Efficacy and Safety Study of Pembrolizumab (MK-3475) in Participants With Advanced Recurrent Ovarian Cancer (MK-3475-100/KEYNOTE-100)

NCT02674061 | Completed Phase 2 Results

• 5 other identifiers: 3475-1002015-003338-29163237MK-3475-100KEYNOTE-100
• Study Type: interventional
• Target: 376
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assess the efficacy and safety of pembrolizumab (MK-3475) monotherapy in female participants with recurrent ovarian cancer (ROC) who have received up to 5 prior lines of treatment including platinum-based treatment for ROC (1 to 6 total prior lines counting front line therapy). Participants will be enrolled into two separate cohorts based on the number of prior lines of treatment received for ROC. There will be no hypothesis testing in this study.

Conditions

Ovarian Neoplasms

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Cohort A and Cohort B Participants

  ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters \[SOD\] of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported for all participants in Cohort A and Cohort B.

  Up to ~43 months (through database cut-off date of 18-September-2019)

• ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With Programmed Cell Death Ligand -1 (PD-L1) Combined Positive Score (CPS) ≥10

  ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported here as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥10.

  Up to ~43 months (through database cut-off date of 18-September-2019)

• ORR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

  ORR was defined as the percentage of participants in the analysis population who had a CR (Disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) using RECIST 1.1 based on BICR. ORR was analyzed by test of binomial parameter. The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported here as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥1.

  Up to ~43 months (through database cut-off date of 18-September-2019)

Secondary Outcomes (90)

• Duration of Response (DOR) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

  Up to ~43 months (through database cut-off date of 18-September-2019)

• DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

  Up to ~43 months (through database cut-off date of 18-September-2019)

• DOR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥1

  Up to ~43 months (through database cut-off date of 18-September-2019)

• Disease Control Rate (DCR) Per RECIST 1.1 by BICR in All Cohort A and Cohort B Participants

  Up to ~43 months (through database cut-off date of 18-September-2019)

• DCR Per RECIST 1.1 by BICR in Subgroup of Cohort A and Cohort B Participants With PD-L1 CPS ≥10

  Up to ~43 months (through database cut-off date of 18-September-2019)

Study Arms (2)

Cohort A: Pembrolizumab

EXPERIMENTAL

Participants in Cohort A received 0-2 prior lines of treatment for recurrent ovarian cancer (ROC; 1-3 total prior lines including front-line treatment) and will be administered pembrolizumab at a dose of 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to \~1 additional year).

Biological: Pembrolizumab

Cohort B: Pembrolizumab

EXPERIMENTAL

Participants in Cohort B received 3-5 prior lines of treatment for ROC (4-6 total prior lines including front-line treatment) and will be administered pembrolizumab at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to \~2 years). Qualified participants who complete 35 administrations of pembrolizumab but progress after discontinuation can initiate a second course of pembrolizumab 200 mg for up to 17 cycles (up to \~1 additional year)

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Administered at a dose of 200 mg via IV infusion on Day 1 of each 21-day cycle

Also known as: MK-3475, KEYTRUDA®

Cohort A: Pembrolizumab; Cohort B: Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Has histologically confirmed epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer
• Has received a front line platinum-based regimen (administered via either intravenous or intraperitoneal route) per local standard of care or treatment guideline following the primary or interval debulking surgery with documented disease recurrence (note: Maintenance treatment following the front line treatment is permitted and counted together as part of the front line treatment)
• Has fulfilled the following additional requirements regarding prior treatments for ROC depending on the cohort participant is to be enrolled. Each participant must have documented evidence of clinical response or disease stabilization to the last regimen received.
• Cohort A: Has received 0 to 2 additional prior lines for treating ROC (or 1-3 total prior lines counting the front line) and must have a platinum-free interval (PFI) of ≥ 3 to 12 months if the last regimen received is a platinum-based, or a treatment-free interval (TFI) of ≥ 3 to 12 months if the last regimen received is a non-platinum-based
• Cohort B: Has received 3 to 5 additional prior lines for treating ROC (or 4-6 total prior lines counting the front line) and must have a PFI of ≥ 3 months if the last regimen received is a platinum-based, or a TFI of ≥ 3 months if the last regimen received is a non-platinum-based
• Has measurable disease at baseline based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the central imaging vendor
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has a life expectancy of ≥16 weeks
• Has provided a tumor tissue sample either collected from prior cytoreductive surgery or fresh newly obtained tumor tissue at screening
• Has adequate organ function
• Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug

You may not qualify if:

• Is currently participating in or has participated in a clinical study and received an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., 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 diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study
• Has had prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to the planned first dose of the study
• Has not recovered from AEs to ≤ Grade 1 or prior treatment level due to a previously administered agent
• Has epithelial ovarian cancer (EOC) with mucinous histology subtype
• Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has symptoms of bowel obstruction in the past 3 months
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug
• Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen-4 \[CTLA-4\], tumor necrosis factor receptors OX-40 or CD137) or has participated in prior pembrolizumab (MK-3475) studies
• Has a known history of Human Immunodeficiency Virus (HIV)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, Raspagliesi F, Sonke GS, Birrer M, Provencher DM, Sehouli J, Colombo N, Gonzalez-Martin A, Oaknin A, Ottevanger PB, Rudaitis V, Katchar K, Wu H, Keefe S, Ruman J, Ledermann JA. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol. 2019 Jul 1;30(7):1080-1087. doi: 10.1093/annonc/mdz135.

  PMID: 31046082 RESULT

• Ledermann JA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, Raspagliesi F, Sonke GS, Birrer M, Provencher DM, Sehouli J, Colombo N, Gonzalez-Martin A, Oaknin A, Ottevanger PB, Rudaitis V, Kobie J, Nebozhyn M, Edmondson M, Sun Y, Cristescu R, Jelinic P, Keefe SM, Matulonis UA. Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100. Gynecol Oncol. 2023 Nov;178:119-129. doi: 10.1016/j.ygyno.2023.09.012. Epub 2023 Oct 18.

  PMID: 37862791 DERIVED

• Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.

  PMID: 35101941 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Ovarian Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: February 4, 2016
• Study Start: February 25, 2016
• Primary Completion: September 18, 2019
• Study Completion: March 18, 2021
• Last Updated: March 24, 2022
• Results First Posted: September 22, 2020

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share