Advanced Solid TumorPhase 1NCT06724042
Study of ISM5939 in Patients With Advanced and/or Metastatic Solid Tumors
A Phase 1 study testing ISM5939, Cisplatin and Docetaxel in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by InSilico Medicine Hong Kong Limited.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Metastatic Solid Tumor, Advanced and/or Metastatic Solid Tumors
- What is being tested?
- ISM5939, Cisplatin and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 159 participants
- Where
- No sites listed yet
- Study dates
- 30 Dec 2026to 30 Dec 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged ≥18 years.
- 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.
- 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.
- Patients enrolled in Part 3 (combination cohorts) must be acceptable and eligible for treatment with cisplatin, docetaxel, or pembrolizumab.
- Measurable disease per RECIST version 1.1 or PCWG3 criteria for patients with metastatic castration-resistant prostate cancer.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
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- 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.
- Patients must have an understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Patient must be capable of oral administration of ISM5939 and not have any clinically significant gastrointestinal abnormalities that may alter absorption.
- Adequate bone marrow and organ function.
- If receiving corticosteroids, patient must be maintained on a stable or decreasing dose for at least 7 days prior to Day 1.
- Life expectancy ≥3 months in the opinion of the investigator.
Who cannot join
- 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.
- 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.
- Treatment with any investigational agent administered within 30 days or 5 half-lives, whichever is shorter, before the first dose of ISM5939.
- Prior therapy with an ENPP1 inhibitor.
- 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.
- Major surgery within 21 days prior to Day 1.
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- 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.
- Patients with a primary CNS tumor.
- Patient has uncontrolled hypertension, or heart disease and/or cardiac repolarization abnormality, or uncontrolled systemic infection.
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: First-in-human Phase 1a/b, Open-Label, Multicenter, Dose Escalation, Optimization and Expansion Study of ISM5939 in Patients With Advanced and/or Metastatic Solid Tumors
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.
- Being tested
- ISM5939, Cisplatin, Docetaxel, Pembrolizumab
- Keywords
- ISM5939, Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ENPP1 inhibitor, Solid Tumor
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISM5939Drug
ISM5939 tablets will be administered orally once daily (QD).
CisplatinDrug
Cisplatin will be administered intravenously in combination with ISM5939 on day 1 during each cycle.
DocetaxelDrug
Docetaxel will be administered intravenously in combination with ISM5939 on day 1 during each cycle.
PembrolizumabDrug
Pembrolizumab will be administered intravenously in combination with ISM5939 on day 1 during each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Dose escalation | Experimental | An open-label dose escalation of ISM5939 administered orally as a single agent in patients with advanced or metastatic solid tumors. Receives: Drug: ISM5939 |
| Part 2 Dose optimization | Experimental | 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. Receives: Drug: ISM5939 |
| Part 3 Dose expansion | Experimental | 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. Receives: Drug: ISM5939; Drug: Cisplatin; Drug: Docetaxel; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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]).
Measured: Approximately 36 months
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.
Measured: Approximately 36 months
Secondary outcomes (7)
Maximum concentration (Cmax)
Blood samples for Pharmacokinetics (PK) analysis will be assessed after dose of ISM5939.
Measured: Approximately 36 months
Area under the concentration-time curve (AUC)
Blood samples for Pharmacokinetics (PK) analysis will be assessed after dose of ISM5939.
Measured: Approximately 36 months
Terminal half-life (t1/2)
Blood samples for Pharmacokinetics (PK) analysis will be assessed after dose of ISM5939.
Measured: Approximately 36 months
Objective response rate (ORR)
ORR is defined as the percentage of participants with Complete Response or Partial Response.
Measured: Approximately 36 months
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.
Measured: Approximately 36 months
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).
Measured: Approximately 36 months
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.
Measured: Approximately 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start30 Dec 2026 (estimated)
- Primary completion30 Dec 2029 (estimated)
- Study completion30 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 159 participants (estimated)
Sponsor and investigators
- Lead sponsor
- InSilico Medicine Hong Kong Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06724042
- Sponsor's protocol ID
- ISM5939-101
- Status last verified
- Dec 2025
- First submitted
- 1 Dec 2024
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-in-human Phase 1a/b, Open-Label, Multicenter, Dose Escalation, Optimization and Expansion Study of ISM5939 in Patients With Advanced and/or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT06724042
- Acronym / sponsor ID
- ISM5939-101
- Keywords
- ISM5939, Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ENPP1 inhibitor, Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 159 participants (estimated)
- Lead sponsor
- InSilico Medicine Hong Kong LimitedIndustry (pharma, biotech, devices)
- Study start
- 30 Dec 2026 (estimated)
- Primary completion
- 30 Dec 2029 (estimated)
- Study completion
- 30 Dec 2030 (estimated)
- First posted
- 9 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1 Dose escalation | Experimental | Drug: ISM5939An open-label dose escalation of ISM5939 administered orally as a single agent in patients with advanced or metastatic solid tumors. |
| Part 2 Dose optimization | Experimental | Drug: ISM5939ISM5939 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. |
| Part 3 Dose expansion | Experimental | Drug: ISM5939, Drug: Cisplatin, Drug: Docetaxel, Drug: PembrolizumabThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients aged ≥18 years.
- 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.
- 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.
- Patients enrolled in Part 3 (combination cohorts) must be acceptable and eligible for treatment with cisplatin, docetaxel, or pembrolizumab.
- Measurable disease per RECIST version 1.1 or PCWG3 criteria for patients with metastatic castration-resistant prostate cancer.
Key exclusion criteria (11 listed)
- 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.
- 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.
- Treatment with any investigational agent administered within 30 days or 5 half-lives, whichever is shorter, before the first dose of ISM5939.
- Prior therapy with an ENPP1 inhibitor.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISM5939ISM5939 tablets will be administered orally once daily (QD). | Drug | Part 1 Dose escalation, Part 2 Dose optimization, Part 3 Dose expansion |
| CisplatinCisplatin will be administered intravenously in combination with ISM5939 on day 1 during each cycle. | Drug | Part 3 Dose expansion |
| DocetaxelDocetaxel will be administered intravenously in combination with ISM5939 on day 1 during each cycle. | Drug | Part 3 Dose expansion |
| PembrolizumabPembrolizumab will be administered intravenously in combination with ISM5939 on day 1 during each cycle. | Drug | Part 3 Dose expansion |
Primary outcome
Dose-limiting toxicities (DLTs) occurrence
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
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.
Adverse events (AEs)
Time frame: Approximately 36 months
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]).
Recommended Phase 2 doses (RP2Ds)
Time frame: Approximately 36 months
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.
7 secondary outcomes
Maximum concentration (Cmax)
Time frame: Approximately 36 months
Area under the concentration-time curve (AUC)
Time frame: Approximately 36 months
Terminal half-life (t1/2)
Time frame: Approximately 36 months
Objective response rate (ORR)
Time frame: Approximately 36 months
Duration of response (DOR)
Time frame: Approximately 36 months
Disease control rate (DCR)
Time frame: Approximately 36 months
Best overall response (BOR)
Time frame: Approximately 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ISM5939, Cisplatin and Docetaxel in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by InSilico Medicine Hong Kong Limited.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Insilico Study team (+86 021-50831718, Insilico-Clinicaltrial@insilico.ai), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicities (DLTs) occurrence (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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.