This multi-site Phase II study will enroll adults with histologically confirmed diagnosis of World Health Organization (WHO) Grade IV glioblastoma (GBM), isocitrate dehydrogenase (IDH)-wildtype consistent with WHO central nervous system (CNS) 2021 criteria who have received prior first-line treatment including with at least radiotherapy and temozolomide, with a Karnofsky performance status (KPS) ≥60, adequate organ function, and at least one measurable lesion according to the response assessment in neuro-oncology (RANO) 2.0 criteria.
Participants will be randomized to the two treatment Arms 1 and 2. After sponsor evaluation of the initial safety and efficacy signals from Arm 1, it will be determined whether to initiate Arm 3. Participants who have disease progression in Arm 2 may be eligible to receive pumitamig. There will be a screening period of up to 28 days, followed by a treatment period lasting up to 2 years. Participants will be followed-up for safety for up to 90 days after the last dose of study treatment or until the participant initiates new anticancer treatment (e.g., systemic, radiotherapy/surgery). Thereafter, survival follow-up will be conducted until the participant dies, the participant withdraws consent for survival status follow-up, loss of contact, or study termination (whichever occurs first).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
75
Beijing Tiantan Hospital, Capital Medical University
Beijing, China
RECRUITINGAffiliated Tumor Hospital of Chongqing Medical University
Chongqing, China
RECRUITINGAffiliated Cancer Hospital of Shandong First Medical University
Jinan, China
RECRUITINGHuashan Hospital, Fudan University
Shanghai, China
RECRUITINGShenzhen Second People's Hospital
Shenzhen, China
RECRUITINGUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China
RECRUITINGConfirmed overall response rate (ORR)
For Treatment Arms 1 and 2 only. Defined as the percentage of study participants in whom a confirmed complete response (CR) or confirmed partial response (PR) (assessed by the blinded independent central review \[BICR\] per RANO 2.0) is observed as best overall response.
Time frame: Up to 24 months
Occurrence of treatment emergent adverse events (TEAEs) by severity
According to (United States National Cancer Institute) Common Terminology Criteria for Adverse Events version 5.0 \[CTCAE v5.0\]). By relationship. For Treatment Arms 1 and 3 only.
Time frame: From the first dose of study treatment until 90 days after the last dose of study treatment (up to 27 months)
Occurrence of dose interruptions, reductions or discontinuations of study treatment due to TEAEs
For Treatment Arms 1 and 3 only.
Time frame: Up to 24 months
Confirmed ORR
Defined as the percentage of study participants in whom a confirmed CR or confirmed PR (assessed per RANO 2.0) is observed as best overall response. For Treatment Arms 1 and 2 assessment will be done by the investigator. For Treatment Arm 3, assessment will be done only by BICR.
Time frame: Up to 24 months
Progression free survival (PFS)
For Treatment Arms 1 and 2 only. Defined as the time from randomization to first documented tumor progression (progressive disease assessed by BICR and investigator per RANO 2.0) or death from any cause, whichever occurs first.
Time frame: Up to 24 months
PFS at 6 months
For Treatment Arms 1 and 2 only. Assessed by BICR and investigator per RANO 2.0.
Time frame: At 6 months from time of randomization
Duration of response
For Treatment Arms 1 and 2 only. Defined as the time from first objective response (CR or PR as assessed by BICR and investigator per RANO 2.0) to first occurrence of objective tumor progression (progressive disease as assessed by BICR and investigator per RANO 2.0), or death from any cause, whichever occurs first.
Time frame: Up to 24 months
Disease control rate
For Treatment Arms 1 and 2 only. Defined as the percentage of study participants in whom a confirmed CR or confirmed PR or stable disease (assessed by BICR and investigator per RANO 2.0) is observed as best overall response.
Time frame: Up to 24 months
Overall survival (OS)
For Treatment Arms 1 and 2 only. Defined as the time from participant randomization to death from any cause and at 6 and 12 months.
Time frame: Up to 42 months
OS rate
For Treatment Arms 1 and 2 only.
Time frame: At 6 and 12 months
Pharmacokinetic (PK) assessment: Maximum concentration (Cmax) of pumitamig
For Treatment Arms 1 and 3 only. As data permits.
Time frame: From the first dose of study treatment until 90 days after the last dose of study treatment (up to 27 months)
PK assessment: Minimum concentration (Cmin) of pumitamig
For Treatment Arms 1 and 3 only. As data permits.
Time frame: From the first dose of study treatment until 90 days after the last dose of study treatment (up to 27 months)
The prevalence and incidence of anti-pumitamig antibodies
For Treatment Arms 1 and 3 only. From before the first dose of study treatment until the last survival follow-up visit. ADA prevalence is the proportion of study participants with positive ADA against pumitamig at any point in time (baseline or post-baseline) during the study period. ADA incidence is the proportion of study participants with treatment-emergent ADA against pumitamig during the study period. Participants with treatment-emergent ADA includes study participants who were ADA negative or missing at baseline and became ADA positive post-baseline (treatment-induced ADA), and study participants who were ADA positive at baseline and post-baseline but had an increase in ADA titer of defined threshold from baseline to post-baseline (treatment-boosted ADA).
Time frame: Up to 27 months
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