Study to Evaluate VT3989 in Patients with Metastatic Solid Tumors
- Conditions
- Solid Tumor, AdultMesotheliomaNSCLC
- Interventions
- Registration Number
- NCT04665206
- Lead Sponsor
- Vivace Therapeutics, Inc
- Brief 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 3- or 4-week cycles in patients with mesothelioma and/or metastatic solid tumors that are resistant or refractory 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 refractory 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 two 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 336
- Part 1: pathologically diagnosed metastatic solid tumor or mesothelioma that has progressed on or after all approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy;
- Part 2 Expansion Cohorts 1 and 2: in mesothelioma cohorts, pathologically diagnosed advanced malignant mesothelioma with or without NF2 mutations, that has progressed on or after all approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy.
- Part 2 Expansion Cohort 3: non-pleural mesothelioma patients with epithelioid histology, relapsed from or refractory to prior platinum-based chemotherapy and immunotherapy.
- Part 2 Expansion Cohort 4: in the solid tumor cohort, pathologically diagnosed metastatic or locally advanced solid tumor with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements, which have progressed on or after approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy.
- Part 2 Expansion Cohort 5: pathologically diagnosed advanced malignant pleural mesothelioma with epithelioid histology, that has progressed on or after licensed immunotherapy, chemotherapy or combined chemoimmunotherapy except if the patient refuses or is not a candidate for such therapy.
- Part 3 Combination Cohort A: pathologically diagnosed, metastatic or unresectable malignant mesothelioma including both pleural and non-pleural) patients who have not received systemic therapy.
- Part 3 Combination Cohort B: 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 1: evaluable or measurable disease per RECIST v1.1 or mRECIST
- Part 2 and 3: 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
- 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
- Corrected QT (QTcF) interval > 470 msec (using Fridericia's correction formula); except for Part 2 Expansion Cohort 3, the QTcF interval criteria is > 450 msec)
- Additional active malignancy that may confound the assessment of the study endpoints
- Women who are pregnant or breastfeeding
- Prior treatment with TEAD inhibitor, except for EHE patients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description VT3989 Dose Escalation VT3989 VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase Dose Expansion VT3989 VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma. Combination VT3989 VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib) Combination Nivolumab & Ipilimumab VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib) Combination Osimertinib VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib)
- Primary Outcome Measures
Name Time Method Occurrence of General Toxicity through study completion, an average of 30 months Incidence of Adverse and Serious Adverse Events, Discontinuations due to Adverse Events and general safety Evaluations
Occurrence of Dose Limiting Toxicity over the first 21 days of dosing Incidence of Adverse and Serious Adverse Events
- Secondary Outcome Measures
Name Time Method Tumor Response through study completion, an average of 30 months Determined by RECIST v1.1 or modified RECIST v1.1
Pharmacokinetic Evaluation - Cmax for first 6 cycles Peak plasma concentration of VT3989
Pharmacokinetic Evaluation - Tmax for first 6 cycles Time to reach peak plasma concentration of VT3989
Pharmacokinetic Evaluation - Half-life for first 6 cycles Time required for the plasma concentration of VT3989 to reduce by half after reaching peak
Overall survival (Part 2, expansion cohort 3 only) Through study completion, an average of 30 months The overall survival of the enrolled patients from starting VT3989 treatment
Progression free survival (Part 2, expansion cohort 3 only) Through study completion, an average of 30 months The progression free survival of the enrolled patients from starting VT3989 treatment
Quality of life assessment (Part 2, expansion cohort 3 only) Through study completion, an average of 30 months Assessing the Quality of life changes via patient reported outcomes
Trial Locations
- Locations (10)
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
M Health Fairview University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
Memorial Sloan Kettering Cancer Center-
🇺🇸New York, New York, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Monash Health
🇦🇺Clayton, Victoria, Australia
Peter MacCullum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia