A Phase Ib/II Study of ATG-022 Plus Pembrolizumab With/Without Chemotherapy in Participants With Claudin (CLDN) 18.2-positive, HER2-negative, Unresectable or Metastatic Gastric or Gastroesophageal Junction AdenocarcinomaUnresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Official title

A Phase Ib/II Study of ATG-022 Plus Pembrolizumab With/Without Chemotherapy in Participants With Claudin (CLDN) 18.2-positive, HER2-negative, Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Overview

This is A Phase Ib/II Study of ATG-022 Plus Pembrolizumab With/Without Chemotherapy in Participants With Claudin (CLDN) 18.2-positive, HER2-negative, Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Detailed description

This is a phase Ib/II Study of ATG-022 plus pembrolizumab with/without chemotherapy in participants with CLDN 18.2-positive, HER2-negative, PD-L1 positive (CPS≥1), unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Both the intervention of ATG022 + Pembrolizumab (A+P) and the intervention of ATG-022 + pembrolizumab + chemotherapy (CAPOX regimen, A+P+C) consist of a Ib and II phase.

Participants with CLDN 18.2-positive, HER2-negative, PD-L1 positive (CPS≥1) advanced or metastatic gastric or gastroesophageal junction adenocarcinoma and having progressed on or after at least one prior systemic therapy, will be enrolled in the intervention of A + P.

Participants with CLDN 18.2-positive, HER2-negative, PD-L1 positive (CPS≥1) advanced or metastatic gastric or gastroesophageal junction adenocarcinoma and having not received any prior systemic therapy, will be enrolled in the intervention of A + P + C. The study will be firstly initiated from Ib of the intervention of A+P. The initiation of the intervention of A+P+C will be based on the clinical data of A+P

Interventions

• Drug ATG-022
  1.8mg/kg Q3W, every 21 days as one cycle
• Drug pembrolizumab/KEYTRUDA®
  20mg Q3W, every 21 days as one cycle
• Drug CAPOX
  Standard Dose level for CAPOX: Capecitabine 1000 mg/m2 PO BID on Day 1-14, Oxaliplatin 130 mg/m2 IV on Day 1, Cycled every 21 days (3 weeks) for 8 cycles.

Primary outcome measures

• AEs and SAEs [Time frame: 12 months after the last subject enrolled]
• DLT [Time frame: Up to 21 Days]
• RP2D [Time frame: Up to 21 Days]

Secondary outcome measures (4)

• ORR [Time frame: 12 months after the last subject enrolled]
• DOR [Time frame: 12 months after the last subject enrolled]
• PFS [Time frame: 12 months after the last subject enrolled]
• Plasma concentration of ATG-022 and derived PK paramete [Time frame: One year after last patient first dose]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling, and analyses.
• Aged ≥18 years as of the date of consent.
• Histological or cytological confirmation of gastric cancer or gastroesophageal junction adenocarcinoma with CLDN 18.2 positive, HER2-negative and PD-L1 positive expression.
• Archival tumor tissue sample within 36 months prior to participating in the study or newly obtained biopsy of a tumor lesion not previously irradiated should be provided for testing of CLDN 18.2 and PD-L1 expression for determining the criteria.
• At least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 by investigators.
• Estimated life expectancy of a minimum of 12 weeks.

Exclusion criteria

• Known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention.
• Prior exposure to CLDN 18.2 ADC, CLDN 18.2 chimeric antigen receptor T-cell immunotherapy or agents containing MMAE.
• Prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study treatment or within a period during which the investigational product or systemic anticancer treatment has not been cleared from the body (e.g., a period of 5 'halflives'), whichever is the most appropriate as judged by the investigator.
• Received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
• Prior radiotherapy within 4 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids. Two weeks or fewer of palliative radiotherapy for non- central nervous system disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention
• Prior a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Prior major surgery (excluding placement of vascular access) within 28 days of the first dose of study treatment or minor surgical procedures≤7 days. No waiting is required following implantable port and catheter placement.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 30 centers

• Anhui Provincial Hospital — Hefei
• The First Affiliated Hospital of Anhui Medical University — Hefei
• Beijing Cancer hospital — Beijing
• Fujian Provincial Cnacer Hospital — Fuzhou
• The First Affiliated Hospital of Xiamen University — Xiamen
• Gansu Provincial Cnacer Hospital — Lanzhou
• Cancer Institute&Hospital Chinese Academy of Medical Sciences — Langfang
• The Fourth Hospital of Hebei Medical University — Shijiazhuang
• … and 22 more centers

Identifiers

NCT: NCT07327229 · ATG-022-GC-001 · KEYNOTE-G37 · MK-3475-G37

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