Solid Tumor, AdultPhase 1/2NCT04665206
Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors
A Phase 1/2 study testing VT3989, Nivolumab & Ipilimumab and Osimertinib in people with Solid Tumor, Adult and Mesothelioma, run by Vivace Therapeutics, Inc at 12 sites in 2 countries.
Trial summary
This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered, alone or in combination, once daily in patients with mesothelioma and/or metastatic solid tumors that are resistant to standard therapy or for which no effective standard… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult, Mesothelioma, NSCLC
- What is being tested?
- VT3989, Nivolumab & Ipilimumab and Osimertinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 434 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 24 Mar 2021to 2 Mar 2030
- Phase
- Phase 1/2
- 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
- Part 3 Combination Cohort A: Patients with pathologically diagnosed, metastatic or unresectable malignant mesothelioma (including both pleural and non-pleural) who have not received systemic therapy.
- Part 3 Combination Cohort B: Patients with pathologically diagnosed incurable locally advanced (inoperable or recurrent), or metastatic NSCLC with exon 19 deletions or exon 21 L858R mutations, with or without prior treatment with Osimertinib.
- Part 3 Combination Cohort C: Patients with pathologically diagnosed metastatic or unresectable malignant pleural mesothelioma who have not received systemic chemotherapy.
- Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors or modified RECIST v1.1 for malignant pleural mesothelioma. mRECIST may be used for pleural extension of non-pleural mesothelioma or for mixed pleural and peritoneal (or other) mesothelioma.
- ECOG: 0-1.
- Adequate organ functions, including the liver, kidneys, and hematopoietic system.
Who cannot join
- Active brain metastases or primary CNS (central nervous system) tumors.
- History of leptomeningeal metastases
- Active or chronic, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- Known HIV positive or active Hepatitis B or Hepatitis C
- Clinically significant cardiovascular disease and prior exposure to cardiotoxic agents.
- Corrected QT (QTcF) interval > 470 msec (using Fridericia's correction formula).
Show all 9Show fewer
- Additional active malignancy that may confound the assessment of the study endpoints
- Women who are pregnant or breastfeeding
- Prior treatment with TEAD inhibitor.
Trial locations and contacts
12 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 2 countries
United States9 sites, 9 recruiting
- Recruiting
Virginia Cancer Specialists, PC
Arlington, Virginia, 22201
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
University of Chicago Medical Center
Chicago, Illinois, 60637
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
M Health Fairview University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Heather Fritz, 650-627-7437, hfritz@inclin.com
Australia3 sites, 3 recruiting
- Recruiting
Monash Health
Clayton, Victoria, 3168
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
Peter MacCullum Cancer Centre
Melbourne, Victoria, 3000
Heather Fritz, 650-627-7437, hfritz@inclin.com
- Recruiting
Linear Clinical Research
Nedlands, Western Australia, 6009
Heather Fritz, 650-627-7437, hfritz@inclin.com
About this study
Official title: Phase I/II, Multi-Center, Open-Label Study of VT3989, Alone or in Combination, in Patients With Locally Advanced or Metastatic Solid Tumors
This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered, alone or in combination, once daily in patients with mesothelioma and/or metastatic solid tumors that are resistant to standard therapy or for which no effective standard therapy is available.
Read the detailed description
Dose escalation (Part 1) will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with metastatic solid tumors or mesothelioma. The 3 + 3 design will be implemented until the MTD or recommended phase 2 dose(s) and schedule(s) are determined. The MTD is defined as the highest dose level at which < 33% of patients experience a dose limiting toxicity (DLT) during the first cycle of the study (Cycle 1).
Dose Expansion (Part 2) will further evaluate the safety and assess preliminary antitumor activity at the recommended phase 2 dose(s) and schedule(s) with up to 6 cohorts. Expansion cohorts 1 and 2 will enroll patients with mesothelioma of any site origin with or without NF2 mutations. Expansion cohort 3 will enroll non-pleural mesothelioma patients. Expansion cohort 4 will enroll solid tumor patients with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements. Cohort 5 will enroll pleural mesothelioma patients.
Combination part (Part 3) includes three cohorts. Cohort A will enroll mesothelioma patients who will receive VT3989 in combination with immunotherapy (nivolumab plus ipilimumab). Cohort B will enroll NSCLC patients whose tumors have exon 19 deletion or exon 21 L858R mutation and will receive VT3989 in combination with targeted therapy (Osimertinib). Cohort C will enroll mesothelioma patients who will receive VT3989 in combination with chemotherapy (pemetrexed plus carboplatin).
- Conditions
- Solid Tumor, Adult, Mesothelioma, NSCLC
- Being tested
- VT3989, Nivolumab & Ipilimumab, Osimertinib, Pemetrexed/Carboplatin
- Medical subject headings
- Mesothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VT3989Drug
25, 50, 100, 150 or 200 mg capsules for oral administration.
