Tarlatamab for recurrent IDH‑mutant astrocytoma and oligodendroglioma

A Phase II Study Evaluating the Safety, Efficacy, and Intracranial Activity of Tarlatamab in Recurrent/Refractory Gliomas With IDH Mutation (TARGID)

This trial will try tarlatamab, an immune‑engaging drug, in adults with recurrent or refractory IDH‑mutant astrocytoma or oligodendroglioma to see if it shrinks tumors or slows progression.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Drugs / interventions: tarlatamab, chemotherapy
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06776250 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, interventional trial testing tarlatamab in two cohorts of adults with recurrent or refractory IDH‑mutant diffuse astrocytic or oligodendroglial tumors. Cohort 1 enrolls up to 10 patients who are amenable to surgical resection and receive up to three cycles of tarlatamab before surgery, with the option to resume post‑operative dosing. Cohort 2 uses a Simon two‑stage design to enroll up to 34 unresectable patients who receive 10 mg tarlatamab every two weeks in 28‑day cycles until progression, intolerable toxicity, or withdrawal. Safety, tumor response, and feasibility of pre‑operative dosing will be monitored throughout.

Who should consider this trial

Good fit: Adults (≥18 years) weighing >40 kg with histologically confirmed IDH‑mutant diffuse astrocytic or oligodendroglial tumors, ECOG 0–1, adequate organ and marrow function, life expectancy ≥12 weeks, and who meet cohort‑specific resectability criteria are eligible.

Not a fit: Patients with IDH‑wildtype tumors, poor organ or bone marrow function, ECOG >1, life expectancy <12 weeks, or who have received more than two prior post‑relapse systemic regimens are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, tarlatamab could provide a new targeted immunotherapy option that shrinks or delays growth of recurrent IDH‑mutant gliomas.

How similar studies have performed: Bispecific T‑cell engager approaches have shown activity in some other cancers, but using tarlatamab specifically for IDH‑mutant brain tumors is a novel approach with limited prior data.

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 0-1.
* 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.

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.
* 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.
* Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational products or interpretation of patient safety or study results.
* Receipt of live attenuated vaccines within 30 days prior to the 1st dose of tarlatamab, during the study and for 30 days after the last dose of tarlatamab. Examples include, but are not limited to, vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal), chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG vaccine, typhoid vaccine and typhus vaccine.
* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice).
* History of allergic reaction attributed to compounds of similar chemical or biologic composition to tarlatamab.
* Patients unable to remain within one hour of study site for additional 48 hours after hospitalization on cycle 1 day 1 and cycle 1 day 8.
* Patients unable to remain within one hour of any hospital for 72 hours after infusion of tarlatamab on cycle 1 day 1 and cycle 1 day 8.
* Patients unable to identify home companion who will cohabitate with subject for 72 hours after infusion of tarlatamab on cycle 1 day 1 and cycle 1 day 8.

Where this trial is running

Toronto, Ontario

• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Eric Chen, MD — Princess Margaret Cancer Centre/University Health Network
• Study coordinator: Eric Chen, MD

Conditions Astrocytic Tumor; Oligodendroglial Tumor