Leptomeningeal Metastasis, Pemetrexed, PD-1 Inhibitor, CTLA4, Solid Tumors
Conditions
Keywords
Leptomeningeal metastasis, dual checkpoint inhibitor, pemetrexed
Brief summary
This phase I/II study is to evaluate the recommended dose, safety, feasibility, and therapeutic response of intrathecal dual checkpoint inhibitor (targeting PD-1 and CTLA-4 with QL1706) in combination with pemetrexed in patients with leptomeningeal metastasis.
Detailed description
This study is a prospective, single-arm, phase I/II clinical trial evaluating intrathecal dual checkpoint inhibitor (targeting PD-1 and CTLA-4 with the bispecific antibody QL1706) in combination with pemetrexed for the treatment of leptomeningeal metastasis. Intrathecal pemetrexed is administered twice weekly for 2 weeks (induction phase), then weekly for 4 weeks (consolidation phase), and monthly thereafter (maintenance phase). Intrathecal QL1706 (a co-formulation of separate anti-PD-1 and anti-CTLA-4 antibodies) is given every two weeks during the six-week （induction and consolidation phase）, followed by monthly injections in the maintenance phase, until disease progression or death. The primary objectives are to determine the recommended dose of intrathecal QL1706 in combination with pemetrexed and to assess safety based on the incidence of treatment-related adverse events. Clinical response rate, disease control rate, and overall survival are also evaluated. Patients undergo cerebrospinal fluid and blood specimen collection to evaluate potential clinical, molecular, and/or immune predictors of treatment efficacy and safety.
Interventions
Intrathecal injection of PD-1/CTLA-4 bispecific antibody was administered every 2 weeks for 6 weeks during the induction phase, followed by monthly injections during the maintenance phase, until recurrence or death.
Pemetrexed (Alimta, Eli Lilly and Company) 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.
Sponsors
Guangzhou Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of solid tumors; Cerebrospinal fluid cytopathology is positive. 2. Male or female aged between 21 and 75 years; Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3. 3. No history of severe nervous system disease; No severe dyscrasia.
Exclusion criteria
1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11. 2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment. 3. 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. 4. Patients with poor compliance or other reasons that were unsuitable for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP2D | Dose limiting toxicity was assessed during the first 6 weeks after the first intrathecal administration. | The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g.,meningitis) or other grade 4 toxicity. |
| Incidence of treatment-related adverse events | 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. | 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORZhenyu Pan, PhD,MD
Jinshan Hospital Fudan University
Outcome results
None listed