ON 123300 (Narazaciclib) and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Able to provide a signed Written Informed Consent: Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care * Male or female patients ≥18 years * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Symptomatic MM having progressed on ≥2 prior line of therapies - including 1 proteasome inhibitor (bortezomib, carfilzomib etc.), 1 immunomodulatory drug (lenalidomide, pomalidomide, thalidomide etc.), and 1 CD38 targeting monoclonal antibody (daratumumab, isatuximab) either as monotherapy or in combination. Refractoriness (progression while on therapy or ≤60 days after discontinuation of therapy) to prior line of therapy is not required. * Subjects who received BCMA-targeted immune-effector therapies like CAR-T cells and/or bispecific antibodies prior can be enrolled provided they are ≥60 days out of the treatment. * Subjects must not be candidates for treatment regimens known to provide clinical benefit to be eligible for this study. * Subjects must have measurable disease defined by at least 1 of the following 4 measurements: * Serum M-protein \> 0.5 g/dL or Urine M-protein \> 200 mg/24 hours * Light chain MM without measurable disease in serum or urine: Serum immunoglobulin free light chain assay: involved free light chain level \>10 mg/dL (\> 100 mg/L) provided the serum free light chain ratio is abnormal * For oligo/non-secretory myeloma, measurable by standard imaging (PET/CT or MRI) ± bone marrow biopsy if myeloma biomarkers are inconclusive or non-contributory * Able to swallow and absorb oral medication * All previous therapies for cancer, including radiotherapy, major surgery and investigational therapies discontinued for ≥ 14 days before study entry, and all acute effects of any prior therapy resolved to baseline severity or Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE v5.0) excluding alopecia or fatigue. * Adequate organ or marrow function * CrCl (Cockcroft-Gault equation) ≥ 45ml/min * ALT/AST ≤2 times upper limit of normal * Total bilirubin ≤2 times upper limit of normal (\<3 x ULN for congenital hyperbilirubinemia states like Gilbert Syndrome) * Corrected serum calcium ≤12.5mg/dL or free ionized calcium ≤6.5mg/dL * ANC ≥1 x 109/L (prior growth factor permitted but must be without support 7 days before screening test) * Hemoglobin ≥8g/dL (without blood transfusion in 7 days prior to test, recombinant erythropoietin permitted) * Platelets ≥50 x 109/L * No active infections (including but not limited to HIV, Hepatitis B, Hepatitis C, tuberculosis) or chronic health conditions which may interfere in the study in the opinion of the investigator. * HIV: undetectable HIV viral load and CD4 counts \>200 for \>6 months on continuous antiretroviral therapy may be screened. * Hepatitis B: If HbcAb positive and HBV PCR-, may be screened * Hepatitis C: if completed anti-viral therapy and in sustained virological response \>6 months, may be screened * Tuberculosis: Quantiferon or skin prick test positive but with negative chest imaging * (CXR or CT) and asymptomatic, may be screened * Note: A line of therapy consists of ≥1 complete cycle of a single agent, a regimen consisting of a * combination of several drugs, or a planned sequential therapy of various regimens3. * A treatment is considered a new line of therapy if any one of the following three conditions are met: * Start of a new line of treatment after discontinuation of a previous line: if the treatment regimen is discontinued for any reason, and a different regimen is started, it should be considered a new line of therapy. A regimen is considered to have been discontinued if all the drugs in that given regimen have been stopped. The regimen is not considered to have been discontinued if some of the drugs of the regiment, but not all, have been discontinued. * The unplanned addition or substitution of one or more drugs in an existing regimen: Unplanned addition of a new drug, or switching to a different drug, or combination of drugs due to any reason, is considered a new line of therapy. * Stem cell transplant (SCT): In patients undergoing \>1 SCT, except in the case of a planned tandem SCT with a predefined interval such as 3 months, each SCT (autologous or allogeneic, should be considered a new line of therapy, regardless of whether the conditioning regime used is the same or different. Exclusion Criteria: * Active plasma cell leukemia at screening (\>5% plasma cells by standard differential), Waldenstroms macroglobulinemia, PEOMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes), known active or prior CNS involvement or exhibits meningeal signs (extradural skull or spinal mass causing extrinsic mass effect is not excluded) or clinically significant amyloidosis. * History of allogeneic hematopoietic cell transplantation (HCT), or other cellular therapy product, within 60 days. * Inability to tolerate oral medication, presence of poorly controlled gastrointestinal disease, or dysfunction that could affect study drug absorption including but not limited to: * Diarrhea \> Grade 1, based on the NCI CTCAE grading, in the absence of antidiarrheals. * Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing. * Following cardiac conditions: * New York Heart Association (NYHA) stage III or IV congestive heart failure * myocardial infarction or coronary artery bypass graft (CABG) \<6 months prior to enrollment * History of clinically significant ventricular arrhythmia or unexplained syncope not believed to be vasovagal in nature or due to dehydration * History of severe nonischemic cardiomyopathy e. Impaired cardiac function (LVEF \<45%) as assessed by echocardiogram or multi gated acquisition (MUGA) scan. * Stroke or seizure within 6 months of enrollment * Are at risk for Torsades de pointes (TdP): Patients who have a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval \>470 msec) using Fredericia's QT correction formula, or who have a history of additional risk factors for TdP (eg, heart failure, hypokalemia, family history of Long QT Syndrome), or who are currently taking medications that prolong the QT/QTc interval. * Are currently taking or within 5 half-lives of taking strong inducers and inhibitors of cytochrome P450 enzyme (CYP) 2C8 and CYP3A4. * Have had major surgery within 14 days prior to screening to allow for postoperative healing of the surgical wound and site(s). * Have received recent (within 28 days prior to screening) live attenuated vaccines. * Active pregnancy or breastfeeding females * Known chronic alcohol or drug abuse * Lack of capacity to sign consent and/or participate in the trial * Any other condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents. * Any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent or limit compliance with study requirements. * Prior or concurrent malignancy, except for the following: * Adequately treated non-melanoma skin cancer (basal cell or squamous cell skin carcinoma) ≥1 year * Cervical carcinoma in situ adequately treated ≥1 year * Adequately treated Stage I or II cancer from which the subject is currently in complete remission ≥2 years * Any other cancer from which the subject has been disease-free for ≥ 3 years * Males or females of childbearing potential who do not agree to practice 2 highly effective methods of contraception. Highly effective method of contraception has a failure rate of less than 1% per year when used consistently and correctly, and agree to remain on a highly effective method of contraception from the time of signing the informed consent form through 90 days after the last dose of study drug. For women, examples of highly effective contraceptives include A) user independent methods: 1. implantable progesterone only hormonal contraception 2. intrauterine device/intrauterine hormone releasing system 3. vasectomized partner B) user dependent methods: 1. combined estrogen and protestor hormonal contraception (oral intravaginal or transdermal) 2. progesterone only hormone contraception (oral or injectable). For men, highly effective barrier method of contraception include - condom with spermicidal foam/gel/film/cream/suppository from the time of signing the ICF until 90 days after receiving the last dose of treatment. Intercourse with a pregnant woman must involve the use a condom. Women and men must agree not to donate eggs or sperm while on the study drug or up to 90 days after the last dose of drug. * Uncontrolled, untreated or active infections, including but not limited to HIV, Hepatitis B, Hepatitis C, tuberculosis.