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

Phase 1

Not yet recruiting

• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

• Registration Number: NCT06586294
• Lead Sponsor: Akeso

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-04
• Study First Submitted QC: 2024-09-04
• Last Update Submitted: 2024-09-04
• Study First Posted: 2024-09-06
• Last Update Posted: 2024-09-06
• Study Start: 2024-09-10
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 294

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Incidence and severity of adverse events(AE)	Up to approximately 2 years	Incidence and severity of AEs is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab
Incidence of serious adverse events(SAE) and suspected unexpected serious adverse reactions(SUSAR)	Up to approximately 2 years	Incidence of SAE and SUSAR is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab
Incidence of dose-limiting toxicity(DLT)	Up to approximately 2 years	The purpose of DLT is to find the Phase II recommended dose(RP2D) or Maximum Tolerated Dose(MTD)
Clinically significant changes in safety/laboratory evaluation parameters and AEs that led to treatment termination or suspension	Up to approximately 2 years	Clinically significant changes in safety/laboratory evaluation parameters and AEs that led to treatment termination or suspension is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab
Objective Solution Rate (ORR) based on RECIST v1.1	Up to approximately 2 years	The purpose of ORR is aim to evaluate the antitumor effect,and ORR is proportion of subjects with complete response(CR) or partial response(PR), based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1.

Secondary Outcome Measures

Name	Time	Method
Disease control rate(DCR)	Up to approximately 2 years	Disease control rate(DCR) is defined as the proportion of subjects achieving a best of response(BOR) of confirmed CR or PR or stable disease(SD) per RECIST v1.1.
duration of response(DoR)	Up to approximately 2 years	Duration of response(DoR) is defined as the period from the first documentation of confirmed response(CR or PR) to the first documentation of progressive disease(PD) as per RECIST v1.1 or death due to any cause, whichever occurs first.
time to response(TTR)	Up to approximately 2 years	Time to response(TTR) is defined as the time from the first dose of investigational products until the first confirmation of CR or PR.
progression-free survival(PFS)	Up to approximately 2 years	Progression-free survival(PFS) is defined as the time from the first dose of investigational products until documentation of progressive disease(PD) as per RECIST v1.1 or death due to any cause, whichever occurs first.
overall survival(OS)	Up to approximately 2 years	Overall survival(OS) is defined as the time from the first dose of investigational products until death due to any cause.
Serum AK129, cadonilimab concentration, blood concentration-time curve and derived PK argument	Up to approximately 2 years	Serum AK129, cadonilimab concentration, blood concentration-time curve and derived PK argument to evaluate the Pharmacokinetics(PK).
Number and percentage of subjects with anti-drug antibodies (ADA) for AK129 and cadonilimab	Up to approximately 2 years	Number and percentage of subjects with anti-drug antibodies (ADA) for AK129 and cadonilimab will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Trial Locations

Locations (1)

Zhejiang Cancer Hospital; 🇨🇳 Hanzhou, Zhejiang, China