LM-108 plus toripalimab versus paclitaxel for CCR8-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma

A Phase III, Open-Label, Multicenter, Randomized, Parallel-Group Study to Evaluate the Efficacy and Safety of LM-108 in Combination With Toripalimab Versus Paclitaxel Injection as Second-Line Therapy for CCR8-Positive Locally Advanced or Metastatic Gastric Cancer/Gastroesophageal Junction Adenocarcinoma

This trial tests whether adding LM-108 (an anti-CCR8 antibody) to the PD-1 blocker toripalimab works better than paclitaxel for adults with CCR8-positive advanced or metastatic gastric or GEJ adenocarcinoma after first-line therapy.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: LaNova Medicines Limited (industry)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, Toripalimab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07362186 on ClinicalTrials.gov

What this trial studies

This phase III, multicenter, randomized trial compares the combination of LM-108 and toripalimab to standard paclitaxel chemotherapy in patients with CCR8-positive, HER2-negative or low-expressing locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. Eligible patients must have progressed on or been intolerant to prior first-line therapy, have at least one measurable lesion, ECOG performance status 0–1, and adequate organ function; CCR8 status is confirmed by a central lab. The primary goals are to measure efficacy (such as response and survival endpoints) and safety of the combination versus paclitaxel. Patients will receive intravenous infusions per the assigned arm and be followed for tumor response, adverse events, and survival.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed locally advanced or metastatic gastric or GEJ adenocarcinoma who are CCR8-positive, HER2-negative/low, have progressed on or are intolerant to first-line therapy, have ECOG 0–1, at least one lesion, and adequate organ and marrow function are ideal candidates.

Not a fit: Patients who are CCR8-negative, HER2-positive, eligible for curative surgery or radiotherapy, have ECOG ≥2, poor organ function, or cannot travel to the trial site are unlikely to benefit from enrolling.

Why it matters

Potential benefit: If successful, this regimen could provide better tumor control and longer survival than standard paclitaxel for patients with CCR8-positive advanced gastric/GEJ cancer and may offer a more targeted immunotherapy option.

How similar studies have performed: PD-1 inhibitors like toripalimab have shown activity in gastric cancer, and targeting tumor-regulatory cells is an emerging approach, but direct clinical evidence for CCR8-targeting antibodies remains limited and largely investigational.

Eligibility criteria

Inclusion Criteria:

1. Individuals who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
2. Age 18 years or older, male or female.
3. Weight ≥ 40 kg or Body Mass Index (BMI)≥ 18.5 kg/m²
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Life expectancy ≥ 3 months.
6. Individuals must have histologically or cytologically confirmed locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma and be ineligible for curative surgery or radiotherapy.
7. Confirmed CCR8-positive by the central laboratory.
8. HER2-negative, low-expressing, or non-expressing.
9. Individuals must experience radiographic progression during or after prior standard first-line therapy, or who developed intolerance to treatment due to chemotherapy-related toxicity
10. At least one lesion.
11. Have appropriate organ and marrow function in laboratory examinations.
12. Women of childbearing potential have a negative pregnancy test and must not be breastfeeding. All of reproductive potential agree to use effective contraception throughout the study period and for 6 months after the last dose of study drug.

Exclusion Criteria:

1. Received treatment targeting the same target or other drugs acting on regulatory T cells (Tregs).
2. Received antitumor treatments such as chemotherapy, radiotherapy, biological therapy, immunotherapy, or Chinese herbal medicine or Chinese herbal preparations within 2-4 weeks (depending on the specific anticancer drug) prior to the first dose.
3. Received anti-PD-(L)1 antibody immunotherapy and experienced disease progression confirmed by RECIST 1.1 assessment within ≤2 months after treatment initiation.
4. Use of any live vaccine within 4 weeks prior to the first dosing of study drugs.
5. Individuals who received major surgery or interventional treatment within 4 weeks prior to the first dosing of study drugs.
6. Individuals who take systemic corticosteroids (\> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications within 2 weeks prior to the first dosing of study drugs.
7. Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v6.0, individuals who experienced ≥ Grade 3 immune-related adverse events during prior immunotherapy, or terminated prior immunotherapy due to severe or life-threatening immune-related adverse events.
8. Any other pathological type.
9. Uncontrollable clinical third-space fluid accumulation.
10. Unstable or progressive central nervous system (CNS) metastases or carcinomatous meningitis (meningeal metastases).
11. Individuals with a known history of autoimmune diseases.
12. For individuals with drug allergies or contraindications.
13. The investigator determined that there are other situations that are not suitable for participation in this study.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Lin Shen — Peking University Cancer Hospital & Institute
• Study coordinator: Mengmeng Liu

Conditions: Locally Advanced or Metastatic GC and GCJ Adenocarcinoma