Trial Title:
A Study of AK104 With Chemotherapy as First-line Treatment in Patients With Advanced Pancreatic Cancer
NCT ID:
NCT05859750
Condition:
Pancreatic Cancer
Conditions: Official terms:
Pancreatic Neoplasms
Paclitaxel
Gemcitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AK104
Description:
AK104 (6mg/kg) on day 1, IV, Q2W
Arm group label:
AK104 6mg/kg and chemotherapy
Intervention type:
Drug
Intervention name:
AK104
Description:
AK104 (10mg/kg) on day 1, IV, Q2W
Arm group label:
AK104 10mg/kg and chemotherapy
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Gemcitabine (1000mg/m2) on days 1, 8 and 15, IV, Q4W
Arm group label:
AK104 10mg/kg and chemotherapy
Arm group label:
AK104 6mg/kg and chemotherapy
Intervention type:
Drug
Intervention name:
Nab-Paclitaxel
Description:
Nab-Paclitaxel (125mg/m2) on days 1, 8 and 15, IV, Q4W
Arm group label:
AK104 10mg/kg and chemotherapy
Arm group label:
AK104 6mg/kg and chemotherapy
Summary:
This study is a multicenter, open-label, phase II study to evaluate the safety,
tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor
activities of AK104，a PD-1/CTLA-4 bispecific antibody, in combination with gemcitabine
and nab-paclitaxel as first-line therapy in subjects with advanced unresectable or
metastatic pancreatic ductal adenocarcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Ability to understand and voluntarily sign a written informed consent form (ICF),
which must be signed before the specified study procedures required for the study
are performed.
2. Males or females aged ≥ 18 years and ≤ 75 years at the time of signing the ICF.
3. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC).
4. Patients have not received prior systemic therapy for locally advanced or metastatic
pancreatic cancer; for patients who have received prior induction chemotherapy,
concurrent chemoradiotherapy, or adjuvant/neoadjuvant chemotherapy for curative
intent, the time between disease progression and last treatment should be at least 6
months.
5. Patients have at least one measurable tumor lesion per RECIST v1.1; lesions that
received radiotherapy are not selected as target lesions, unless the lesion is the
only measurable lesion and has unequivocal progression as judged by imaging, it can
be considered as a target lesion.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Expected survival ≥ 3 months.
8. Patients who have adequate organ function.
9. Women of childbearing potential must have a negative serum pregnancy test within 7
days prior to the first dose and agree to take effective contraception measures
during the study drug administration and within 120 days after the last dose. Male
patients with female partners of childbearing potential must agree to take effective
contraception measures during the study drug administration and within 120 days
after the last dose.
Exclusion Criteria:
1. Histologically or cytologically confirmed other pathological types, such as acinar
cell carcinoma, pancreatic neuroendocrine neoplasms or pancreatoblastoma.
2. Known active or untreated brain metastases, meningeal metastases, spinal cord
compression, or leptomeningeal disease. However, patients who meet the following
requirements and have measurable lesions outside the central nervous system are
allowed to be enrolled: asymptomatic after treatment and radiographically stable for
at least 4 weeks prior to the start of study treatment (e.g., no new or enlarged
brain metastases), and the systemic glucocorticoids and anticonvulsant medications
have been discontinued for at least 2 weeks.
3. Patients with known germ line BRAC1/2 mutation.
4. Presence of clinically symptomatic pleural effusion, pericardial effusion, or
ascites requiring frequent drainage (≥ 1/month).
5. Patients who, in the opinion of the investigator, have symptoms or signs suggestive
of clinically unacceptable deterioration of the primary disease at the time of
screening.
6. Medical history of gastrointestinal perforation or gastrointestinal fistula within 6
months prior to the first dose. If the perforation or fistula has been treated with
resection or repair and the disease has recovered or resolved as judged by the
Investigator, enrollment may be allowed.
7. Clinically significant gastrointestinal disorder including gastrointestinal
obstruction (including partial bowel obstruction), can not swallowing or
malabsorption syndrome, uncontrolled nausea, vomiting, diarrhea, or other
gastrointestinal disorders that severely affect nutrition absorption.
8. History of clinically significant hemorrhage symptom or clear hemorrhagic diathesis
within 1 month prior to the first dose, such as digestive tract hemorrhage, gastirc
ulcer hemorrhage or vasculitis.
9. Active malignancies within the past 3 years, with the exception of tumors in this
study and cured local tumors, such as basal cell carcinoma of skin, squamous cell
carcinoma of skin, superficial bladder cancer, carcinoma in situ of cervix,
carcinoma in situ of breast, localized prostate cancer, papillary thyroid
microcarcinoma, etc.
10. Major surgery other than the diagnosis of pancreatic cancer within 28 days prior to
the first dose or major surgery is expected during the study.
11. Presence of cardiovascular and cerebrovascular diseases or cardiovascular and
cerebrovascular risk factors.
