INCLUSION CRITERIA

          1. Written informed consent obtained prior to any screening procedures and in accordance
             with federal, local, and institutional guidelines.

          2. Age ≥ 18 years.

             INDICATION-SPECIFIC INCLUSION CRITERIA

             Relapsed/Refractory Multiple Myeloma (Parts A1, A2, and B):

          3. Symptomatic, histologically confirmed multiple myeloma (MM) and evidence of disease
             progression, based on International Myeloma Working Group (IMWG) guidelines.

          4. Participants receiving hematopoietic growth factor support including erythropoietin,
             darbepoetin, granulocyte-colony stimulating factor, granulocyte macrophage-colony
             stimulating factor, and platelet stimulators can continue to do so, but must be
             transfusion independent for at least 1 week prior to Cycle 1 Day 1 (C1D1) in the
             study.

             Relapsed/Refractory Colorectal Cancer (Part C):

          5. Histological or cytological documentation of adenocarcinoma of the colon or rectum.

          6. Documented evidence of progressive disease according to Response Evaluation Criteria
             in Solid Tumors (RECIST) Version 1.1.

             Relapsed/Refractory Metastatic Castration-resistant Prostate Cancer (Parts D and E):

          7. Histologically confirmed adenocarcinoma of the prostate with archival tumor tissue
             available for molecular analyses. If the participants does not have a prior
             histological diagnosis, then a fresh biopsy at screening may be used for this purpose.

          8. Participants should not be transfusion dependent.

          9. Part E only: Participants currently receiving treatment with abiraterone and
             appropriate to continue in the opinion of the Investigator. Participants must also
             have been on and continue on a stable dose of corticosteroids (prednisone or
             dexamethasone) for 30 days prior to C1D1.

             Higher Risk Myelodysplastic Syndrome (Part F):

         10. Documented diagnosis of MDS with 5-19% myeloblasts.

         11. Participants should be intermediate-2 or high-risk MDS by International Prognostic
             Scoring System (IPSS).

         12. Participants believed to be IPSS high risk, without clearly meeting IPSS categories
             above should be discussed with the medical monitor prior to enrolling.

         13. Hypomethylating agents (HMA) refractory participants including:

               1. ≥ 2 cycles of azacitidine and/or decitabine or experimental agents (such as
                  SGI-110 or ASTX727 or similar) with clear progressive disease (PD) (no count
                  recovery with ≥50% increase in bone marrow blasts) OR

               2. ≥ 4 cycles of azacitidine and/or decitabine (or other hypomethylating therapy)
                  with lack of improvement (no CR/CRi/PR/HI).

         14. Participants receiving a stable dose of erythropoiesis-stimulating agent (ESA) for at
             least 1 month at the time of study entry may continue to receive ESA.

         15. Participants in Part F Phase 2 with RR high-risk myelodysplastic Syndrome should have
             documented diagnosis of MDS with 5 to 19 percentage myeloblasts in the bone marrow.

         16. Participants in Part G with Newly Diagnosed Intermediate/ High-risk Myelodysplastic
             Syndrome should have diagnosis of MDS with 5 to 19 percentage myeloblasts in the bone
             marrow.

        EXCLUSION CRITERIA

        Participants in All Parts of the Study:

          1. Major surgery within 4 weeks before C1D1.

          2. Impaired cardiac function or clinically significant cardiac diseases.

          3. Uncontrolled active severe systemic infection requiring parenteral antibiotics,
             antivirals, or antifungals within one week prior to C1D1.

          4. Participants with known symptomatic brain metastasis.

          5. Prior malignancies:

               1. Participants in All Parts of the Study: Participants with adequately resected
                  basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in
                  situ (i.e. cervix) may enroll irrespective of the time of diagnosis.

               2. Participants with Higher Risk MDS only: Concomitant malignancies or previous
                  malignancies with less than a 1-year disease free interval at the time of
                  enrollment.

          6. Participants with gastrointestinal tract disease (or uncontrolled vomiting or
             diarrhea) that could interfere with the absorption of eltanexor (or ASTX727 in Part
             G).

             INDICATION-SPECIFIC EXCLUSION CRITERIA

             Relapsed/Refractory Multiple Myeloma (RRMM) (Parts A1, A2 and B):

          7. Time since the last prior therapy for treatment of RRMM:

               1. Radiation, chemotherapy, immunotherapy or any other anticancer therapy, including
                  investigational anticancer therapy <=2 weeks prior to C1D1.

               2. Palliative steroids for disease related symptoms are allowed up to 3 days prior
                  to C1D1.

               3. Participants must have recovered or stabilized (<=Grade 1 or to their baseline)
                  from toxicities related to their previous treatment except for alopecia.

          8. Participants with active graft versus host disease after allogeneic stem cell
             transplantation. At least 3 months must have elapsed since completion of allogeneic
             stem cell transplantation.

          9. Grade >2 peripheral neuropathy or Grade 2 peripheral neuropathy with pain within 2
             weeks prior to C1D1.

             Relapsed/Refractory Colorectal Cancer (Part C):

         10. Radiotherapy, chemotherapy, or any other anticancer therapy, including investigational
             anticancer therapy within 2 weeks prior to Screening. Participants must have recovered
             from clinically significant toxicities. The site of irradiation should have evidence
             of progressive disease (new lesions or increase in lesion size) if this is the only
             site of disease.

         11. Participants who have been treated with their most recent chemotherapy or
             investigational drugs <=21 days or 5 half-lives (whichever is longer) prior to the
             first dose of study treatment, and/or have any acute toxicities due to prior
             chemotherapy and/ or radiotherapy that have not resolved to a National Cancer
             Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
             Grade 0 or Grade 1 with the exception of chemotherapy induced alopecia and Grade 2
             peripheral neuropathy.

             Relapsed/Refractory Metastatic Castration-Resistant Prostate Cancer (Parts D and E):

         12. Participants who have been treated with their most recent chemotherapy or
             investigational drugs <=21 days or 5 half-lives (whichever is longer) prior to the
             first dose of study treatment, and/or have any acute toxicities due to prior
             chemotherapy and/ or radiotherapy that have not resolved to a NCI CTCAE v4.03 Grade 0
             or Grade 1 with the exception of chemotherapy induced alopecia and Grade 2 peripheral
             neuropathy.

         13. Initiating bisphosphonate therapy or adjusting bisphosphonate dose/regimen within 30
             days prior to C1D1. Participants on a stable bisphosphonate or denosumab regimen are
             eligible and may continue.

             Higher risk Myelodysplastic Syndrome (Part F Phase 2 and Part G):

         14. IPSS very low or low-1 risk MDS.

         15. Evidence of transformation to AML by World Health Organization (WHO) (≥20% blasts in
             bone marrow or peripheral blood).

         16. Participants receiving granulocyte-colony stimulating factor (G-CSF) or granulocyte
             macrophage-colony stimulating factor (GM-CSF) within the 3 weeks prior to C1D1.