ClinicalTrials.gg
Not yet recruitingNCT06724042Updated Jul 23, 2026

Study of ISM5939 in Patients With Advanced and/or Metastatic Solid Tumors

A Phase 1 interventional study of ISM5939 and Cisplatin in Advanced Solid Tumor, Metastatic Solid Tumor and Advanced and/or Metastatic Solid Tumors, sponsored by InSilico Medicine Hong Kong Limited. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-23.

Sponsored by InSilico Medicine Hong Kong Limited · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
159
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Advanced Solid Tumor
  • Metastatic Solid Tumor
  • Advanced and/or Metastatic Solid Tumors

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Keywords

  • ISM5939
  • Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)
  • ENPP1 inhibitor
  • Solid Tumor
03

In context

Neoplasm Metastasis

4,040 studies on the registry are indexed under Neoplasm Metastasis; 886 are open to participants now.

This study's planned enrollment of 159 is above the median of 50 across 3,268 interventional studies indexed under Neoplasm Metastasis.

Browse Neoplasm Metastasis studies →

Lead sponsor

InSilico Medicine Hong Kong Limited is the lead sponsor of 11 studies on the registry; 8 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Patients aged ≥18 years.
  2. Patients with or cytologically confirmed diagnosis of advanced/ 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 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. per version 1.1 or PCWG3 criteria for patients with metastatic castration-resistant prostate cancer.
  6. (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 gastrointestinal abnormalities that may alter absorption.
  10. Adequate bone marrow and organ function.
  11. If receiving , patient must be maintained on a stable or decreasing dose for at least 7 days prior to Day 1.
  12. ≥3 months in the opinion of the investigator.

Exclusion criteria

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 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 /5 inhibitors/inducers, or CYP2C9 inhibitors, or inhibitors/inducers of MDR1, or medications known to prolong the 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, ) second 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.

Terms in these criteria, in plain language(13)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
159 participants (estimated)

Study arms

  • Experimental
    Part 1 Dose escalation

    An open-label dose escalation of ISM5939 administered orally as a single agent in patients with advanced or metastatic solid tumors.

    Drug: ISM5939

  • Experimental
    Part 2 Dose optimization

    ISM5939 will be administered orally as a single agent in patients with advanced or metastatic solid tumors in 2 selected dose levels to determine RP2D of ISM5939 monotherapy.

    Drug: ISM5939

  • Experimental
    Part 3 Dose expansion

    This will be an open-label evaluation of ISM5939 administered orally in combination with cisplatin, docetaxel, or pembrolizumab in patients with selected advanced solid tumors. Each of the combination cohort will start with safety run-in dose escalation for ISM5939. Subsequent subjects will then be enrolled in combination expansion cohorts with a fixed dose of ISM5939 selected by safety review committee.

    Drug: ISM5939 · Drug: Cisplatin · Drug: Docetaxel · Drug: Pembrolizumab

Interventions

  • DrugISM5939

    ISM5939 tablets will be administered orally once daily (QD).

  • Cisplatin will be administered intravenously in combination with ISM5939 on day 1 during each cycle.

  • Docetaxel will be administered intravenously in combination with ISM5939 on day 1 during each cycle.

  • Pembrolizumab will be administered intravenously in combination with ISM5939 on day 1 during each cycle.

06

What researchers measure

Primary outcomes

  1. Dose-limiting toxicities (DLTs) occurrence

    DLT is defined as any of the adverse event which meets DLT criteria if assessed at least possibly related to study treatment and not clearly related to progressive disease or other extraneous cause and occurring during the DLT period.

    Time frame: Day 1 up to Day 28 for Part 1 and Day 1 up to Day 21 for Part 3 safety run-in dose escalation period

  2. Adverse events (AEs)

    Incidence and severity of AEs will be evaluated based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 \[NCI CTCAE v5.0\]).

    Time frame: Approximately 36 months

  3. Recommended Phase 2 doses (RP2Ds)

    The maximum tolerated dose (MTD) or RP2Ds in patients with advanced or metastatic solid tumors will be determined based on the available data of safety and tolerability, PK, PD and preliminary activity from all dosed patients.

    Time frame: Approximately 36 months

Secondary outcomes

  1. Maximum concentration (Cmax)

    Blood samples for Pharmacokinetics (PK) analysis will be assessed after dose of ISM5939.

    Time frame: Approximately 36 months

  2. Area under the concentration-time curve (AUC)

    Blood samples for Pharmacokinetics (PK) analysis will be assessed after dose of ISM5939.

    Time frame: Approximately 36 months

  3. Terminal half-life (t1/2)

    Blood samples for Pharmacokinetics (PK) analysis will be assessed after dose of ISM5939.

    Time frame: Approximately 36 months

  4. Objective response rate (ORR)

    ORR is defined as the percentage of participants with Complete Response or Partial Response.

    Time frame: Approximately 36 months

  5. Duration of response (DOR)

    DOR is defined as the time from the first tumor assessment when the Complete Response/Partial Response is met to the date of disease progression or death, which occurs first.

    Time frame: Approximately 36 months

  6. Disease control rate (DCR)

    DCR is defined as the percentage of participants with Complete Response or Partial Response or Stable Disease (persisted for at least 6 weeks).

    Time frame: Approximately 36 months

  7. Best overall response (BOR)

    BOR is defined as the best response from the initial oral dose of ISM5939 until disease progression, initiation of another anti-tumor treatment, or early withdrawal (whichever occurs first). Confirmation of CR and PR is required.

    Time frame: Approximately 36 months

07

Study locations

No study locations are listed for this record.

08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 23, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT06724042
Lead sponsor
InSilico Medicine Hong Kong Limited
Responsible party
Sponsor
First posted
Dec 9, 2024
Start date
Dec 30, 2026 (estimated)
Primary completion
Dec 30, 2029 (estimated)
Completion
Dec 30, 2030 (estimated)
Last update
Jul 23, 2026

Study contacts

Insilico Study team
Contact
Insilico-Clinicaltrial@insilico.ai
+86 021-50831718

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.

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