Clinical Trials /

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

NCT03220477

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer.
  • Official Title: Phase I/Ib Study of Combined Pembrolizumab Plus Guadecitabine and Mocetinostat for Patients With Advanced NSCLC (DOSE SELECTION)

Clinical Trial IDs

  • ORG STUDY ID: 17-241
  • NCT ID: NCT03220477

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
Pembrolizumabpembrolizumab plus guadecitabine and mocetinostat
Guadecitabinepembrolizumab plus guadecitabine and mocetinostat
Mocetinostatpembrolizumab plus guadecitabine and mocetinostat

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
pembrolizumab plus guadecitabine and mocetinostatExperimentalPembrolizumab given IV; guadecitabine given SQ, mocetinostat given PO.
  • Pembrolizumab
  • Guadecitabine
  • Mocetinostat

Eligibility Criteria

        Inclusion Criteria:

          -  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

               1. Pretreatment tissue should be collected via core biopsy, ideally of a non-target
                  lesion.

               2. 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.

             † A woman of childbearing potential is a sexually mature female who: has not undergone
             a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for
             at least 24 consecutive months (i.e. has had menses at any time in the preceding 24
             consecutive months).

          -  Effective contraception:

               1. Women of childbearing potential must agree to practice 2 effective methods of
                  contraception from the time of signing the informed consent form through 120 days
                  after the last dose of study therapy, or agree to completely abstain from
                  heterosexual intercourse.

               2. Male subjects, even if surgically sterilized (i.e., status post vasectomy) must
                  agree to 1 of the following: practice effective barrier contraception during the
                  entire study treatment period and through 120 days after the last dose of study
                  therapy, or agree to completely abstain from heterosexual intercourse.

          -  Willing to comply with clinical trial instructions and requirements, including
             mandatory biopsies.

        Exclusion Criteria:

          -  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.

          -  Has diagnosis of immunodeficiency

          -  History of allogeneic organ transplant.

          -  Patients with known or suspected history of autoimmune disease.

             a. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone
             replacement, resolved childhood asthma/atopy, patients with asthma requiring
             intermittent bronchodilator therapy, skin disorders (such as vitiligo, psoriasis, or
             alopecia) not requiring systemic treatment, or conditions not expected to recur in the
             absence of an external trigger are permitted to enroll.

             i. 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.

          -  Other active malignancy that is progressing, requires concurrent intervention, and/or
             could be mistaken for the malignancy under study during disease assessments.

          -  Patients with previous malignancies (except non-melanoma skin cancers, and the
             following in situ cancers: bladder, gastric, colon, cervical/dysplasia, melanoma, or
             breast) are excluded unless definitive therapy has been completed at least 1 year
             prior to study entry and the patient is now without evidence of disease from that
             malignancy and no additional therapy is required or anticipated to be required during
             the study period.

          -  Known untreated brain or leptomeningeal metastasis.

             a. Patients with brain metastases are eligible if metastases have been adequately
             treated and neurologically returned to baseline (except for residual signs or symptoms
             related to the CNS treatment) for at least two weeks prior to C1D1 and meet
             requirements related to steroids noted in above Exclusions Criteria 6.2.10.

          -  History of stroke or transient ischemic attack within the previous 6 months.

          -  Any of the following cardiac abnormalities:

               1. Unstable angina pectoris

               2. Congestive heart failure ≥ NYHA Class 3

               3. QTc ≥470 milliseconds calculated using Frediricia's Correction

               4. Current or history of pericardial effusion causing hemodynamic compromise

          -  Patients with a >/= small pericardial effusion at baseline will be excluded. Patients
             with < small pericardial effusion at baseline can continue to proceed onto treatment
             if other eligibility criteria are met

          -  History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis
             which required steroid treatment, or any evidence of clinically active interstitial
             lung disease.

          -  Any positive test for HIV 1/2 antibodies and/or RNA.

          -  Any positive test for hepatitis B virus(HBV) using HBV surface antigen (HBV sAG) test
             or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
             antibody test indicating acute or chronic infection.

          -  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.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or 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 received a live vaccine within 30 days of planned start of study therapy. a.
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:number of patients with adverse events
Time Frame:1 year
Safety Issue:
Description: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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Pembrolizumab
  • guadecitabine
  • mocetinostat
  • 17-241

Last Updated

August 6, 2021