Study to Evaluate VT3989 in Patients with Metastatic Solid Tumors
Purpose
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.
Conditions
- Solid Tumor, Adult
- Mesothelioma
- NSCLC
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
Exclusion Criteria
- 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
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Part 1 dose escalation: 3 + 3 design Part 2 dose expansion: up to 6 cohorts Part 3 combination: 2 cohorts
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental VT3989 Dose Escalation |
VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase |
|
|
Experimental Dose Expansion |
VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma. |
|
|
Experimental Combination |
VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib) |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Vivace Therapeutics, Inc
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).