Clinical trial NCT05859750: A Study of AK104 With Chemotherapy as First-line Treatment in Patients With Advanced Pancreatic Cancer
Official title: A Multicenter, Open-label, Phase II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Combination With Chemotherapy as First-line Treatment in Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pancreatic Cancer
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2023-05-16
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 chemotherapy as first-line therapy in subjects with advanced unresectable or metastatic pancreatic ductal adenocarcinoma.


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.
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. Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors.
7. 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.
8. Pregnant or lactating women.
9. Patients who received any prior treatments targeting the mechanism of tumor immunity.
10. Patients with known contraindications to prescribed chemotherapy regimen (see instructions for specific drug).
11. Patients with known medical history of severe hypersensitivity reactions to other monoclonal antibodies or intravenous gamma globulin.
12. Active autoimmune disease within 2 years prior to the start of study treatmen.
13. Known active pulmonary tuberculosis.
14. Patients with active hepatitis B or active hepatitis C.
15. Known medical history of immunodeficiency or positive HIV test.
16. Patients with active infection.
17. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
18. Concurrent participation in another clinical study, unless it is an observational, non-interventional clinical study or the follow-up period of an interventional study.
19. 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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: The number of subjects experiencing adverse events (AEs)
timeFrame: From the subject signs the ICF to 90 days after the last dose of study treatment.
Secondary outcomes:
measure: Maximum observed concentration (Cmax) of AK104
timeFrame: From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.
measure: Minimum observed concentration (Cmin) of AK104 at steady state
timeFrame: From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.
measure: Area under the curve (AUC) of AK104
timeFrame: From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science And Technology
state: Hubei
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's hospital
state: Zhejiang
Study officials:
References: