A Dose Exploration Study With Birabresib (MK-8628) in Participants With Selected Advanced Solid Tumors (MK-8628-006)
Condition: NUT Midline Carcinoma (NMC); Triple Negative Breast Cancer (TNBC); Non-small Cell Lung Cancer (NSCLC); Castration-resistant Prostate Cancer (CRPC)
MeSH terms: Triple Negative Breast Neoplasms
Intervention: Birabresib
Intervention description: Administered as an oral capsule in a fasted state
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: OTX015; MK-8628

Summary:

      This is a study to determine the recommended dose of birabresib (MK-8628)(formerly known as
      OTX015) for further studies in participants with advanced nuclear protein in testis (NUT)
      midline carcinoma (NMC), triple negative breast cancer (TNBC), non-small cell lung cancer
      (NSCLC), or castration-resistant prostate cancer (CRPC). This is a two-part parallel study:
      Part A will establish the recommended dose by evaluating dose limiting toxicity (DLT),
      safety, discontinuation, and early efficacy and Part B will enroll participants with NMC only
      and will evaluate safety and efficacy in this population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females ≥18 years of age for NSCLC, TNBC, and CRPC

          -  Males and females ≥16 years of age for NMC

          -  Diagnosis of one of the following advanced solid tumors for which standard therapy
             either does not exist or has proven ineffective, intolerable or inacceptable for the
             participant: NMC;TNBC; NSCLC; or CRPC

          -  Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1. CRPC participants may be enrolled with objective evidence of disease as
             per Prostate Cancer Working Group (PCWG2) criteria

          -  Life expectancy ≥3 months

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1

          -  Have an interval of ≥3 weeks (or ≥2 weeks for NMC participants) since chemotherapy (≥6
             weeks for nitrosoureas or mitomycin C), immunotherapy, hormone therapy or any other
             anticancer therapy or surgical intervention resection, or ≥3 half-lives for monoclonal
             antibodies, or ≥5 half-lives for other non-cytotoxic agents (whichever is longer)

          -  CRPC participants must maintain ongoing androgen deprivation therapy with a
             gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing
             serum testosterone is <50 ng/dL (<1.7 nmol/L)

          -  Participants receiving bisphosphonate or denosumab therapy must be on stable doses for
             at least 4 weeks before start of study therapy

          -  Females must not be pregnant (negative urine or serum human chorionic gonadotropin
             test within 72 hours of study start)

          -  Females of childbearing potential and male participants must agree to use adequate
             contraception starting with the first dose of trial treatment through 90 days after
             the last dose of study medication

        Exclusion Criteria:

          -  Has inability to swallow oral medications or presence of a gastrointestinal disorder
             (e.g. malabsorption) deemed to jeopardize intestinal absorption of birabresib

          -  Has persistent grade >1 clinically significant toxicities related to prior
             antineoplastic therapies (except for alopecia). Stable sensory neuropathy ≤ grade 2
             National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events
             (CTCAE) Version 4.0 is accepted

          -  Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS
             metastases. Treated and stable CNS metastases are allowed.

          -  History of prior or concomitant malignancies within 3 years of study start

          -  Have other serious illness or medical condition, such as active infection, unresolved
             bowel obstruction, psychiatric disorders, or cerebrovascular accident within 1 year of
             study start

          -  Known human immunodeficiency virus (HIV) and/or active Hepatitis B or C infections

          -  Have one of the following cardiac-related conditions: Congestive heart failure or
             angina pectoris (except if medically controlled); myocardial infarction (within 1 year
             of study start); uncontrolled hypertension; or uncontrolled arrhythmias

          -  Other concomitant anticancer treatment

          -  Participation in another clinical trial or treatment with any investigational drug
             (excluding anticancer treatments) within 30 days of study start

          -  Concomitant therapy with strong CYP3A4 inhibitors or inducers

          -  Therapeutic anticoagulation (e.g. warfarin, heparin, etc.) must be stopped at least 7
             days prior to the first dose of birabresib. Low-dose low molecular weight heparin
             (LMWH) is permitted

          -  Is pregnant or breast-feeding