A Phase 1a/1b, Multicenter, Open-label, First-in-human Study of GNX1021 in Subjects with Unresectable Locally Advanced or Metastatic Gastrointestinal Cancers
GNX1021-01
EPS Corporation jRCT Inquiry Center
EPS Corporation
2-23 Shimomiyabicho, Shinjuku-ku, Tokyo
+81-3-5684-7797
jRCT-inquiry@eps.co.jp
EPS Corporation jRCT inquiry reception center
EPS Corporation
2-23 Shimomiyabicho, Shinjuku-ku, Tokyo
+81-3-5684-7797
jRCT-inquiry@eps.co.jp
Recruiting
June. 08, 2026
July. 01, 2026
64
Interventional
single arm study
open(masking not used)
dose comparison control
single assignment
treatment purpose
Inclusion Criteria to be met for both Phase 1a and Phase 1b:
1) Subjects must be able to understand and voluntarily provide written informed consent and be willing and able to comply with all protocol-specified visits and study-related procedures.
2) Subjects must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimens collected within the past five years or agree to undergo a fresh biopsy.
3) Subjects must have at least one measurable lesion as defined by RECIST v1.1.
4) Subjects must be aged >= 18 years at the time of informed consent.
5) Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
6) Subjects must have an estimated life expectancy of at least 12 weeks.
7) Subjects must have adequate bone marrow and organ function.
8) Female subjects of childbearing potential must agree to use effective contraceptive measures throughout the treatment period and for at least 7 months after the last dose and male subjects whose partners are female of childbearing potential must agree to use effective contraceptive measures throughout the treatment period and for 4 months after the last dose.
Inclusion Criteria for Phase 1a:
1) Subjects must have pathologically confirmed unresectable, locally advanced, or metastatic gastrointestinal cancers that have current progressive diseases and no further standard therapy is available.
Inclusion Criteria for Phase 1b:
1) Subjects must have histo-pathologically confirmed unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinomas (Cohort A), and metastatic pancreatic ductal adenocarcinoma (Cohort B).
2) For G/GEJ AC, subjects must have:
- received at least 1 prior line of systemic therapy (anti-PD-(L)1 + platinum/ fluoropyrimidines);
- received anti-HER2 therapy for HER2 overexpression subjects;
3) For PDAC, subjects must have:
- received and disease progressed from prior gemcitabine-based systemic chemotherapy for metastatic disease.
4) Subjects must have bLeB/Y-positive tumors as confirmed by central pathological review.
Exclusion criteria to be met for both Phase 1a and Phase 1b:
1) Participation in another interventional study (except observational)
2) Prior antineoplastic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to first dose
3) Planned other anti-tumor therapy during the study (palliative radiotherapy for symptomatic relief that does not affect response assessment is allowed)
4) Strong CYP3A4 inhibitor use within 2 weeks or 5 half-lives (whichever is longer) prior to first dose
5) Live vaccine within 4 weeks prior to enrollment or planned during study
6) Toxicities from prior therapy not recovered to Grade 0/1 (except clinically insignificant)
7) Major surgery within 4 weeks, unhealed wounds, or planned major surgery during the study period
8) Prior whole pelvic radiotherapy
9) Grade >= 2 peripheral neuropathy or active/chronic corneal disorder
10) Gastric pyloric obstruction or persistent vomiting (>= 3 episodes/24 hr)
11) Unresolved GI perforation and/or fistula within 6 months
12) Active CNS metastases
13) Interstitial lung disease, pneumonitis, or uncontrolled/severe pulmonary disease, or suspected of having the above diseases
14) Uncontrolled or clinically significant medical conditions
15) Other active malignancies (Excluding previously treated patients under certain conditions)
16) Immunodeficiency or history of allogeneic transplantation
17) Pregnant, breastfeeding, or unable to exclude pregnancy
18age old over
No limit
Both
Gastrointestinal cancer
Drug: GNX1021
Dose Escalation/Dose Finding part (P1a): Planned doses are 0.15, 0.3, 0.6, 1, 1.5, 2, and 2.5 mg/kg. GNX1021 is injected intravenously (IV) on Day 1 of each cycle (21 days per cycle).
Cohort Expansion part (P1b): Intravenous infusion (IV) on Day 1 of each cycle (21 days per each cycle) at the dose determined in P1a.
1) AEs during the study: incidences of AEs, SAEs, infusion-related AEs, CTCAE grade >=3 AEs, and AEs related to study drug.
1) Safety laboratory parameters (hematology, biochemistry, and coagulation factors).
2) PK parameters (clearance, volume of distribution [Vd] and area-under-theconcentration-time curve [AUC0-last and AUC0-inf]), maximum concentration [Cmax], time of Cmax [Tmax], pre-dose values, and half-life of GNX1021 [ADC, total antibody, and unconjugated MMAE]).
3) Immunogenicity (anti-drug antibodies) of GNX1021.
4) Changes in CEA and CA 19-9 if either are elevated at baseline.
5) Anti-tumor activity measured by tumor shrinkage (based on computerized tomography [CT] scan evaluations).
6) Objective Response (Complete Response [CR] or Partial Response [PR]), Disease Control (CR, PR, or Stable Disease [SD]) after 6, 12, 24 and 36 weeks, Progression-Free Survival (PFS) and Duration of Response (DoR), as assessed
according to RECIST v1.1.
