Mesothelioma, Pleural Mesothelioma
Conditions
Keywords
Mesothelioma
Brief summary
This randomized, open-label, multicenter Phase 3 trial will compare VT3989 with Investigator's choice of gemcitabine or vinorelbine in adults with advanced epithelioid pleural mesothelioma whose disease progressed after prior platinum-based systemic chemotherapy and immunotherapy.
Detailed description
Approximately 350 participants will be randomized 1:1 to VT3989 (Arm A) or Investigator's choice chemotherapy with gemcitabine or vinorelbine (Arm B). VT3989 will be administered orally at 100 mg once daily for 2 weeks on treatment followed by 2 weeks off treatment in each 4-week cycle. Comparator treatment will be gemcitabine or vinorelbine using the protocol-specified regimen or local prescribing/institutional practice. The trial includes screening, treatment, safety follow-up, and survival follow-up periods. A QTc Sub-Study will evaluate cardiac repolarization using time-matched pharmacokinetic samples and ECGs in approximately 25 Arm A participants. Overall survival is the primary endpoint; BICR-assessed progression-free survival is the key secondary endpoint.
Interventions
DRUGVT3989
• 100 mg orally once daily for 2 weeks on treatment followed by 2 weeks off treatment (2W/2W) in each 4-week cycle
DRUGgemcitabine
• 1,000 mg/m2 IV on Days 1 and 8 of each 3-week cycle, or per local prescribing information/institutional practice
DRUGVinorelbine
• 25-30 mg/m2 IV on Days 1 and 8 of each 3-week cycle, or per local prescribing information/institutional practice
Sponsors
Vivace Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomized 1:1 to VT3989 or Investigator's choice chemotherapy (gemcitabine or vinorelbine).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, age 18 years or older at informed consent. * Pathologically confirmed advanced epithelioid pleural mesothelioma previously treated with platinum-based systemic chemotherapy and immunotherapy, given sequentially or concurrently. * Radiologically measurable disease by modified RECIST v1.1 or RECIST v1.1. * 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 and prior exposure to cardiotoxic agents * Corrected QT (QTcF) interval \> 470 msec (using Fridericia's correction formula). * Women who are pregnant or breastfeeding * Non-pleural mesothelioma at initial diagnosis or an aggressive histologic type such as sarcomatoid or biphasic mesothelioma. * Prior treatment with a TEAD inhibitor, including VT3989 or another agent targeting the same molecular pathway. * Prior receipt of both comparator treatments, gemcitabine and vinorelbine, alone or in combination, or known hypersensitivity to both. A participant who received only one comparator may enroll but must not be assigned to that same comparator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately 32-35 months after first randomization | Time from randomization to death from any cause. Participants without an observed death will be censored at the last date known alive or the analysis cut-off date, whichever is earlier. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival by BICR | From randomization through radiologic progression, death, up to approximately 3 years or more | Time from randomization to the first BICR-assessed radiologic progressive disease or death, using protocol-defined censoring rules. |
| Treatment-Emergent Adverse Events and Serious Adverse Events | From first dose through the safety follow-up visit, (28 days after the last dose), up to approximately 3 years or more. | Incidence and severity of Treatment-Emergent Adverse Events and Serious Adverse Events |
| Disease-related symptoms and health-related quality of life outcomes | Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more | Disease-related symptoms, treatment side effects, functioning, and health-related quality of life outcomes and time to deterioration. |
| Overall Response Rate by BICR | Tumor assessments during treatment and applicable follow-up; up to approximately 3 years or more | Overall Response Rate by BICR Proportion with best overall response of complete response or partial response by RECIST v1.1 and/or modified RECIST v1.1, assessed by BICR. |
| Duration of Response | From first documented response through progression, death, or analysis cut-off; up to approximately 3 years or more | Among participants with a complete or partial response, time from first documented response to progressive disease or death, with protocol-defined censoring. |
| Disease Control Rate by BICR | Tumor assessments during treatment and applicable follow-up; up to approximately 3 years or more | Proportion with best overall response of complete response, partial response, or stable disease by RECIST v1.1 and/or modified RECIST v1.1, assessed by BICR. |
| Time to Response | From randomization to first documented response; up to approximately 3 years or more | Time from randomization to the first documented complete or partial response by RECIST v1.1 and/or modified RECIST v1.1. |
| EORTC QLQ-LC13 | Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more | Lung cancer- and treatment-related symptoms using the EORTC Quality of Life Questionnaire Lung Cancer Module 13. |
| EQ-5D-5L | Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more | Health status and health-related quality of life using the EuroQol 5 Dimension-5 Levels instrument. |
| Time to Deterioration | From baseline/randomization through protocol-defined deterioration; up to approximately 3 years or more | Time to protocol-defined deterioration in disease-related symptoms and health-related quality of life; detailed definition will be specified in the Statistical Analysis Plan. |
Contacts
CONTACTArick Wong
CONTACTDereck Amakye
Outcome results
None listed