Leptomeningeal MetastasisPhase 1/2NCT06809530
Intrathecal Dual Checkpoint Inhibitor (PD-1 and CTLA-4) in Combination With Pemetrexed for Leptomeningeal Metastasis
A Phase 1/2 study testing QL1706 (bispecific antibody targeting PD-1 and CLTA-4) and Pemetrexed (Alimta) in people with Leptomeningeal Metastasis and Pemetrexed, run by Guangzhou Medical University at 5 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Leptomeningeal Metastasis, Pemetrexed, PD-1 Inhibitor
- What is being tested?
- QL1706 (bispecific antibody targeting PD-1 and CLTA-4) and Pemetrexed (Alimta)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 5 sitesChina
- Study dates
- 17 Mar 2025to 1 Sep 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine
Beijing, Beijing Municipality
Beijing Chest Hospital, Capital Medical University
Beijing, 101100
The Affiliated Huizhou Hospital, Guangzhou Medical University
Huizhou, Guangdong, 516000
Huizhou First Hospital Affiliated to Guangdong Medical University
Huizhou, Guangdong
Jinshan Hospital, Fudan University
Shanghai
About this study
Official title: Intrathecal Administration of Dual Checkpoint Inhibitor in Combination With Pemetrexed in Patients With Leptomeningeal Metastasis: a Phase I/II Study
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.
Read the 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.
- Conditions
- Leptomeningeal Metastasis, Pemetrexed, PD-1 Inhibitor, CTLA4, Solid Tumors
- Being tested
- QL1706 (bispecific antibody targeting PD-1 and CLTA-4), Pemetrexed (Alimta)
- Keywords
- Leptomeningeal metastasis, dual checkpoint inhibitor, pemetrexed
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal Dual Checkpoint Inhibition in Combination with Pemetrexed | Experimental | This study is a prospective, single-arm, Phase I/II clinical trial. The primary objectives were to determine the recommended dose of intrathecal dual checkpoint inhibitor (PD-1 and CTLA-4, QL1706) in combination with pemetrexed and safety based on the incidence of treatment-related adverse events. Clinical response rate (CRR), disease control rate (DCR) and overall survival (OS) are also evaluated. Patients will have cerebrospinal fluid (CSF) and blood specimen collection for the evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen. Receives: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4); Drug: Pemetrexed (Alimta) |
What is being measured
The primary outcome is the main question the study is designed to answer.
RP2D
The recommended phase II dose. The dose limiting toxicity was defined as ≥ grade 3 neurological toxicities (e.g.,meningitis) or other grade 4 toxicity.
Measured: Dose limiting toxicity was assessed during the first 6 weeks after the first intrathecal administration.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2025
- Study start17 Mar 2025
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhenyu Pan, Guangzhou Medical University
- Investigators
- Zhenyu Pan, PhD,MD, Principal investigator, Jinshan Hospital Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06809530
- Sponsor's protocol ID
- IT-P-QL1706
- Status last verified
- Jul 2026
- First submitted
- 26 Jan 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No