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, Appendicealadenocarcinoma, Pancreatic Adenocarcinoma, Gastric Adenocarcinoma, EndometrialAdenocarcinoma, Triple Negative Breast Cancer, Ovarian Cancer, Prostate Cancer

• Phase 2: Colorectal carcinoma

• No available standard of care therapy or participant is ineligible for standard ofcare therapy, except in CRC tumor type in which participant must have previouslyreceived 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 pregnancytest at screening; must not plan to become pregnant or have ova harvested orbreastfeed while on study; must be willing to use specific contraception or avoidintercourse

• Male participants must be willing to use specific contraception and not plan toimpregnate a female partner or donate sperm while on study

• Participant must be willing and able to provide written informed consent and tocomply with the requirements of the trial

Exclusion Criteria:

• Certain medical conditions such as: active brain metastases, carcinomatousmeningitis, unstable angina pectoris, myocardial infarction or clinicallysignificant ventricular arrhythmias, symptomatic congestive heart failure,uncontrolled active infection, history of significant hemorrhage within 4 weeks ofthe first dose date, intestinal disease or major gastric surgery, arterialthrombosis 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-coagulationtherapy, over the counter or prescription medications within 14 days or 5 half-livesprior 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 × upperlimit 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 theformula of Cockcroft and Gault ([140 - Age] × Mass [kg] / [72 × serum creatininemg/dL]). Multiply result by 0.85 if female.

• Fridericia's corrected QT interval (QTcF) >470 msec or a family history of Long QTSyndrome.

• Cardiac function: Echocardiogram (or MUGA) showing Left Ventricular EjectionFraction (LVEF) <45% at rest

• Infectious diseases: positive for HIV (unless controlled with active retroviraltherapy), hepatitis B and hepatitis C