Study of Pembrolizumab Following Surgery in Patients With Microsatellite Instability High (MSI-H) Solid Tumors

NCT03832569 | Active Not Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 18-399
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety of the study drug, pembrolizumab, and to find out how well it works to prevent cancer from coming back in people who have had a solid tumor surgically removed, but still have tumor cells in their blood. During the study, the participant will receive either the study drug or a placebo for as long as 12 months, or until the cancer comes back, or the side effects of the treatment become too severe.

Conditions

Solid Tumors; Identified by NGS, PCR or IHC

Keywords

Pembrolizumab; 18-399

Outcome Measures

Primary Outcomes (1)

• proportion of patients with ctDNA clearance

  Patients who have ctDNA clearance at 12 months will be considered responders, and patients who do not have ctDNA clearance at 12 months will be considered non-responders.

  12 months post randomization

Secondary Outcomes (1)

• disease free survival (DFS)

  5 years

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab 200 mg IV every 3 weeks over 30 minutes.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg IV every 3 weeks over 30 minutes.

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older
• ECOG performance status 0-1
• Any solid tumor with MSI or MRD by IHC, PCR or NGS testing. MSKCC confirmation of MSI-H/MRD status is not mandatory prior to enrollment and treatment on the study. For patients with outside testing, if sufficient tissue is available NGS will be repeated at MSKCC and will not impact the patient's eligibility.
• Must have genetic testing of DNA from primary tumor for somatic genomic alterations across a minimum of 50 genes.
• Must have undergone a complete curative surgical resection (R0)
• Must have completed standard of care (SOC) surgery, neoadjuvant or adjuvant therapy
• To be eligible for pembrolizumab or placebo therapy, the patients must have positive ctDNA (as defined in section 7.0) within 4 months after completion of appropriate standard of care therapy (surgery, chemotherapy, radiation as appropriate). Note, if ctDNA has a negative result, ctDNA can be re-tested up to 3 months later, within 9 months of completion of standard therapy.
• Patients must sign informed consent within 4 weeks of positive ctDNA result. The 4 weeks is considered from the date that the ctDNA is resulted, and not the date it is drawn.
• Demonstrate adequate organ function:
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL
• Serum creatinine ≤1.5 X upper limit of normal (ULN)
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN. Except patients with Gilbert's disease (≤3x ULN)
• AST and ALT ≤ 2.5 X ULN

You may not qualify if:

• Patients who have not recovered from serious adverse events (as determined by treating MD) related to surgery.
• Presence of metastatic or recurrent disease.
• Had R1 ( microscopic residual tumor) or R2 resection (macroscopic residual tumor at resection margin).
• 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.
• Has 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.
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled.
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• 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.
• o Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (2)

• Cowzer D, Janjigian YY. Top advances in esophageal/gastroesophageal junction cancers in 2021. Cancer. 2022 May 15;128(10):1894-1899. doi: 10.1002/cncr.34140. Epub 2022 Feb 18. No abstract available.

  PMID: 35179774 DERIVED

• Mendonca Gorgulho C, Krishnamurthy A, Lanzi A, Galon J, Housseau F, Kaneno R, Lotze MT. Gutting it Out: Developing Effective Immunotherapies for Patients With Colorectal Cancer. J Immunother. 2021 Feb-Mar 01;44(2):49-62. doi: 10.1097/CJI.0000000000000357.

  PMID: 33416261 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Pathologic Complete Response

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yelena Janjigian, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind study of adjuvant pembrolizumab or placebo in patients with MSI-H solid tumors with persistent circulating tumor DNA (ctDNA) despite curative surgery and completion of standard perioperative and/or adjuvant therapy

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 6, 2019
• Study Start: February 20, 2019
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR

Locations

US (7)