A Phase II Study Evaluating the Safety, Efficacy, and Intracranial Activity of Tarlatamab in Recurrent/Refractory Gliomas With IDH Mutation (TARGID)
Overview
- Phase
- Phase 2
- Intervention
- Tarlatamab
- Conditions
- Not specified
- Sponsor
- University Health Network, Toronto
- Enrollment
- 44
- Locations
- 1
- Primary Endpoint
- Percent change in CD8+ T cell infiltrate
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a phase 2 study to assess how useful study drug tarlatamab is for the treatment of patients with recurrent/refractory oligodendroglioma or astrocytoma with a mutation in the IDH gene.
Detailed Description
There will be 2 cohorts in the study. * Cohort 1, patients whose disease is amendable for resection will be treated with up to 3 cycles of tarlatamab prior to surgical resection. These patients can resume tarlatamab treatment post-operatively until disease progression at the discretion of the investigator. Up to 10 patients may be enrolled to Cohort 1. * Cohort 2, patients with progressive/refractory disease are eligible to receive tarlatamab at Q2W 10 mg dosing in 28 day cycles until documented disease progression, intolerable toxicity or consent withdrawal. The Simon's 2 stage design will be used. In stage 1, 13 patients will be enrolled. Based on an interim analysis of efficacy, stage 2 will aim to enroll an additional 21 patients for a total of 34 patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of informed consent prior to any study specific procedures.
- •Must be 18 years of age or older.
- •Body weight \> 40 kg.
- •Patients must have histologically or cytologically confirmed diffuse astrocytic or oligodendroglial tumors by World Health Organization 2016 classification which are IDH mutant.
- •Patients could have received up to 2 regimens of systemic therapy after relapse.
- •For Cohort 1: Patient must be clinically deemed resectable and a resection is clinically indicated.
- •For Cohort 2: Patient must be unresectable or a resection is not clinically indicated at the time of enrollment.
- •Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Patients must have a life expectancy ≥ 12 weeks.
Exclusion Criteria
- •Concurrent enrollment in another clinical study, unless it is an observational (non-intervention) clinical study or the follow-up period of an interventional study.
- •Receipt of any conventional or investigational anticancer therapy within 28 days prior to the first dose of tarlatamab.
- •Any previous treatment with tarlatamab.
- •Other malignancy within the last 5 years with exceptions.
- •Patients receiving any systemic chemotherapy or radiotherapy within 28 days prior to study treatment.
- •Unresolved toxicity from prior anti-tumor therapy or prior surgery.
- •Major surgery within 28 days of starting study treatment and patients must have recovered from any effects of any major surgery.
- •Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
- •History of arterial thrombosis within 12 months of first dose of tarlatamab.
- •Patients who are pregnant, lactating, or intend to become pregnant during their participation in this study.
Arms & Interventions
Cohort 1
Patients whose disease is amendable for resection will be treated with up to 3 cycles of tarlatamab prior to surgical resection. These patients can resume tarlatamab treatment post-operatively until disease progression at the discretion of the investigator. Up to 10 patients may be enrolled to Cohort 1.
Intervention: Tarlatamab
Cohort 2
Patients with progressive/refractory disease are eligible to receive tarlatamab at every 2 weeks 10 mg dosing in 28 day cycles until documented disease progression, intolerable toxicity or consent withdrawal. Up to 34 patients may be enrolled to Cohort 2.
Intervention: Tarlatamab
Outcomes
Primary Outcomes
Percent change in CD8+ T cell infiltrate
Time Frame: 3 years
Secondary Outcomes
- Percent change in CD3/CD45RA/RO T cells(3 years)
- Percent change in T cell subsets(3 years)
- Percentage change in M1 vs M2 macrophage populations(3 years)
- Tumour concentrations of tarlatamab(3 years)
- Serum concentrations of tarlatamab(3 years)