A Study to Investigate APL-5125 in Adults With Advanced Solid Tumors

Inclusion Criteria:

* 18 years or older
* Phase 1: Histologically confirmed locally advanced, inoperable, or metastatic tumor; Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma.
* For Phase 1 sub-studies: Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma, Pancreatic Adenocarcinoma, Gastric Adenocarcinoma, Endometrial Adenocarcinoma, Triple Negative Breast Cancer, Ovarian Cancer, Prostate Cancer
* Phase 2: Colorectal carcinoma
* No available standard of care therapy or participant is ineligible for standard of care therapy, except in CRC tumor type in which participant must have previously received all the following therapeutic agents:

  * fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy
  * an anti-VEGF therapy
  * if wt-RAS (wt-KRAS and wt-NRAS), an anti-EGFR therapy
* Eastern Cooperative Oncology Group (ECOG) ≤1
* Body Weight ≥40 kg.
* Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must be willing to use specific contraception or avoid intercourse
* Male participants must be willing to use specific contraception and not plan to impregnate a female partner or donate sperm while on study
* Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial

Exclusion Criteria:

* Certain medical conditions such as: active brain metastases, carcinomatous meningitis, unstable angina pectoris, myocardial infarction or clinically significant ventricular arrhythmias, symptomatic congestive heart failure, uncontrolled active infection, history of significant hemorrhage within 4 weeks of the first dose date, intestinal disease or major gastric surgery, arterial thrombosis within 6 months of screening
* Certain prior therapies such as: anti-cancer treatment within 2 weeks of Cycle 1 Day 1, prior radiotherapy within 14 days before screening, active anti-coagulation therapy, over the counter or prescription medications within 14 days or 5 half-lives prior to cycle 1 day 1, herbal medicines and supplements within 14 days
* Major surgery within 1 month of screening
* Hemoglobin \< 9.0 g/dL
* Absolute neutrophil count \< 1.5 x 10\^9/L
* Platelet count \< 100 x 10\^9/L
* Hepatic function:

  1. Aspartate aminotransferase and/or alanine aminotransferase (ALT) \>3 × upper limit of normal (ULN) (\>5 x ULN for subjects with liver metastases)
  2. Total bilirubin \>1.5 × ULN (except participants with Gilbert's syndrome).
  3. Albumin \< 3 g/dL
* Calculated or measured creatinine clearance of \<60 mL/minute calculated using the formula of Cockcroft and Gault (\[140 - Age\] × Mass \[kg\] / \[72 × serum creatinine mg/dL\]). Multiply result by 0.85 if female.
* Fridericia's corrected QT interval (QTcF) \>470 msec or a family history of Long QT Syndrome.
* Cardiac function: Echocardiogram (or MUGA) showing Left Ventricular Ejection Fraction (LVEF) \<45% at rest
* Infectious diseases: positive for HIV (unless controlled with active retroviral therapy), hepatitis B and hepatitis C