1. Subjects must be ≥18 years old at signing of informed consent. Type of Subject and Disease Characteristics:

2. Locally advanced and unresectable or metastatic (ie, advanced) disease and/or lesions that are not amenable to definitive radiotherapy.

3. Measurable disease by RECIST v1.1. a. Subjects with disease limited to the bone are eligible if there is at least 1 measurable soft-tissue component according to RECIST v1.1.

4. Must provide archival FFPE tumor tissue before enrollment. Sample is to be from the most recent biopsy, if available. If archival tumor tissue is not available, a fresh tumor tissue biopsy is required (except for subjects with bone-only disease). a. For dose escalation only: subjects who do not have adequate archival tissue and for whom biopsy is contraindicated may be enrolled after approval by the medical monitor.

5. Minimum life expectancy of >12 weeks according to the investigator’s judgement.

6. ECOG PS score of 0 or 1.

7. Adequate organ function as defined below. a. Hematological: − ANC ≥1 500/µL. − Platelets ≥100 000/µL. − Hemoglobin ≥9 g/dL without transfusion for at least 2 weeks before enrollment or without erythropoiesis-stimulating agents (eg, Epo, Procrit®) for at least 6 weeks before enrollment. b. Renal: Creatinine clearance ≥50 mL/min calculated using the Cockcroft--Gault formula [(140 – age)×(weight in kg)×(0.85 if female) / 72×(serum creatinine in mg/dL)] or as measured using 24-hour urine collection. c. Hepatic:  − Serum total bilirubin ≤1.5 × institutional ULN or ≤2.0×ULN if the subject has a diagnosis of Gilbert syndrome or ≤3.0×ULN for subjects with liver metastases − AST/SGOT and/or ALT/SGPT ≤3.0×ULN or AST and/or ALT ≤3.0×ULN with documented liver metastases. d. Coagulation: − INR or PT ≤1.5×ULN unless the subject is receiving anticoagulant therapy and as long as PT or aPTT is within the therapeutic range of intended use of anticoagulants. − aPTT ≤1.5×ULN unless the subject is receiving anticoagulant therapy and as long as PT or aPTT is within the therapeutic range of intended use of anticoagulants. 

8. Willing and able to comply with study visits and study procedures.

9. Able to swallow tablets intact without chewing or crushing.

Informed Consent:
10. Subjects must be capable of giving signed informed consent as described in Appendix 1, Section 10.1.3.2, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 

Subjects are excluded from the study if any of the following criteria apply: Subjects with HER2-Positive aBC:

1. Have had more than 1 prior line of therapy with an antibody-drug conjugate. Subjects with HR-Positive, HER2-Negative aBC:

2. Have potentially immediately life-threatening visceral organ involvement. Subjects with KRAS mutant aCRC:

3. Have BRAFV600E mutation, HER2amp, or dMMR/MSI-H tumors. Subjects with KRAS Mutant aNSCLC:

​​​​​​​4. Have tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1/BRAF/RET/MET/EGFR exon20 insertion/NTRK/HER2).