Key Inclusion Criteria:
Common inclusion criteria for all patients:
1. Are greater than or equal to \[≥\] 18 years of age at the time of informed consent.
2. Have histologically confirmed solid tumor (any type of advanced or metastatic solid tumor for the Hepatic Impairment Arm of the Monotherapy Part), advanced or metastatic NSCLC or CRC and evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1 or iRECIST criteria, as applicable).
3. Willing to provide written informed consent in accordance with federal, local, and institutional guidelines and comply with all requirements of the study.
4. Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective (dual methods of) contraception throughout the study and for 4 months following the last dose of study drug (childbearing potential excludes: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy or hysterectomy); and male patients must use an effective barrier method of contraception throughout the study and for 4 months following the last dose of study drug if sexually active. Male patients must agree not to donate sperm during the study treatment period.
For the Monotherapy Part only (bioavailability/bioequivalence \[BA/BE\] and hepatic impairment \[HI\] arms):
5. Have received at least 1 line of systemic anticancer treatment unless there is no first-line standard of care therapy or standard of care therapy is contraindicated (adjuvant or neoadjuvant therapy is not counted as one line of systemic therapy). Patients must have failed prior standard curative therapy for their disease, must be intolerant to or be ineligible for any potentially curative approved treatment, irrespective of line of therapy.
6. Must have either normal hepatic function, or moderate or severe hepatic impairment (as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria:
1. S20-100 and S100-20 arms: normal hepatic function (total bilirubin and aspartate aminotransferase \[AST\] less than or equal to \[≤\] upper limit of normal \[ULN\]).
Note: Patients with mild hepatic dysfunction (total bilirubin greater than \[\>\] 1 to 1.5 × ULN or AST \> ULN) may be included if liver function tests are stable for the past 3 months and enrollment is approved in writing by the Sponsor's Medical Monitor.
2. MHI arm: ≥1 week of documented moderate hepatic impairment (total bilirubin \>1.5-3 × ULN, any level of AST).
3. SHI arm: ≥1 week of documented severe hepatic impairment (total bilirubin \>3-10 × ULN, any level of AST).
For Combination Therapy Part only:
7. Previous treatment lines (adjuvant or neoadjuvant therapy is not counted as one line of systemic therapy):
1. Arm A: For patients with NSCLC, have received 1-2 prior lines of systemic anti-cancer treatment with 1 regimen including an anti-PD-1/L1 monoclonal antibody (mAb)
2. Arm B: For patients with RAS mutant CRC, 1-2 prior lines of systemic treatments, and no prior anti- programmed cell death protein 1/L1 monoclonal antibody (anti-PD-1/L1 mAb).
* KRAS WT: have 1-3 prior lines of systemic treatments.
* KRAS mutant (at least 50 percent \[%\] of patients): 1-2 prior lines of systemic treatments.
3. Arm C: For patients with CRC participating in the combination arm with FOLFIRI, 1-2 prior lines of systemic therapy are allowed.
4. Arm B and C in CRC: patient with CRC who are not candidates for curative resection of metastatic lesions.
8. Must have hepatic function as follows:
1. Arm A (combination with docetaxel): Patients with NSCLC who are to receive docetaxel and have bilirubin ≤ ULN, and AST and/or alanine transaminase (ALT) ≤ 1.5 x ULN.
2. Arm B and C: total bilirubin ≤ 1.5 × ULN and AST ≤ 2.5 x ULN, AST ≤ 2.5 x ULN; for Arm B, unless bilirubin elevation is related to Gilbert's Syndrome for which bilirubin must be ≤ 4 x ULN.
Key Exclusion Criteria:
Common exclusion criteria for all patients:
1. Have inadequate hematopoietic function defined as (without transfusion or growth factor support within 7 days prior to first dose):
1. For S20-100 or S100-20 arms: absolute neutrophil count (ANC) \<1.5 × 10\^9/liter (L); platelet count (PLT) \<100 × 10\^9/L; or hemoglobin (Hb) \<10 gram per deciliter (g/dL).
2. For Arms A-C: ANC \<1.5 × 10\^9/L; PLT \<100 × 10\^9/L; or Hb \<10 g/dL.
2. Have inadequate renal function defined as a calculated creatinine clearance (CrCl) of: a. all patients: \<20 mL/min using the formula of Cockcroft and Gault.
