Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28)

NCT02054806 | Completed Phase 1 Results

• 5 other identifiers: 3475-028142515MK-3475-028KEYNOTE-282013-004507-39
• Study Type: interventional
• Target: 477
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will assess the efficacy and safety of pembrolizumab (MK-3475) administered to participants with incurable advanced biomarker-positive solid tumors that have not responded to current therapy or for which current therapy is not appropriate. The study hypothesis is that administration of pembrolizumab to participants with some types of solid tumors will result in a clinically meaningful response rate.

Conditions

Solid Tumor

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate (ORR) was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator.

  Up to approximately 86 months

Secondary Outcomes (5)

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 28 months

• Number of Participants Who Discontinued From Study Treatment Due to an AE

  Up to approximately 25 months

• Progression Free Survival (PFS)

  Up to approximately 86 months

• Overall Survival (OS)

  Up to approximately 86 months

• Duration of Response (DOR)

  Up to approximately 86 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Participants receive pembrolizumab 10 mg/kg, intravenously (IV), once every 2 weeks (Q2W) for up to \~2 years

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented locally-advanced and/or metastatic solid malignancy that is incurable, and has failed prior standard therapy or for which standard therapy is not appropriate
• Have biomarker-positive solid tumor
• Have measurable disease based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
• 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 medication
• Male participants of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication

You may not qualify if:

• Is 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
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Prior anti-cancer therapy with a monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from adverse events due to mAbs administered more than 4 weeks earlier
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks (12 weeks for measurable sites of central nervous system \[CNS\] disease) prior to study Day 1 or not recovered from adverse events due to a previously administered agent
• Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
• Known active CNS metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in 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 evidence of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Active infection requiring systemic therapy
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-PD-1, anti-PD-L1, and anti-PD-L2 (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Known history of human immunodeficiency virus (HIV)
• Known active Hepatitis B or Hepatitis C
• Has received a live vaccine within 30 days of planned start of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (18)

• Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, van Brummelen E. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017 May;18(5):623-630. doi: 10.1016/S1470-2045(17)30169-9. Epub 2017 Mar 11.

  PMID: 28291584 RESULT

• Ott PA, Piha-Paul SA, Munster P, Pishvaian MJ, van Brummelen EMJ, Cohen RB, Gomez-Roca C, Ejadi S, Stein M, Chan E, Simonelli M, Morosky A, Saraf S, Emancipator K, Koshiji M, Bennouna J. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017 May 1;28(5):1036-1041. doi: 10.1093/annonc/mdx029.

  PMID: 28453692 RESULT

• Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24.

  PMID: 28837405 RESULT

• Ott PA, Elez E, Hiret S, Kim DW, Morosky A, Saraf S, Piperdi B, Mehnert JM. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829. doi: 10.1200/JCO.2017.72.5069. Epub 2017 Aug 16.

  PMID: 28813164 RESULT

• Doi T, Piha-Paul SA, Jalal SI, Saraf S, Lunceford J, Koshiji M, Bennouna J. Safety and Antitumor Activity of the Anti-Programmed Death-1 Antibody Pembrolizumab in Patients With Advanced Esophageal Carcinoma. J Clin Oncol. 2018 Jan 1;36(1):61-67. doi: 10.1200/JCO.2017.74.9846. Epub 2017 Nov 8.

  PMID: 29116900 RESULT

• Frenel JS, Le Tourneau C, O'Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, van Brummelen EMJ, Rugo HS, Thomas S, Saraf S, Rangwala R, Varga A. Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial. J Clin Oncol. 2017 Dec 20;35(36):4035-4041. doi: 10.1200/JCO.2017.74.5471. Epub 2017 Nov 2.

  PMID: 29095678 RESULT

• O'Neil BH, Wallmark JM, Lorente D, Elez E, Raimbourg J, Gomez-Roca C, Ejadi S, Piha-Paul SA, Stein MN, Abdul Razak AR, Dotti K, Santoro A, Cohen RB, Gould M, Saraf S, Stein K, Han SW. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. PLoS One. 2017 Dec 28;12(12):e0189848. doi: 10.1371/journal.pone.0189848. eCollection 2017.

  PMID: 29284010 RESULT

• Cohen RB, Delord JP, Doi T, Piha-Paul SA, Liu SV, Gilbert J, Algazi AP, Damian S, Hong RL, Le Tourneau C, Day D, Varga A, Elez E, Wallmark J, Saraf S, Thanigaimani P, Cheng J, Keam B. Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study. Am J Clin Oncol. 2018 Nov;41(11):1083-1088. doi: 10.1097/COC.0000000000000429.

