A Phase II Clinical Study to Evaluate the Efficacy and Safety of HLX43 (Anti-PD-L1 ADC) in Subjects With Advanced Pancreatic Cancer
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Shanghai Henlius Biotech
- Enrollment
- 100
- Primary Endpoint
- ORR
Overview
Brief Summary
The study is being conducted to to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in Patients with Pancreatic ductal adenocarcinoma (PDAC)
Detailed Description
This study is an open-label phase II clinical study to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in Patients with Pancreatic ductal adenocarcinoma (PDAC). In this study, eligible subjects will be randomized at 1:1 ratio, and the patients will be administered with HLX43 at different doses via intravenous infusion.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Fully understand the study content, procedures, and potential adverse reactions before the trial, sign the informed consent form (ICF), voluntarily participate in the trial, and be able to complete the study per the protocol requirements;
- •Age ≥ 18 years, ≤75 years, at the time of signing the ICF, regardless of gender;
- •Histologically or cytologically confirmed, unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC),who has failed at least one prior line of standard systemic therapy. The prior therapy must have included a fluoropyrimidine-based or gemcitabine-based regimen;
- •At least one measurable lesion per RECIST v1.1 within 4 weeks before randomization;
- •Willing to provide archived (preferably within 2 years) or fresh tumor tissue specimens for the detection of PD-L1 expression.
- •At least 3 weeks (or 5 half-lives, whichever is shorter) since last major surgery, medical device treatment, radiotherapy (except palliative bone radiotherapy), cytotoxic chemotherapy, immunotherapy, or biological therapy; ≥2 weeks since last hormonal therapy or small molecule targeted therapy; ≥1 week since last traditional Chinese medicine treatment with anti-tumor indications or minor surgery; with treatment-related adverse events recovered to CTCAE v5.0 ≤ grade 1 (except grade 2 peripheral neuropathy and alopecia);
- •ECOG performance status 0-2 within 1 week before randomization;
- •Expected survival ≥ 3 months；
- •Adequate organ function within 1 week before randomization (no blood transfusion or colony-stimulating factors within 14 days prior to first dose)
- •Fertile participants must use ≥1 highly effective contraceptive method during the trial and for ≥6 months after last dose; females of childbearing potential must have negative pregnancy test within 7 days before enrollment.
Exclusion Criteria
- •Histologically or cytologically confirmed as other pathological types of pancreatic cancer or containing components of other pathological differentiation;
- •Prior treatment with an antibody-drug conjugate (ADC) of topoisomerase I;
- •Received radical radiotherapy within 3 months prior to the first dose;
- •History of other malignancies within 2 years prior to randomization (except radically treated early-stage malignancies);
- •History of an adverse event that led to permanent discontinuation of prior immunotherapy, or a history of ≥ Grade 2 immune-mediated pneumonitis or immune-mediated myocarditis;
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Presence of spinal cord compression or clinically active central nervous system metastases (defined as untreated or symptomatic metastases, or those requiring corticosteroids or anticonvulsants), carcinomatous meningitis, or leptomeningeal disease;
- •History or presence of clinically significant pulmonary impairment due to concurrent lung disease, Subjects with a history of radiation pneumonitis within the past 6 months are also excluded;
- •Poorly controlled cardiovascular/cerebrovascular conditions;
- •Active systemic infections requiring IV antibiotics within 2 weeks pre-randomization;
Arms & Interventions
HLX43 DOSE 1 (2.5 mg/kg)
Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)
Intervention: HLX43 DOSE 1 (2.5 mg/kg) (Drug)
HLX43 DOSE 2 (3.0 mg/kg)
Patients with good tolerability and well controlled disease will receive the treatment once every 3 weeks (Q3W), Until disease progression, initiation of a new anti-tumor therapy, death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurs first)
Intervention: HLX43 DOSE 2 (3.0 mg/kg) (Drug)
Outcomes
Primary Outcomes
ORR
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks
Objective response rate (ORR) is the proportion of subjects with the best overall response being CR or PR (assessed by investigator per RECIST v1.1)
PFS
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Defined as the time (in months) from randomization to the first confirmed and documented progressive disease or death (whichever occurs first) as assessed by INV per RECIST v1.1.
Secondary Outcomes
- ORR(up to 24 week)
- PFS(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months)
- OS(From randomization to death from any cause (up to approximately 18 months))
- DOR(up to 18 months)
- DCR(up to 12 months)
- Incidence and severity of adverse events (AEs)(time from the date of the first dose of study drug until 90 days after last dose, assessed up to 18 months)