Nivolumab & IpilimumabDrug
Nivolumab infusion - 360 mg every 3 weeks, 30-minute intravenous infusion
Ipilimumab infusion - 1 mg/kg every 6 weeks, 30-minute intravenous infusion
OsimertinibDrug
40 or 80 mg tablets for oral administration
Pemetrexed/CarboplatinDrug
Pemetrexed infusion: 500 mg/m2 intravenous infusion Carboplatin infusion: AUC 5.0 intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| VT3989 Dose Escalation [Not Recruiting] | Experimental | VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase Receives: Drug: VT3989 |
| Dose Expansion [Not Recruiting] | Experimental | VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma. Receives: Drug: VT3989 |
| Combination [Recruiting] | Experimental | For Cohort A and B, VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib). For Cohort C, VT3989 dosed in 21 day cycles in patients with mesothelioma in combination with chemotherapy (pemetrexed+carboplatin) for 4-6 cycles, then continuing VT3989 as monotherapy on 28-day cycle. Receives: Drug: VT3989; Drug: Nivolumab & Ipilimumab; Drug: Osimertinib; Drug: Pemetrexed/Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Dose Limiting Toxicity
Incidence of Adverse and Serious Adverse Events
Measured: over the first 21 days of dosing
Occurrence of General Toxicity
Incidence of Adverse and Serious Adverse Events, Discontinuations due to Adverse Events and general safety evaluations
Measured: through study completion, an average of 30 months
Secondary outcomes (7)
Tumor Response
Determined by RECIST v1.1 or modified RECIST v1.1
Measured: through study completion, an average of 30 months
Pharmacokinetic Evaluation - Cmax
Peak plasma concentration of VT3989
Measured: for first 6 cycles
Pharmacokinetic Evaluation - Tmax
Time to reach peak plasma concentration of VT3989
Measured: for first 6 cycles
Pharmacokinetic Evaluation - Half-life
Time required for the plasma concentration of VT3989 to reduce by half after reaching peak
Measured: for first 6 cycles
Overall survival
The overall survival of the enrolled patients from starting VT3989 treatment
Measured: At 6, 12, 18 and 24 months
Progression free survival
The progression free survival of the enrolled patients from starting VT3989 treatment
Measured: At 6, 12, 18 and 24 months
Quality of life assessment (Part 2, expansion cohort 3, 4, and 5)
Assessing the Quality of life changes via patient reported outcomes
Measured: Through study completion, an average of 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2020
- Study start24 Mar 2021
- Primary completion2 Nov 2029 (estimated)
- Study completion2 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumor, AdultStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Part 1 dose escalation: 3 + 3 design Part 2 dose expansion: up to 6 cohorts Part 3 combination: 3 cohorts
- Masking
- None (open label)
- Enrolment
- 434 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vivace Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Neelesh Sharma, MD, Study director, Vivace Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04665206
- Sponsor's protocol ID
- VT3989-001
- Status last verified
- Mar 2026
- First submitted
- 5 Dec 2020
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yap TA, Kwiatkowski DJ, Dagogo-Jack I, Offin M, Zauderer MG, Kratzke R, Desai J, Body A, Millward M, Tolcher AW, Raghav KPS, Thurston A, Post L, Dorr FA, Tang TT, Li Y, Sharma N, Kindler HL. YAP/TEAD inhibitor VT3989 in solid tumors: a phase 1/2 trial. Nat Med. 2025 Dec;31(12):4281-4290. doi: 10.1038/s41591-025-04029-3. Epub 2025 Oct 19.
PubMed 41111090
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II, Multi-Center, Open-Label Study of VT3989, Alone or in Combination, in Patients With Locally Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04665206
- Acronym / sponsor ID
- VT3989-001
- Conditions
- Solid Tumor, Adult, Mesothelioma, NSCLC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 434 participants (estimated)
- Lead sponsor
- Vivace Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- 24 Mar 2021 (actual)
- Primary completion
- 2 Nov 2029 (estimated)
- Study completion
- 2 Mar 2030 (estimated)
- First posted
- 11 Dec 2020 (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 an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered, alone or in combination, once daily in patients with mesothelioma and/or metastatic solid tumors that are resistant to standard therapy or for which no effective standard therapy is available.
Detailed description
Dose escalation (Part 1) will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with metastatic solid tumors or mesothelioma. The 3 + 3 design will be implemented until the MTD or recommended phase 2 dose(s) and schedule(s) are determined. The MTD is defined as the highest dose level at which < 33% of patients experience a dose limiting toxicity (DLT) during the first cycle of the study (Cycle 1).
Dose Expansion (Part 2) will further evaluate the safety and assess preliminary antitumor activity at the recommended phase 2 dose(s) and schedule(s) with up to 6 cohorts. Expansion cohorts 1 and 2 will enroll patients with mesothelioma of any site origin with or without NF2 mutations. Expansion cohort 3 will enroll non-pleural mesothelioma patients. Expansion cohort 4 will enroll solid tumor patients with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements. Cohort 5 will enroll pleural mesothelioma patients.