3. Have any other medical condition especially any gastrointestinal (GI) dysfunctions or GI disease that could interfere with the absorption of selinexor (e.g., inability to swallow or retain oral medications, malabsorption syndrome, a history of GI surgery which may result in intestinal blind loop, significant gastroparesis, unresolved nausea, vomiting, or diarrhea \[National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade \>1\]).
4. Ongoing infection requiring parenteral antibiotics, antivirals, or antifungals on Day 1 dosing.
a. All patients: on Day 1 dosing.
5. Prior exposure to a SINE compound or selinexor.
6. Insufficient time since or not recovered from procedures or anti-cancer therapy, defined as:
1. Not recovered from major surgery ≤21 days for Arms A, B, and C prior to Day 1 dosing. Minor procedures, such as biopsies, dental work, or placement of a port or intravenous (IV) line for infusion are permitted.
2. Have ongoing clinically significant anti-cancer therapy-related toxicities CTCAE Grade \>1. Patients with any of the following will not be excluded: immune checkpoint-related endocrinopathies that are well controlled with hormonal supplements, patients with electrolyte abnormalities that are well-managed with supplementation, patients with Grade 2 lymphopenia, or patients with alopecia of any grade. In specific cases, patients whose toxicity has stabilized or with Grade 2 non-hematologic toxicities can be allowed following documented approval by the Sponsor's Medical Monitor.
3. Had last dose of previous anti-cancer therapy ≤14 days prior to Day 1 dosing.
4. Palliative radiotherapy \>14 days prior to the study is allowed.
5. Received investigational drugs in other clinical trials within 28 days, or 5 half-lives of the investigational drug (whichever is shorter), prior to Cycle 1 Day 1 (C1D1).
7. Serious active psychiatric or active medical condition that could interfere with participation in the study or in the opinion of the Investigator would make study involvement unreasonably hazardous for Arms A-C.
8. Known allergy to selinexor (all patients), docetaxel (NSCLC Arm A only), pembrolizumab (CRC arm B only), 5-FU, leucovorin, or irinotecan (CRC Arm C only).
9. Female patients who are pregnant or breastfeeding.
For Monotherapy Part only (BA/BE and HI arms):
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of:
1. ≥3 for patients to be enrolled into the S20-100 or S100-20 arms of the study.
2. ≥4 for patients to be enrolled into the MHI and SHI arms of the study.
11. For MHI and SHI arms: ANC \<1 × 10\^9/L; PLT \<75 × 10\^9/L; or Hb \<8 g/dL.
12. Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to Day 1 dosing OR strong CYP3A inducers ≤14 days prior to Day 1 dosing.
13. Inability or unwillingness to undergo a series of PK sampling.
For Combination Therapy Part only:
14. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≥3 for Arms A and B and ECOG PS ≥2 for Arm C.
15. Arm B patients with CRC who are to receive pembrolizumab:
1. Had a diagnosis of immunodeficiency or are receiving systemic steroid therapy (\>10 milligram per day \[mg/day\] of prednisone or equivalent) or any other form of immunosuppressive therapy.
2. Patients with controlled diabetes mellitus and patients with endocrinopathies on stable hormone replacement therapy, are eligible for the trial.
3. Have active autoimmune disease requiring systemic treatment during the past 2 years. Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted.
Note: The Investigator needs to evaluate the patient's medical history to confirm that they are eligible to receive the combination with pembrolizumab per these criteria.
4. For patients with CRC who have received live-attenuated vaccine against an infectious disease (e.g., nasal spray influenza vaccine) ≤14 days prior to the intended C1D1 of the Combination Therapy.
16. Arm C: Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. Note: for patients who are initially enrolled onto the BA/BE arm in the monotherapy part and plan to switch to combination therapy after completing the planned dosing and PK sample collection, dose interruption between the Monotherapy Part and the Combination Therapy Part is allowed for recovery from AEs. Patients requiring \>21 days to recover from toxicities related to selinexor should be discussed with the Sponsor's Medical Monitor for documented approval to continue to the Combination Therapy Part if inclusion/exclusion criteria are met. Experiencing PD during the Monotherapy Part does not constitute exclusion from the Combination Therapy Part.
