Intrathecal PD-1/VEGF Bispecific Antibody Plus Pemetrexed for Leptomeningeal Metastasis
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age21-75
SponsorGuangzhou Medical University
About this trial
Leptomeningeal metastasis, characterized by tumor cells infiltrating and proliferating in the subarachnoid space, represents a distinct pattern of central nervous system involvement and is a fatal complication of malignant tumors.
This phase I/II study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal PD-1/VEGF bispecific antibody plus pemetrexed in patients with leptomeningeal metastasis.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically or cytologically confirmed diagnosis of solid tumors;Cerebrospinal fluid cytopathology is positive.
Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
No history of severe nervous system disease; No severe dyscrasia.
Disqualifiers
Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.
Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
Obvious bleeding tendency; Patients with hemorrhage (NCI-CTCAE v5.0 greater than grade 2), coagulation disorder, hypertensive crisis, and severe arterial thrombosis.
A history of HIV or AIDS, acute or chronic hepatitis B or C infection, previous anti-PD1 therapy-induced pneumonitis, or have ongoing >Grade 2 adverse events of such therapy; or ongoing autoimmune disease that required systemic treatment in the past 2 years.
Trial design
Design model
Single group
Treatments tested in this trial
AK112
DrugIntrathecal injection of PD-1/VEGF bispecific antibody was administered every two weeks for six weeks during the induction phase, followed by monthly injections during the maintenance phase, until recurrence or death.
Pemetrexed (Alimta)
DrugPemetrexed was administrated by intrathecal injection, first as induction therapy, twice per week for 2 weeks, followed by consolidation therapy, once per week for 4 weeks, then maintenance therapy, once per month until the patient's death, leptomeningeal metastasis progresses, or intolerable severe adverse events occurred.
Treatment groups
34 Participants
are divided into 1 treatment groupGroup A: Intrathecal PD-1/VEGF Bispecific Antibody plus PemetrexedExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
PR2D
The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity.
Time frame
From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months2
Incidence of treatment-related adverse events
The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE). Events of grade 3-5 are defined as moderate and severe adverse events.
Time frame
From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.Other outcomes
1
Clinical response rate
The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
Time frame
From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months2
Progression-free survival related to leptomeningeal metastasis (LMPFS)
LMPFS was defined as time from the start of treatment until leptomeningeal metastasis progression or death. The leptomeningeal metastasis progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.
Time frame
From date of treatment until the date of first documented leptomeningeal metastasis progression or date of death from any cause, whichever came first, assessed up to 6 months3
Overall survival(OS)
Overall survival was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
Time frame
From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up，assessed up to 6 months.Sponsors and contacts
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Source ClinicalTrials.gov