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Intrathecal Dual Checkpoint Inhibitor (PD-1 and CTLA-4) in Combination With Pemetrexed for Leptomeningeal Metastasis

ConditionsLeptomeningeal MetastasisPemetrexedPD-1 InhibitorCTLA4Solid Tumors
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age21-75
SponsorGuangzhou Medical University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Patients with poor compliance or other reasons that were unsuitable for this study.

Trial design

Design model

Single group

Treatments tested in this trial

  • QL1706 (bispecific antibody targeting PD-1 and CLTA-4)

    Drug

    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)

    Drug

    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.

Treatment groups

34 Participants
are divided into 1 treatment group
Group A: Intrathecal Dual Checkpoint Inhibition in Combination with 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 months
2

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.

Secondary outcomes

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 months
2

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 months
3

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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Guangzhou Medical University

Lead sponsor

Source ClinicalTrials.gov
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