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

NCT06586294 | Not Yet Recruiting Phase 1

• 1 other identifier: AK129-103
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 1

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

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (5)

• Incidence and severity of adverse events(AE)

  Incidence and severity of AEs is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab

  Up to approximately 2 years

• Incidence of serious adverse events(SAE) and suspected unexpected serious adverse reactions(SUSAR)

  Incidence of SAE and SUSAR is aim to evaluate the safety of AK129 combined with chemotherapy with or without cadonilimab

  Up to approximately 2 years

• Incidence of dose-limiting toxicity(DLT)

  The purpose of DLT is to find the Phase II recommended dose(RP2D) or Maximum Tolerated Dose(MTD)

  Up to approximately 2 years

• Clinically significant changes in safety/laboratory evaluation parameters and AEs that led to treatment termination or suspension

  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

  Up to approximately 2 years

• Objective Solution Rate (ORR) based on RECIST v1.1

  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.

  Up to approximately 2 years

Secondary Outcomes (7)

• Disease control rate(DCR)

  Up to approximately 2 years

• duration of response(DoR)

  Up to approximately 2 years

• time to response(TTR)

  Up to approximately 2 years

• progression-free survival(PFS)

  Up to approximately 2 years

• overall survival(OS)

  Up to approximately 2 years

Study Arms (2)

The dose escalation and expansion stage of AK129 combined with chemotherapy;

EXPERIMENTAL

Part 1: The dose escalation stage： 3 dose groups of AK129 were set up, combination with chemotherapy of XELOX,followed by AK129 and capecitabine maintenance; Part 2：The dose expansion stage： Two to three dosing regimens were set for expansion of AK129 in combination with XELOX.

Drug: Drug: AK129 Drug：oxaliplatin Drug：capecitabine

The dose escalation and expansion stage of AK129 combined with chemotherapy with cadonilimab

EXPERIMENTAL

Part 1:The dose escalation stage： 3 dose groups of AK129 were set up, combination with cadonilimab and chemotherapy of XELOX,followed by AK129 and cadonilimab maintenance; Part 2:The dose expansion stage： Two to three dosing regimens were set for expansion of AK129 in combination with cadonilimab and chemotherapy of XELOX.

Drug: Drug: AK129 Drug：cadonilimab Drug：oxaliplatin Drug：capecitabine

Interventions

Drug: AK129 Drug：oxaliplatin Drug：capecitabine DRUG

AK129 is administered intravenously according to the frequency every three weeks(Q3W) and different dosage of administration at different stages.Oxaliplatin is administered intravenously according to the frequency and dosage 130 mg/m2 on day 1 Q3W.Capecitabine is administered intravenously according to the frequency and dosage 1000 mg/m2 oral twice daily on day 1 to 14 Q3W.

The dose escalation and expansion stage of AK129 combined with chemotherapy;

Drug: AK129 Drug：cadonilimab Drug：oxaliplatin Drug：capecitabine DRUG

AK129 is administered intravenously according to the frequency Q3W and different dosage of administration at different stages. Cadonilimab is administered intravenously according to the frequency and dosage 10mg/kg Q3W.Oxaliplatin is administered intravenously according to the frequency and dosage 130 mg/m2 on day 1 Q3W.Capecitabine is administered intravenously according to the frequency and dosage 1000 mg/m2 oral twice daily on day 1 to 14 Q3W.

The dose escalation and expansion stage of AK129 combined with chemotherapy with cadonilimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hanzhou, Zhejiang, 310005, China

Location

Study Officials

• Xiangdong Cheng, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao Xu, MD, PhD

CONTACT

+86 (0760) 8987 3999; clinicaltrials@akesobio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b/II, open-label, 2-part, multicenter, non-randomized, multiple-dose study

Study Record Dates

• First Submitted: September 4, 2024
• First Posted: September 19, 2024
• Study Start: September 10, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)