Clinical Trial 23367

• Overview

  Study Title:

  First-in-Human, Escalating Oral Dose Study of RGT-419B Given Alone and with Endocrine Therapy in Subjects with Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced/Metastatic Breast Cancer

  Objective:

  Primary Objective * Assess the safety and tolerability of daily doses of RGT-419B administered to subjects with HR+, HER2- ABC to identify the MTD of RGT-419B when given as singlet or doublet therapy as determined by the number of subjects who have a DLT confirmed in the first 28-day cycle of RGT-419B treatment. Doublet therapy will include the combination of RGT-419B with the Investigator s choice of a locally approved AI, SERD or SERM. MTD for QD / BID dosing may be different. * Assess the safety and tolerability of repeated cycles of RGT-419B with (doublet) or without (singlet) the Investigator s choice of a locally approved AI, SERD or SERM. * Assess the plasma and urine PK profile of RGT-419B and its two major metabolites, RGT-570A and RGT-880, following single and multiple doses of RGT-419B (as singlet and/or doublet therapy (with an AI, SERD or SERM) administered to subjects with HR+, HER2- ABC. If RGT-570A and RGT-880 metabolites occur at low levels in human subjects, i.e., <10% of total auc it will not be necessary to monitor subjects for formation of these metabolites in all cohorts if rgt-419b occurs at low levels in urine relative to the dosage e.g.><10% of the total dose amount it may not be necessary to collect urine pk samples from patients in all cohorts. exploratory food effect efe will be implemented in the monotherapy dose expansion phase assess the time to number of and rates of clinical responses including objective response rate orr progression free survival pfs overall survival os and clinical benefit rate cbr in subjects as defined by recist v.1.1. explore further the recommended phase ii dose rp2d of rgt-419b by expanding 150 mg qd and 150 mg bid cohorts with approximate 20 subjects for each cohort.>

• Treatments

  Therapies:

  CDK4/6 Inhibitor

  Medications:

  RGT419B ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Provide a signed and dated informed consent document executed personally or by a legal health-care proxy.
  • Be a male or female ≥18 years of age with HR+, HER2- ABC.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. (Table 10, ECOG Performance Status. (Azam et al., 2019)
  • Be able and willing to provide a report demonstrating immunohistochemistry testing of hormone receptors (ER with or without PR) and HER2 from the subject’s most recent biopsy specimen performed by a locally certified laboratory [e.g., College of American Pathologists (CAP)-certified laboratory in US] following signed consent but prior to the initiation of any screening procedures.
  • Subjects must be assessed by the Investigator to have measurable disease according to RECIST v.1.1. Measurable disease is defined as: At least one lesion, not previously irradiated, that can be measured accurately at baseline (by CT or MRI or physical examination). Lesion must be ≥10 mm on longest diameter (except lymph nodes which must have a short axis ≥15 mm).
  • Be willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
  • Be willing to use one of the protocol-specified types of highly effective birth control. With the exception of female subjects of non-childbearing potential all female subjects must commit to use effective contraception through 28 days after last dose of IP and all male subjects must commit to use effective contraception through 90 days after last dose of IP
  • Have adequate baseline laboratory studies (hematologic and chemistry) and organ function including renal, liver, and bone marrow function.
  • Be able to swallow orally administered medications (e.g., capsules, tablets, liquids).
  • Have no known contraindication to receiving RGT-419B such as a known sensitivity to any constituent of the investigational product (IP). (n.b., RGT-419B is primarily metabolized through cytochrome P450 in rats and dogs in vivo and human cells in vitro. It was not a strong CYP inhibitor or inducer in these assays. (See Section 5.2.2)
  • have had all acute or residual toxic effects of any prior therapy resolved to baseline severity (or CTCAE Grade 1) except for AEs such as grade 1 taxane-induced neuropathy, any grade alopecia, amenorrhea, or other toxicities not considered a safety risk for the subject in the Investigator's opinion.
  • Must have Eastern Cooperative Oncology (ECOG) performance status of 0 or 1.
  • Must have a life expectancy of ≥12 weeks.
  • Other criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Subjects must not have visceral metastases with severe organ dysfunction as evidenced by signs and symptoms, laboratory studies, lymphangitic spread and/or rapid progression of disease.
  • Subjects who meet the protocol’s definition of WOCBP with a positive urine pregnancy test within 72 hours of C1D1 will be excluded prior to administration of any study drugs. Female subjects with urine tests not confirmed to be negative will be required to have a serum pregnancy test.
  • Subjects must not be planning to conceive children within the projected duration of the study, starting with the screening visit through 30 days (± 7 days) after the last dose of study drug.
  • Subjects must not have had prior irradiation to >25% of the bone marrow and/or inadequate bone marrow function or evidence of clinically significant end-organ damage.
  • Subjects must meet the washout periods prior to C1D1 for prior therapies and procedures, and must have recovered from all related toxicities as detailed in the protocol.
  • Subjects must not have another serious medical condition that is not well controlled with locally approved medications allowed by the protocol.
  • Subjects must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to the drugs used in the study.
  • Subjects must not have clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality as described by the protocol.
  • Subjects who cannot comply with concomitant medication restrictions will not be enrolled.
  • Other criteria may apply.

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