Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer.

NCT03220477 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 17-241
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the safety of a combination of three drugs, pembrolizumab, guadecitabine and mocetinostat. Pembrolizumab is a drug given by vein and all patients will receive the same dose. Guadecitabine and mocetinostat will be given at different doses to find out what effects, if any, they have on treating your cancer and side effects.

Conditions

Lung Cancer

Keywords

Pembrolizumab; guadecitabine; mocetinostat; 17-241

Outcome Measures

Primary Outcomes (2)

• number of patients with adverse events

  events occurring on or after treatment on the first day of any study therapy will be summarized by dose cohort, toxicity term, CTCAE v4.0 grade

  1 year

• response rate (Phase Ib)

  Tumor response will be assessed using RECIST 1.1. All responses must be confirmed on subsequent scan to be considered a true response.

  within 6 months of treatment

Study Arms (1)

pembrolizumab plus guadecitabine and mocetinostat

EXPERIMENTAL

Pembrolizumab given IV; guadecitabine given SQ, mocetinostat given PO.

Drug: Pembrolizumab; Drug: Guadecitabine; Drug: Mocetinostat

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered at 200mg IV on day 1 of each 21 day cycle.

pembrolizumab plus guadecitabine and mocetinostat

Guadecitabine DRUG

Guadecitabine will be administered subcutaneously given daily on days 1-5 of each cycle with escalating doses by cohort.

pembrolizumab plus guadecitabine and mocetinostat

Mocetinostat DRUG

Mocetinostat will be administered orally with escalating doses on days 8, 10, 13, 15, 17 and 20 of each cycle with escalating doses by cohort.

pembrolizumab plus guadecitabine and mocetinostat

Eligibility Criteria

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

You may qualify if:

• Patient must be capable, willing, and able to provide written, informed consent
• Age ≥ 18 years old
• Histologically-confirmed stage IIIb or IV NSCLC by the enrolling institution
• Patients must have progressed on treatment with an anti-PD1/PD-L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1/PD-L1 treatment progression is defined by meeting all of the following criteria:
• a. Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb b. Has demonstrated disease progression after PD-1/PD-L1 as defined by RECIST v1.1 (if treatment received as part of a clinical trial with formal RECIST reads performed) or a combination of clinical AND radiologic evidence of progression, as determined by the treating investigator. The initial evidence of disease progression (PD) should ideally be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, unless there is rapid clinical progression such that follow up imaging is infeasible.
• i. Note: Second imaging for confirmation of PD can be waived in rapidly progressing patients after consultation with the Sponsor/PI. Progressive disease has been documented within 24 weeks from the last dose of anti-PD-1/PD-L1 mAb.
• Measurable by RECIST v1.1 (those undergoing pre-treatment resection must have imaging assessment after resection to determine measurability)
• a. Previously irradiated sites of tumor may be considered measurable if there is radiographic progression at that site subsequent to the time of completing radiation.
• Have a safely biopsiable tumor lesion and be willing to undergo a pre-treatment and ontreatment core biopsy
• Pretreatment tissue should be collected via core biopsy, ideally of a non-target lesion.
• Patients may not have intervening systemic anti-cancer therapy between the time of pre-treatment biopsy/resection and initiating study treatment.
• ECOG performance status of 0-1.
• Adequate hematologic, renal, and/or hepatic function (following criteria must be met within 28 days of C1D1):
• a. ANC ≥ 1,500/mm3 (≥ 1. 5 × 10\^9/L) b. Hemoglobin ≥ 9.0 g/dL c. Platelet count ≥ 100,000/ul (≥ 100,000 per mm3) d. Serum creatinine ≤ 1.5 x ULN OR, for subjects with creatinine levels \>1.5 x ULN, an estimated creatinine clearance of ≥ 40 mL/min calculated using the Cockcroft and Gault formula ((140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female) e. Total bilirubin ≤ 1.5 x ULN OR, for subjected with total bilirubin levels \>1.5 x ULN, a direct bilirubin ≤ ULN f. AST and ALT ≤ 3 x UNL (unless elevated transaminases are felt to be directly related to metastatic disease involving the liver, in which case AST and ALT must be ≤ 5x ULN)
• Women of childbearing potential (WOCBP) † must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 28 days of C1D1.

You may not qualify if:

• Presence of targetable EGFR mutations or ALK re-arrangements.
• a. All patients with adenocarcinoma histology must be tested for EGFR and ALK status, unless a KRAS mutation is detected in which case EGFR/ALK testing is not required.
• History of allergy to study drug components or history of severe hypersensitivity reaction of any monoclonal antibody.
• History of immune-related adverse event wit prior PD-1/PD-L1 therapy that required discontinuation of treatment
• History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• Any systemic anti-cancer therapy within 3 weeks prior to C1D1 of study therapy, with the following exception:
• a. Any prior investigational anti-cancer therapy is not permitted within 4 weeks of C1D1.
• Ongoing adverse event from previously administered systemic anti-cancer therapy unless has recovered to ≤ grade 1 or at baseline prior to C1D1.
• a. Subjects with any grade alopecia or ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Patients who have not previously been treated with platinum-based based doublet chemotherapy and who, in the judgment of the investigator, have rapidly progressive disease such that serious complications may arise from disease progression within the next 12 weeks will be excluded.
• Non-CNS radiotherapy within 1 week prior to C1D1 of study therapy
• Active infection requiring systemic therapy
• Known history of previous clinical diagnosis of tuberculosis.
• Prior or current systemic immunosuppressive therapy (\> 10 mg/day prednisone equivalents) within 7 days prior to C1D1 of study therapy. Inhaled, ocular, intra-articular, intranasal, and topical corticosteroids are permitted in absence of active autoimmune disease.
• a. Adrenal replacement doses are permitted in the absence of active autoimmune disease.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Astex Pharmaceuticals, Inc.: collaborator
• Mirati Therapeutics Inc.: collaborator
• Stand Up To Cancer: collaborator
• Van Andel Research Institute: collaborator

Study Sites (3)

John Hopkins Medical Center

Baltimore, Maryland, 21287, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

pembrolizumab; guadecitabine; mocetinostat

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Kathryn Arbour, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Single-arm, open-label, multi-center, therapeutic study. All patients will be assigned to receive all three study therapies. The phase 1 portion of the study will proceed as a 3+3 dose-escalation with escalating doses of guadecitabine and mocetinostat, along with fixed dose of pembrolizumab.

Study Record Dates

• First Submitted: July 14, 2017
• First Posted: July 18, 2017
• Study Start: August 4, 2017
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 6, 2025

Record last verified: 2025-08

Locations

US (3)