This is a Phase I, first-in-human (FIH), open-label, non-randomized, multi-center study to explore the safety, tolerability, pharmacokinetics and preliminary antitumor activity of NMS-03597812 in adult patients with RRMM who have exhausted standard treatment options that are expected to provide meaningful clinical benefit or for whom standard therapy is considered unsuitable.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
All patients will receive NMS-03597812 administered orally once daily on Days 1-21 in repeated 4-week cycles.
All patients will receive NMS-03597812 administered orally once daily on Days 1-21 and Dexamethasone administered orally once a week on Days 1, 8, 15 and 22 in repeated 4-week cycles.
Dana- Farber Cancer Institute
Boston, Massachusetts, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Number of Participants with first-cycle dose limiting toxicity
For DLT evaluation, severity (grade) is classified according to common terminology criteria for adverse events version 5.0 (CTCAE v5.0).
Time frame: Time interval between the date of the first dose administration in Cycle 1 (each cycle is 28 days) and the date of the first dose administration in Cycle 2 which is expected to be 28 days or up to 42 days in case of dose delay due to toxicity
Number of participants with Adverse Events (AEs)
Safety will be assessed by adverse events (AEs), which include clinically significant abnormalities identified during a medical test (e.g. laboratory tests, electrocardiogram, vital signs, physical examinations). AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) and their severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). The analysis will focus on the events reported after the start of treatment (treatment emergent adverse events).
Time frame: From the Informed Consent signature to 28 days after the last dose of study treatment administration
Number of Participants by Best Tumor response
Number of patients with best tumor response achieved on treatment is determined using International Myeloma Working Group (IMWG) Criteria 2016. The number of patients is provided for each category: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD), Progressive Disease (PD) and Not Evaluable (NE).
Time frame: From treatment start date until disease progression or relapse (up to approximately 12 months).
Number of Participants with Overall Response
Best Overall Response is measured for patients achieving Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) as Best Response according to International Myeloma Working Group (IMWG) Criteria 2016
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Time frame: From treatment start date until disease progression or relapse (up to approximately 12 months).
Number of Participants with Clinical Benefit
Clinical Benefit is measured for patients achieving Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR) or Minimal Response (MR) as Best Response according to International Myeloma Working Group (IMWG) Criteria 2016.
Time frame: From treatment start date until disease progression or relapse (up to approximately 12 months).
Duration of Response
Duration of Response is calculated in patients achieving overall response by International Myeloma Working Group (IMWG) Criteria 2016, as the time elapsed from the date at which Overall response is first observed to the date of first observed disease progression/relapse or date of death due to progression, whichever comes first
Time frame: From the first responding tumor assessment until Progression Disease/Relapse or Death due to Progression (up to approximately 12 months)
Progression Free Survival (PFS)
Progression Free Survival (PFS) is calculated as the time elapsed from the date of treatment initiation to the date of first documentation of disease progression/relapse according to International Myeloma Working Group (IMWG) Criteria 2016, or death due to any cause, whichever comes first
Time frame: From date of first dose of study drug up to the date of first documentation of disease progression/relapse or death due to any cause, whichever comes first (up to approximately 12 months).
Maximum concentration (Cmax) of NMS-03597812 after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21 at different timepoints.
Time to maximum plasma concentration (Tmax) of NMS-03597812 after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21, at different timepoints.
Area under the plasma concentration versus time curve up to the last detectable plasma concentration (AUClast) of NMS-03597812 after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21, at different timepoints.
Minimum plasma concentration (Cmin) of NMS-03597812 after single and multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21, at different timepoints.
Average plasma concentration (Cave) of NMS-03597812 after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21, at different timepoints.
Area under the plasma concentration versus time curve to infinity (AUCinf) of NMS-03597812 after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and Cycle 2 on Days 1, 8, 15, 21 at different timepoints.
Terminal elimination half-life (t1/2) of NMS-03597812 after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and Cycle 2 on Days 1, 8, 15, 21, at different timepoints
Oral plasma clearance (CL/F) of NMS-03597812 after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21, at different timepoints.
Apparent volume of distribution (Vd/F) of NMS-03597812 after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21, at different timepoints
Accumulation ratio (Rac) of NMS-03597812 after multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Time frame: At Cycle 1 (each cycle is 28 days) on Days 1, 2, 8, 15, 21, 22, 23 and 24 and at Cycle 2 on Days 1, 8, 15, 21, at different timepoints
Renal clearance of NMS-03597812 after multiple doses of drug.
Urine samples will be used for PK assessments. Samples will be collected in patients treated in the dose escalation phase, starting from cohort 4 or from the occurrence of the first DLT, whichever comes first, and in all patients treated in the dose expansion.
Time frame: At Cycle 1 (each cycle is 28 days) Day 1 and Day 21
Cumulative amount recovered unchanged in the urine (Ae) of NMS-03597812 after multiple doses of drug
Urine samples will be used for PK assessments. Samples will be collected in patients treated in the dose escalation phase, starting from cohort 4 or from the occurrence of the first DLT, whichever comes first, and in all patients treated in the dose expansion.
Time frame: At Cycle 1 (each cycle is 28 days) Day 1 and Day 21
Cumulative amount recovered unchanged in the urine expressed as a fraction of administered dose (Ae%) of NMS-03597812 after multiple doses of drug.
Urine samples will be used for PK assessments. Samples will be collected in patients treated in the dose escalation phase, starting from cohort 4 or from the occurrence of the first DLT, whichever comes first, and in all patients treated in the dose expansion.
Time frame: At Cycle 1 (each cycle is 28 days) Day 1 and Day 21