Combination part (Part 3) includes three cohorts. Cohort A will enroll mesothelioma patients who will receive VT3989 in combination with immunotherapy (nivolumab plus ipilimumab). Cohort B will enroll NSCLC patients whose tumors have exon 19 deletion or exon 21 L858R mutation and will receive VT3989 in combination with targeted therapy (Osimertinib). Cohort C will enroll mesothelioma patients who will receive VT3989 in combination with chemotherapy (pemetrexed plus carboplatin).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Part 1 dose escalation: 3 + 3 design Part 2 dose expansion: up to 6 cohorts Part 3 combination: 3 cohorts
| Arm | Type | Receives |
|---|---|---|
| VT3989 Dose Escalation [Not Recruiting] | Experimental | Drug: VT3989VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase |
| Dose Expansion [Not Recruiting] | Experimental | Drug: VT3989VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma. |
| Combination [Recruiting] | Experimental | Drug: VT3989, Drug: Nivolumab & Ipilimumab, Drug: Osimertinib, Drug: Pemetrexed/CarboplatinFor Cohort A and B, VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib). For Cohort C, VT3989 dosed in 21 day cycles in patients with mesothelioma in combination with chemotherapy (pemetrexed+carboplatin) for 4-6 cycles, then continuing VT3989 as monotherapy on 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Part 3 Combination Cohort A: Patients with pathologically diagnosed, metastatic or unresectable malignant mesothelioma (including both pleural and non-pleural) who have not received systemic therapy.
- Part 3 Combination Cohort B: Patients with pathologically diagnosed incurable locally advanced (inoperable or recurrent), or metastatic NSCLC with exon 19 deletions or exon 21 L858R mutations, with or without prior treatment with Osimertinib.
- Part 3 Combination Cohort C: Patients with pathologically diagnosed metastatic or unresectable malignant pleural mesothelioma who have not received systemic chemotherapy.
- Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors or modified RECIST v1.1 for malignant pleural mesothelioma. mRECIST may be used for pleural extension of non-pleural mesothelioma or for mixed pleural and peritoneal (or other) mesothelioma.
- ECOG: 0-1.
Key exclusion criteria (9 listed)
- Active brain metastases or primary CNS (central nervous system) tumors.
- History of leptomeningeal metastases
- Active or chronic, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- Known HIV positive or active Hepatitis B or Hepatitis C
- Clinically significant cardiovascular disease and prior exposure to cardiotoxic agents.
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 |
|---|---|---|
| VT398925, 50, 100, 150 or 200 mg capsules for oral administration. | Drug | Combination [Recruiting], Dose Expansion [Not Recruiting], VT3989 Dose Escalation [Not Recruiting] |
| Nivolumab & IpilimumabNivolumab infusion - 360 mg every 3 weeks, 30-minute intravenous infusion Ipilimumab infusion - 1 mg/kg every 6 weeks, 30-minute intravenous infusion | Drug | Combination [Recruiting] |
| Osimertinib40 or 80 mg tablets for oral administration | Drug | Combination [Recruiting] |
| Pemetrexed/CarboplatinPemetrexed infusion: 500 mg/m2 intravenous infusion Carboplatin infusion: AUC 5.0 intravenous infusion | Drug | Combination [Recruiting] |
Primary outcome
Occurrence of Dose Limiting Toxicity
Time frame: over the first 21 days of dosing
Incidence of Adverse and Serious Adverse Events
Occurrence of General Toxicity
Time frame: through study completion, an average of 30 months
Incidence of Adverse and Serious Adverse Events, Discontinuations due to Adverse Events and general safety evaluations
7 secondary outcomes
Tumor Response
Time frame: through study completion, an average of 30 months
Pharmacokinetic Evaluation - Cmax
Time frame: for first 6 cycles
Pharmacokinetic Evaluation - Tmax
Time frame: for first 6 cycles
Pharmacokinetic Evaluation - Half-life
Time frame: for first 6 cycles
Overall survival
Time frame: At 6, 12, 18 and 24 months
Progression free survival
Time frame: At 6, 12, 18 and 24 months
Quality of life assessment (Part 2, expansion cohort 3, 4, and 5)
Time frame: Through study completion, an average of 30 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 2 Apr 2026.
- Derived from this study: PubMed 41111090Yap TA, Kwiatkowski DJ, Dagogo-Jack I, Offin M, Zauderer MG, Kratzke R, Desai J, Body A, Millward M, Tolcher AW, Raghav KPS, Thurston A, Post L, Dorr FA, Tang TT, Li Y, Sharma N, Kindler HL. YAP/TEAD inhibitor VT3989 in solid tumors: a phase 1/2 trial. Nat Med. 2025 Dec;31(12):4281-4290. doi: 10.1038/s41591-025-04029-3. Epub 2025 Oct 19.
- Individual participant dataSharing planned: No
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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.
Neelesh Sharma, MD study director
Vivace Therapeutics
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing VT3989, Nivolumab & Ipilimumab and Osimertinib in people with Solid Tumor, Adult and Mesothelioma, run by Vivace Therapeutics, Inc at 12 sites in 2 countries.
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 6 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Heather Fritz (650-627-7437, hfritz@inclin.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of Dose Limiting Toxicity (time frame: over the first 21 days of dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04665206, which also lists 1 linked publication.
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 2 Apr 2026.