Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors Enriched for Tumors With NF2 Gene Mutations
- Interventional
- Recruiting
- NCT04665206
Contact Information
Phase 1, Multi-Center, Open-Label, Study to Evaluate the Safety, Tolerability, and PK of VT3989 in Patients With Refractory Locally Advanced or Metastatic Solid Tumors Enriched for Tumors Harboring Mutations of the NF2 Gene
This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered 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.
Dose Escalation will employ a traditional 3 + 3 design to assess safety of VT3989 in patients
with refractory metastatic solid tumors or mesothelioma until until the MTD or recommended
phase 2 dose(s) and schedule(s) are determined. The recommended phase 2 dose(s) and
schedule(s) may be less than the MTD depending on the type and severity of AEs that occur
during and after the first cycle.
Dose Expansion patients will be enrolled into up to 4 cohorts: Cohorts 1 and 2 will both enroll mesothelioma patients with or without an NF2 mutation that have progressed following standard therapy. The cohorts will differ by either the dose and/or schedule of VT3989, as recommended by the SRC. If a 3rd expansion cohort for mesothelioma patients is enrolled, it will employ a different regimen than the initial 2 expansion cohorts. If an NF2m solid tumor cohort is evaluated, it will use one of the regimens evaluated in the mesothelioma expansion cohorts.
Dose Expansion patients will be enrolled into up to 4 cohorts: Cohorts 1 and 2 will both enroll mesothelioma patients with or without an NF2 mutation that have progressed following standard therapy. The cohorts will differ by either the dose and/or schedule of VT3989, as recommended by the SRC. If a 3rd expansion cohort for mesothelioma patients is enrolled, it will employ a different regimen than the initial 2 expansion cohorts. If an NF2m solid tumor cohort is evaluated, it will use one of the regimens evaluated in the mesothelioma expansion cohorts.
Gender
All
Age Group
18 Years and up
Accepting 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: 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. In the solid tumor cohort, pathologically diagnosed solid tumor with documented NF2 mutations.
- Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors (solid tumor expansion cohort) or modified RECIST v1.1 for malignant pleural mesothelioma.
- ECOG: 0-1
Exclusion Criteria:
- Active brain metastases
- History of leptomeningeal metastases
- Active or chronic, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- HIV positive or active Hepatitis B or Hepatitis C
- Clinically significant cardiovascular disease
- Additional active malignancy that may confound the assessment of the study endpoints
- Women who are pregnant or breastfeeding
- 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: 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. In the solid tumor cohort, pathologically diagnosed solid tumor with documented NF2 mutations.
- Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors (solid tumor expansion cohort) or modified RECIST v1.1 for malignant pleural mesothelioma.
- ECOG: 0-1
Exclusion Criteria:
- Active brain metastases
- History of leptomeningeal metastases
- Active or chronic, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- HIV positive or active Hepatitis B or Hepatitis C
- Clinically significant cardiovascular disease
- Additional active malignancy that may confound the assessment of the study endpoints
- Women who are pregnant or breastfeeding
- Mesothelioma
- Solid Tumors