12. Presence of ≥ Grade 2 peripheral neuropathy as defined by NCI CTCAE v5.0.
13. Presence of clinically active hemoptysis or active diverticulitis.
14. Patients with serious neurological or psychiatric disorders, including dementia and
epileptic seizure.
15. Pregnant or lactating women.
16. Patients who received any prior treatments targeting the mechanism of tumor
immunity, such as immune checkpoint blockades (e.g., anti-PD-1 antibody, anti-PD-L1
antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (e.g., antibodies
against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell therapy (e.g.,
CAR-T), etc.
17. Patients who received palliative local therapy for any tumor lesion within 2 weeks
prior to the first dose; systemic nonspecific immunomodulatory therapy (e.g.,
interleukin, interferon, thymosin, etc.) within 2 weeks prior to the first dose; and
Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor
indications within 2 weeks prior to the first dose.
18. Patients who require systemic treatment with glucocorticoids (> 10 mg/day prednisone
or equivalent) or other immunosuppressive drugs within 14 days prior to the first
dose.
19. Unresolved toxicities during prior anti-tumor therapy are defined as the toxicities
that do not resolved to National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Events (CTCAE) (NCI CTCAE v5.0) Grade 0 or 1, or to the levels specified
in the inclusion/exclusion criteria, with the exception of alopecia/pigmentation.
patients with irreversible toxicity that are not expected to worsen after study drug
administration (e.g., hearing loss) may be included in the study after consultation
with the medical monitor. patients with long-term toxicity due to radiotherapy that
cannot be recovered at the discretion of the Investigator may be included in the
study after consultation with the medical monitor.
20. Patients with known contraindications to NP and Gem chemotherapy (see instructions
for NP and Gem).
21. Patients with known medical history of severe hypersensitivity reactions to other
monoclonal antibodies or intravenous gamma globulin; patients with a known history
of allergy or hypersensitivity to AK104, nab-paclitaxel or other albumin products,
gemcitabine, or any component thereof.
22. Active autoimmune disease requiring systemic treatment within 2 years prior to the
start of study treatment, or autoimmune diseases that may relapse or require
scheduled treatment as judged by the Investigator, including, but not limited to,
inflammatory bowel disease, celiac disease, Wegener syndrome, Hashimoto's
thyroiditis, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune
hepatitis.
23. Known active pulmonary tuberculosis. patients with suspected active pulmonary
tuberculosis should be examined through chest imaging, sputum, and clinical symptoms
and signs.
24. Patients with active hepatitis B or active hepatitis C.
25. Known medical history of immunodeficiency or positive HIV test.
26. Known presence of interstitial lung disease or noninfectious pneumonitis that is
currently symptomatic or requires prior systemic glucocorticoid therapy that, in the
judgment of the Investigator, may affect the assessment or management of toxicity
related to study treatment.
27. Patients with active infection, including those requiring intravenous antibiotics or
antifungal therapy for 2 weeks prior to first dose, and unexplained fever during
screening (CTCAE≥1, except those determined by the investigator to be neoplasmic).
28. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation.
29. Patients must not have received a live vaccine within 28 days before the first dose,
and patients, if enrolled, should not receive live vaccines during the study or for
120 days after the last dose of AK104.
30. Concurrent participation in another clinical study, unless it is an observational,
non-interventional clinical study or the follow-up period of an interventional
study.
31. Any condition that, in the opinion of the Investigator, may result in a risk when
receiving the study drug, or would interfere with the evaluation of the study drug
or the safety of patients, or the interpretation of the study results.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking Union Medical College Hospital
Address:
City:
Beijing
Zip:
100005
Country:
China
Investigator:
Last name:
Wenming Wu, MD
Email:
Principal Investigator
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Investigator:
Last name:
Zhihua Li, MD
Email:
Principal Investigator
Facility:
Name:
Union Hospital Tongji Medical College Huazhong University of Science And Technology
Address:
City:
Wuhan
Country:
China
Investigator:
Last name:
Heshui Wu, MD
Email:
Principal Investigator
Facility:
Name:
Shandong Cancer Hospital
Address:
City:
Jinan
Zip:
250117
Country:
China
Investigator:
Last name:
He Tian, MD
Email:
Principal Investigator
Facility:
Name:
Shanghai Changhai Hospital
Address:
City:
Shanghai
Zip:
200433
Country:
China
Investigator:
Last name:
Gang Jin, MD
Email:
Principal Investigator
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Zip:
310005
Country:
China
Investigator:
Last name:
Qi Xu, MD
Email:
Principal Investigator
Facility:
Name:
Zhejiang Provincial People's hospital
Address:
City:
Hangzhou
Country:
China
Investigator:
Last name:
Yiping Mou, MD
Email:
Principal Investigator
Start date:
May 2023
Completion date:
June 2025
Lead sponsor:
Agency:
Akeso
Agency class:
Industry
Source:
Akeso
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05859750
