Study of How Safe and Effective Tarlatamab is in Brain Cancers

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join if…

• 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 0-1.
• Patients must have a life expectancy ≥ 12 weeks.
• Patients of childbearing potential must have a negative serum pregnancy test within 28 days prior to start of therapy and Day 1 prior to start of therapy.
• All participants must agree to use 2 acceptable methods to prevent pregnancy for study required duration.
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• All patients in Cohort 1 and Cohort 2 are required to submit archival tissue. In addition,
• Patients in Cohort 1 must be willing to provide fresh tumor samples at the time of clinically indicated surgical resection/debulking, or willing to undergo post-treatment tumor biopsy.
• Patients in Cohort 2 must be willing to provide tumor samples should they require surgical resection/debulking or undergo clinically indicated tumor biopsy after enrollment in trial.
• Patients in Cohort 2 must have measurable and progressive disease documented within 28 days of start of study treatment
• Patients must be asymptomatic and meet the following criteria:
• At least 28 days after the most recent CNS treatment, clinically stable.
• At least 14 days on stable doses of corticosteroids and/or anti-seizure medications.

🚫 You may not be able to join if…

• 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.
• Patients with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of tarlatamab.
• Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV), or those who have had a solid organ transplant or allogeneic transplant.
• History of hypophysitis or pituitary dysfunction.
• Exclusion of hepatitis infection based on the following results and/or criteria (within 3 months prior to the first dose of tarlatamab):
• Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B).
• Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
• Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
• Whole blood transfusions within 120 days prior to enrollment to the study (packed red blood cells and platelet transfusions are acceptable outside of 28 days prior to treatment).
• Current or prior use of immunosuppressive medications within 14 days before the 1st dose of tarlatamab. Patients receiving systemic corticosteroids must have been on a stable dose of corticosteroids for at least 14 days prior to the 1st dose of tarlatamab.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, celiac disease, and Wegner syndrome) within the last 2 years. Patients with vitiligo, alopecia, Grave's disease, hypothyroidism stable on hormone replacement, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded.

+ 7 more criteria — see the full checklist in the app.

Where this trial is running

• Princess Margaret Cancer Centre, Toronto, Ontario, Canada

Who to contact

Eric Chen, MD · 416-946-2263 · eric.chen@uhn.ca

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT06776250.