  PMID: 29462123 RESULT

• Rugo HS, Delord JP, Im SA, Ott PA, Piha-Paul SA, Bedard PL, Sachdev J, Le Tourneau C, van Brummelen EMJ, Varga A, Salgado R, Loi S, Saraf S, Pietrangelo D, Karantza V, Tan AR. Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Clin Cancer Res. 2018 Jun 15;24(12):2804-2811. doi: 10.1158/1078-0432.CCR-17-3452. Epub 2018 Mar 20.

  PMID: 29559561 RESULT

• Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, Puzanov I, Mehnert JM, Aung KL, Lopez J, Carrigan M, Saraf S, Chen M, Soria JC. Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study. J Clin Oncol. 2017 Aug 1;35(22):2535-2541. doi: 10.1200/JCO.2017.72.5952. Epub 2017 May 10.

  PMID: 28489510 RESULT

• Varga A, Piha-Paul S, Ott PA, Mehnert JM, Berton-Rigaud D, Morosky A, Yang P, Ruman J, Matei D. Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Gynecol Oncol. 2019 Feb;152(2):243-250. doi: 10.1016/j.ygyno.2018.11.017. Epub 2018 Dec 3.

  PMID: 30522700 RESULT

• 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

• Reardon DA, Kim TM, Frenel JS, Simonelli M, Lopez J, Subramaniam DS, Siu LL, Wang H, Krishnan S, Stein K, Massard C. Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Cancer. 2021 May 15;127(10):1620-1629. doi: 10.1002/cncr.33378. Epub 2021 Jan 26.

  PMID: 33496357 DERIVED

• Piha-Paul SA, Oh DY, Ueno M, Malka D, Chung HC, Nagrial A, Kelley RK, Ros W, Italiano A, Nakagawa K, Rugo HS, de Braud F, Varga AI, Hansen A, Wang H, Krishnan S, Norwood KG, Doi T. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies. Int J Cancer. 2020 Oct 15;147(8):2190-2198. doi: 10.1002/ijc.33013. Epub 2020 May 2.

  PMID: 32359091 DERIVED

• Mehnert JM, Bergsland E, O'Neil BH, Santoro A, Schellens JHM, Cohen RB, Doi T, Ott PA, Pishvaian MJ, Puzanov I, Aung KL, Hsu C, Le Tourneau C, Hollebecque A, Elez E, Tamura K, Gould M, Yang P, Stein K, Piha-Paul SA. Pembrolizumab for the treatment of programmed death-ligand 1-positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study. Cancer. 2020 Jul 1;126(13):3021-3030. doi: 10.1002/cncr.32883. Epub 2020 Apr 22.

  PMID: 32320048 DERIVED

• Mehnert JM, Varga A, Brose MS, Aggarwal RR, Lin CC, Prawira A, de Braud F, Tamura K, Doi T, Piha-Paul SA, Gilbert J, Saraf S, Thanigaimani P, Cheng JD, Keam B. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced, PD-L1-positive papillary or follicular thyroid cancer. BMC Cancer. 2019 Mar 4;19(1):196. doi: 10.1186/s12885-019-5380-3.

  PMID: 30832606 DERIVED

• Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria JC, Rugo HS, Cohen RB, O'Neil BH, Mehnert JM, Lopez J, Doi T, van Brummelen EMJ, Cristescu R, Yang P, Emancipator K, Stein K, Ayers M, Joe AK, Lunceford JK. T-Cell-Inflamed Gene-Expression Profile, Programmed Death Ligand 1 Expression, and Tumor Mutational Burden Predict Efficacy in Patients Treated With Pembrolizumab Across 20 Cancers: KEYNOTE-028. J Clin Oncol. 2019 Feb 1;37(4):318-327. doi: 10.1200/JCO.2018.78.2276. Epub 2018 Dec 13.

  PMID: 30557521 DERIVED

• Hansen AR, Massard C, Ott PA, Haas NB, Lopez JS, Ejadi S, Wallmark JM, Keam B, Delord JP, Aggarwal R, Gould M, Yang P, Keefe SM, Piha-Paul SA. Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study. Ann Oncol. 2018 Aug 1;29(8):1807-1813. doi: 10.1093/annonc/mdy232.

  PMID: 29992241 DERIVED

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Results Point of Contact

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

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 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2014
• First Posted: February 4, 2014
• Study Start: February 17, 2014
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: October 30, 2023
• Results First Posted: October 30, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share