Clinical trial NCT06586294: A Study of Anti-PD-1 and LAG-3 Bispecific Antibody(AK129) Combined With Chemotherapy With or Without Cadonilimab in the First-line Treatment of Unresectable Locally Advanced or Metastatic G/ GEJ Adenocarcinoma
Official title: A Phase Ib/II Open Label,Dose Escalation and Dose Extension Study Evaluating the Safety, Tolerability, and Initial Antitumor Efficacy of Anti-PD-1 and Lymphocyte Activation Gene 3(LAG-3) Bispecific Antibody AK129 Combined With Chemotherapy With or Without Cadonilimab in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Negative Unresectable Locally Advanced or Metastatic G/GEJ Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1b/II, open-label, 2-part, multicenter, non-randomized, multiple-dose study
Primary purpose: TREATMENT

Brief summary: Phase Ib/II clinical study of AK129 combined with chemotherapy with or without cadonilimab in first-line treatment of advanced HER2 negative gastric cancer or gastroesophageal junction adenocarcinoma


Eligibility criteria: Inclusion Criteria:

1. The subject must sign the written informed consent form(ICF) voluntarily.
2. Aged ≥ 18 to ≤ 75 years,male and female at the time of signing the ICF.
3. Histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction (GEJ).
4. Inoperable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
5. Participants had not previously received systemic therapy for locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
6. According to RECIST v1.1 criteria, subjects had at least one measurable tumor target.

Exclusion Criteria:

1. Subjects with known HER2 positive gastric or gastroesophageal junction adenocarcinoma.
2. Histopathological examination confirmed other pathological types.
3. Had received palliative local therapy for non-target lesions within 2 weeks before the first administration.
4. Past treatment with immune checkpoint inhibitors,immune checkpoint agonists,immune cell therapy and any treatment targeting the immune mechanism of tumor action.
5. History of gastrointestinal perforation and fistula within 6 months before the first dose.
6. Active or previously documented inflammatory bowel disease,inability to swallow, malabsorption syndrome.
7. Active malignancy within the last 3 years.
8. Active or untreated brain metastases, meningeal metastases, spinal cord compression, or pia meningeal disease are known to exist.
9. The presence of clinical symptoms of pleural effusion, pericardial effusion, or abdominal effusion, or the need for frequent drainage.
10. There was an active autoimmune disease that required systemic treatment within 2 years prior to the start of the study.

Primary outcomes:
measure: Incidence and severity of adverse events(AE)
timeFrame: Up to approximately 2 years
measure: Incidence of serious adverse events(SAE) and suspected unexpected serious adverse reactions(SUSAR)
timeFrame: Up to approximately 2 years
measure: Incidence of dose-limiting toxicity(DLT)
timeFrame: Up to approximately 2 years
measure: Clinically significant changes in safety/laboratory evaluation parameters and AEs that led to treatment termination or suspension
timeFrame: Up to approximately 2 years
measure: Objective Solution Rate (ORR) based on RECIST v1.1
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Disease control rate(DCR)
timeFrame: Up to approximately 2 years
measure: duration of response(DoR)
timeFrame: Up to approximately 2 years
measure: time to response(TTR)
timeFrame: Up to approximately 2 years
measure: progression-free survival(PFS)
timeFrame: Up to approximately 2 years
measure: overall survival(OS)
timeFrame: Up to approximately 2 years
measure: Serum AK129, cadonilimab concentration, blood concentration-time curve and derived PK argument
timeFrame: Up to approximately 2 years
measure: Number and percentage of subjects with anti-drug antibodies (ADA) for AK129 and cadonilimab
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Zhejiang Cancer Hospital
name: Xiangdong Cheng, MD
role: PRINCIPAL_INVESTIGATOR
References: