IBI343 plus gemcitabine and albumin‑bound paclitaxel for advanced pancreatic cancer

A Phase II Study to Evaluate the Safety, Tolerability, and Efficacy of IBI343 Combined With Chemotherapy in Advanced Pancreatic Cancer

This trial will test whether adding IBI343 to gemcitabine and albumin‑bound paclitaxel helps people with CLDN18.2‑positive advanced pancreatic adenocarcinoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang University (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Hangzhou, Zhejiang and 1 other locations)
• Trial ID: NCT06770439 on ClinicalTrials.gov

What this trial studies

This is a Phase II study with a safety lead‑in (Part 1) and a randomized extension (Part 2) testing IBI343 combined with standard gemcitabine plus albumin‑bound paclitaxel (AG) chemotherapy. Part 1 enrolls patients with CLDN18.2‑positive locally advanced or metastatic pancreatic adenocarcinoma regardless of prior systemic therapy to establish a safe dose and regimen. In Part 2, about 40 CLDN18.2‑positive patients who have not received prior systemic therapy will be randomized 1:1 to receive IBI343 plus AG versus AG alone. Key outcomes include safety, tolerability, and signals of anti‑tumor activity compared with chemotherapy alone.

Who should consider this trial

Good fit: Adults with histologically confirmed unresectable locally advanced, recurrent, or metastatic pancreatic adenocarcinoma whose tumors express CLDN18.2 and who meet protocol safety requirements are the intended participants; Part 2 requires no prior systemic therapy while Part 1 allows prior treatment.

Not a fit: Patients whose tumors do not express CLDN18.2, those eligible for curative surgery or radiotherapy, or those with major medical comorbidities or poor performance status are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, adding IBI343 could increase treatment responses or extend disease control compared with standard chemotherapy for patients with CLDN18.2‑positive advanced pancreatic cancer.

How similar studies have performed: Other CLDN18.2‑targeted therapies have shown promising results in gastric cancers and early signals in pancreatic cancer, but combining a CLDN18.2 agent with AG chemotherapy in this setting remains relatively novel.

Eligibility criteria

Inclusion Criteria:

* Signed written informed consent, willing and able to comply with the protocol specified visits and related procedures.
* Histopathologically confirmed unresectable locally advanced, recurrent, or metastatic pancreatic adenocarcinoma.
* Subjects must not be eligible for radical treatment such as radical radiotherapy and / or surgery; time to disease recurrence / metastasis\> 6 months for subjects with previous (new) adjuvant / adjuvant / radiotherapy) chemotherapy / radical chemoradiotherapy. In part 1: locally advanced or recurrent / metastatic stage with or without systemic therapy (including chemotherapy, targeted therapy, tumor immunotherapy, etc.). In part 2: The locally advanced or recurrent / metastasis phase has not received any systemic therapy (including chemotherapy, targeted therapy, tumor immunotherapy, etc.).
* At least 1 measurable lesion (no previous radiotherapy) for solid tumors RECIST v1.1.(At baseline, computed tomography or magnetic resonance imaging showed the long diameter of 10 mm (except for lymph nodes, the short axis of the lymph node must be 15 mm), the diameter of the target lesion is 2 times the imaging layer thickness and the lesion is suitable for repeated accurate measurement. If a lesion located in the previously irradiated area clearly demonstrates a progression meeting the RECIST V1.1 criteria, the lesion acts as a measurable lesion).
* Age was 18 years, and gender was unlimited.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0 or 1.
* The expected survival period was estimated at 12 weeks.
* Sufficient bone marrow and organ function.
* Female subjects of childbearing age or male partners of childbearing age should take effective contraception throughout the treatment period and within 6 months after the treatment period.
* Pathological tissue testing was confirmed as CLDN18.2 positive.

Exclusion Criteria:

* Is participating in another interventional clinical study, except for an observational (non-interventional) clinical study or is in the survival follow-up phase of the interventional study.
* Treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor within 2 weeks or 5 half-lives (whichever is longer) before the first dose of the study drug.
* The last anti-tumor therapy within 4 weeks before the first dose of the study drug or within 5 half-lives of the anti-tumor treatment (whichever is shorter) (2 weeks for washout with no exact half-life).
* Received therapeutic or palliative radiotherapy within 2 weeks prior to the first administration of the study drug.
* Receiving biliary stenting or PTCD within 7 days prior to the first use of study drug.
* Other anti-tumor treatment is planned during the study medication \[allows palliative radiotherapy for the purpose of relieving symptoms (e. g. pain) and does not affect efficacy evaluation\].
* Any live vaccine is administered within 4 weeks before the first dose of the study drug or during the duration of the study.
* A major surgical procedure (craniotomy, otomy, or tomy or otherwise defined by the investigator, excluding needle biopsy within 4 weeks before the first dose of study drug) or the presence of an unhealed wound, ulcer, or fracture; or a requirement that major surgery is planned during the study. For the purpose of palliative care, the local surgical treatment of isolated lesions is acceptable.

Any live vaccine within 4 weeks before the first dose of the study drug or during the duration of the study.

* A major surgical procedure (craniotomy, otomy, or tomy or otherwise defined by the investigator, excluding needle biopsy within 4 weeks before the first dose of study drug) or the presence of an unhealed wound, ulcer, or fracture; or a planned major surgery required during the study. For the purpose of palliative care, the local surgical treatment of isolated lesions is acceptable.
* Failure to recover to grade 0 or 1 prior to the first dose of study drug of NCI CTCAE v5.0 (excluding alopecia, fatigue, pigmentation, and other conditions with no safety risk as judged by the investigator).
* A history of gastrointestinal perforation and / or fistula within 6 months prior to the first dose of study drug was not resolved by surgery. presence of pyloric obstruction and / or persistent recurrent vomiting (3 times within 24 hours).
* After gastrointestinal or tracheal lumen stenting.
* Symptomatic CNS metastasis. For subjects with asymptomatic brain metastases (i. e., no glucocorticoid treatment, 1.5 cm treatment) or stable brain metastases after treatment, all the following criteria were required to participate in this study: no meson, pons, cerebellum, meninges, medullary or spinal cord metastasis; remained clinically stable for at least 4 weeks, confirmed clinical evidence of no new or expanded brain metastases, and stopped corticosteroid and anticonvulsant therapy for at least 2 weeks before the first dose of study drug. Note: The CNS is not used as a target lesion.
* Bone metastases at risk of paraplegia.
* Interstitial lung disease requiring steroid hormone therapy, or a history of - interstitial lung disease, non-infectious pneumonia, severely impaired or uncontrolled lung function, such as pulmonary fibrosis, severe radiation pneumonitis, acute lung injury, or is suspected during screening.
* There are diseases that fail to control History of the other primary malignancies.
* A known medical history of immunodeficiency.
* History of allogeneic organ transplantation and allogeneic HSCT.
* Previous treatment with antibody drug conjugates based on topoisomerase inhibitors.
* For medicated subjects, there was a previous history of allergy to the appropriate drug or preparation.
* For subjects receiving medication, there are contraindications to the drug.
* There was a history of prior drug-related non-morbidity.
* Female subjects in pregnancy or lactation.
* Other investigators are not eligible for participation in this study.

Where this trial is running

Hangzhou, Zhejiang and 1 other locations

• First Affiliated Hospital of Zhejiang University Schlool of Medicine — Hangzhou, Zhejiang, China (NOT_YET_RECRUITING)
• the First Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Tingbo Liang, MD.

Conditions: Advanced Pancreatic Cancers