This is a first-in-human Phase 1a/b, open-label, multicenter, dose escalation, optimization and expansion study of ISM5939 to evaluate the safety, tolerability, PK, PD, and preliminary antitumor activity of ISM5939 in patients with advanced or metastatic solid tumors.

The study will be conducted in 3 parts sequentially: Part 1 dose escalation ISM5939 monotherapy, Part 2 dose optimization to determine RP2D of ISM5939 monotherapy, and Part 3 dose expansion in 3 cohorts after initial safety run-in of ISM5939 combination therapy.

Inclusion Criteria:

1. Patients aged ≥18 years.
2. Patients with histologically or cytologically confirmed diagnosis of advanced/metastatic solid tumor that is either locally advanced and not amenable to curative therapy or stage 4 disease.
3. Patients must have tumor relapse/recurrence and be refractory to available SOC treatment, be intolerant to or ineligible for available SOC treatment, or have no SOC treatment available.
4. Patients enrolled in Part 3 (combination cohorts) must be acceptable and eligible for treatment with cisplatin, docetaxel, or pembrolizumab.
5. Measurable disease per RECIST version 1.1 or PCWG3 criteria for patients with metastatic castration-resistant prostate cancer.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
7. Patients must have recovered to Grade 1 or baseline levels from toxicity or AEs related to prior treatment for their cancer, excluding: Grade ≤2 neuropathy; alopecia of any grade, or skin pigmentation; Grade ≤2 hypothyroidism stable on hormone replacement therapy, Grade ≤2 anorexia or fatigue.
8. Patients must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
9. Patient must be capable of oral administration of ISM5939 and not have any clinically significant gastrointestinal abnormalities that may alter absorption.
10. Adequate bone marrow and organ function.
11. If receiving corticosteroids, patient must be maintained on a stable or decreasing dose for at least 7 days prior to Day 1.
12. Life expectancy ≥3 months in the opinion of the investigator.

Exclusion Criteria:

1. Patient has had prior systemic anti-cancer therapy within 3 weeks or at least 5 half-lives (whichever is shorter, but no less than 2 weeks) prior to Day 1.
2. Prior radiation therapy at the target lesion, unless there is evidence of disease progression and the prior radiation therapy is to have been completed at least 7 days before study drug.
3. Treatment with any investigational agent administered within 30 days or 5 half-lives, whichever is shorter, before the first dose of ISM5939.
4. Prior therapy with an ENPP1 inhibitor.
5. Currently receiving any of the CYP3A4/5 inhibitors/inducers, or CYP2C9 inhibitors, or inhibitors/inducers of MDR1, or medications known to prolong the QT interval that cannot be discontinued 14 days or 5 half-lives prior to Day 1.
6. Major surgery within 21 days prior to Day 1.
7. Patients with active (uncontrolled, metastatic) second malignancies or requiring therapy, or who have undergone potentially curative therapy with no evidence of the disease recurrence for at least 3 years prior to the first dose of study treatment.
8. Patients with a primary CNS tumor.
9. Patient has uncontrolled hypertension, or heart disease and/or cardiac repolarization abnormality, or uncontrolled systemic infection.
10. Other medical illness that, in the opinion of the investigator, may impact the safety of the patient or the objectives of the study.

Other protocol inclusion and exclusion criteria may apply.