Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Conditions
Brief summary
This is a multicenter, randomized, controlled, open-label, Phase III study, designed to evaluate the efficacy and safety of JS107 versus investigator-selected therapy in the second-line or later treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma positive for CLDN18.2. The study population consists of patients with CLDN18.2-positive, HER2-negative, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma who have received at least one prior line of systemic therapy. The primary endpoints of the study are BICR-assessed progression-free survival and overall survival. Number of subjects and allocation:This study plans to enroll approximately 560 subjects, who will be randomized in a 1:1 ratio to receive either JS107 (experimental group) or investigator-selected therapy (control group).
Detailed description
Patients with HER2 negative G/GEJ adenocarcinoma confirmed by histology/cytology. who have received at one prior line of systemic treatment and developed PD, and the previous treatment must include fluorouracil and platinum; CLDN18.2-positive, HER2-negative.
Interventions
DRUGJS107 for Injection
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).
DRUGIrinotecan
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).
DRUGPaclitaxel
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).
DRUGDocetaxel
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily participate in this study, have ICF signed after sufficient informed consent, and have good compliance. 2. Age ≥ 18 years, male or female. 3. ECOG PS 0 or 1. 4. Expected survival period≥ 3 months. 5. Patients with HER2 negative G/GEJ adenocarcinoma confirmed by histology/cytology. 6. Patients who have received at least one prior line of systemic treatments and developed PD, and the previous treatment must include fluorouracil and platinum. 7. Fresh or archival tumor tissue (blocks of formalin-fixed, paraffin-embedded \[FFPE\] tissue or unstained FFPE tumor tissue sections) must be available and comfirmed CLDN18.2 positivity by for central laboratory through immunohistochemistry (IHC) before randomization. 8. Having ≥ 1 measurable lesion according to RECIST v1.1 (per investigator assessment). 9. Any AEs and/or complications caused by previous therapies including surgery or radiotherapy have been adequately resolved to Grade 0 or 1 (per NCI-CTCAE v5.0 criteria) or have been stabilized in the judgment of investigators.
Exclusion criteria
1. Previous treatment with any drug or cellular therapy targeting CLDN18.2 (except CLDN18.2 monotarget monoclonal antibody). 2. Previously treated with an ADC loaded with a tubulin inhibitor. 3. Received strong CYP3A inhibitor or inducer within 2 weeks or 5 half-lives prior to randomization, whichever is longer. 4. Use of chemotherapy, immunotherapy or other anti-tumor therapies or participation in other clinical trials within 3 weeks prior to randomization, or use of oral fluorouracil, small molecule targeted drugs or traditional Chinese medicine for gastric cancer within 2 weeks prior to randomization. 5. Major surgery (requiring general anaesthesia and \>24 hours of Hospitalisation) or other clincal trial drug treatment within 4 weeks prior to randomization, or radiotherapy within 2 weeks prior to randomization. 6. Imaging demonstrating brain metastases (except patients who have completed whole brain radiotherapy or local therapy (such as surgery), have discontinued prednisone for at least 4 weeks prior to randomization, and have stable radiologically confirmed tumor lesions and no clinical symptoms of tumor during 4 weeks prior to randomization), metastases to meninges, or spinal cord compression. 7. Tumor invades important surrounding structures (e.g., large blood vessels, trachea, etc.) with high risk of rupture and hemorrhage or airway fistula, or metastases to bone with high risk of paraplegia. 8. Thromboembolic events within 3 months prior to randomization (except patients with non-pulmonary Thromboembolism who do not require treatment or have been stably treated with anticoagulants for 14 days or longer prior to randomization). 9. History of other neoplasm malignant within 5 years prior to randomization, except for neoplasm malignant cured after treatment. 10. Having active autoimmune diseases requiring systemic treatment (i.e., immunologic modulator, corticosteroid, or Immunosuppression) within 2 years prior to randomization; replacement therapy (such as thyroid hormone, Insulin, or physiologic corticosteroid replacement therapy due to adrenal or pituitary insufficiency) is not considered systemic treatment. 11. Known severe allergic reaction to any component in the investigational drug formula.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BICR-PFS | up to 2 years | Progression-Free Survival (BICR-PFS) evaluated based on Blinded Independent Central Review (BICR) (according to the RECIST v1.1 criteria) |
| Overall Survival | up to 5 years | The primary endpoint of overall survival (OS) in this multicenter, randomized, open-label Phase III study is the time from randomization to death from any cause, aiming to compare the benefit between JS107 and investigator's choice of therapy in patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma who have received at least one prior line of systemic therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| INV-PFS | up to 2 years | Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria) |
| BICR-ORR or INV-ORR | up to 2 years | ORR evaluated by investigators or BICR (according to the RECIST v1.1 criteria) |
| BICR-DCR or INV -DCR | up to 2 years | Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria) |
| BICR-DoR or INV -DoR | up to 2 years | DoR (based on the RECIST v1.1 criteria) evaluated by investigators or BICR |
| The incidence rate and severity of AE | up to 2 years | The incidence and severity of adverse events (AEs) evaluated according to the NCI-CTC AE v5.0 standard |
| Valley concentration of JS107 | up to 2 years | Valley concentration of JS107 (including ADC, total antibody, and toxin) |
| anti-drug antibodies (ADA) for JS107 | up to 2 years | Incidence and titer of anti-drug antibodies (ADA) for JS107 (including ADC, total antibody, and toxin) |
| Incidence of neutralizing antibodies (NAb) to JS107 | up to 2 years | Incidence of neutralizing antibodies (NAb) to JS107 (including ADC, total antibody, and toxin) |
Countries
China
Contacts
CONTACTYongdong Zhang
Outcome results
None listed