulking surgery
Response rate according to RECIST	Number of patients with partial or complete response according to RECIST	at week 3 and 6

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): March 5, 2024

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Neo adjuvant; Primary stage 4
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Paclitaxel; Pembrolizumab
• Other Study ID Numbers: N16OPE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: to be determinated

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No