A Study of AK104 With Chemotherapy as First-line Treatment in Patients With Advanced Pancreatic Cancer

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: AK104; Drug: AK104; Drug: Gemcitabine; Drug: Nab-Paclitaxel; Drug: Oxaliplatin + Irinotecan + 5-Fluorouracil/Leucovorin; Drug: Liposomal Irinotecan, Oxaliplatin, 5-Fluorouracil/Calcium folinate

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhifang Yao, MD; Phone Number: +86-0760-89873999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Recruiting
      • Peking Union Medical College Hospital
      • Principal Investigator: Wenming Wu, MD
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Principal Investigator: Zhihua Li, MD
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
      • Principal Investigator: Heshui Wu, MD
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Shandong Cancer Hospital
      • Principal Investigator: He Tian, MD
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Changhai Hospital
      • Principal Investigator: Gang Jin, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Recruiting
      • Zhejiang Cancer Hospital
      • Principal Investigator: Qi Xu, MD
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Principal Investigator: Yiping Mou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104 6mg/kg and AG	Drug: AK104; AK104 (6mg/kg) on day 1, IV, Q2W; Drug: AK104; AK104 (10mg/kg) on day 1, IV, Q2W; Drug: Gemcitabine; Gemcitabine (1000mg/m2) on days 1, 8 and 15, IV, Q4W; Drug: Nab-Paclitaxel; Nab-Paclitaxel (125mg/m2) on days 1, 8 and 15, IV, Q4W
Experimental: AK104 10mg/kg and AG	Drug: AK104; AK104 (6mg/kg) on day 1, IV, Q2W; Drug: AK104; AK104 (10mg/kg) on day 1, IV, Q2W; Drug: Gemcitabine; Gemcitabine (1000mg/m2) on days 1, 8 and 15, IV, Q4W; Drug: Nab-Paclitaxel; Nab-Paclitaxel (125mg/m2) on days 1, 8 and 15, IV, Q4W
Experimental: AK104 and mFOLFIRINOX	Drug: AK104; AK104 (6mg/kg) on day 1, IV, Q2W; Drug: AK104; AK104 (10mg/kg) on day 1, IV, Q2W; Drug: Oxaliplatin + Irinotecan + 5-Fluorouracil/Leucovorin; oxaliplatin, 85 mg/m²; irinotecan, 180 mg/m²; leucovorin, 400 mg/m²; and fluorouracil, 400 mg/m² given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks
Experimental: AK104 and NALIRIFOX	Drug: AK104; AK104 (6mg/kg) on day 1, IV, Q2W; Drug: AK104; AK104 (10mg/kg) on day 1, IV, Q2W; Drug: Liposomal Irinotecan, Oxaliplatin, 5-Fluorouracil/Calcium folinate; liposomal irinotecan 50 mg/m², oxaliplatin 60 mg/m², leucovorin 400 mg/m², and fluorouracil 2400 mg/m², administered sequentially as a continuous intravenous infusion over 46 h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is the proportion of subjects with CR or PR based on RECIST v1.1	Up to 2 years
The number of subjects experiencing adverse events (AEs)	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.	From the subject signs the ICF to 90 days after the last dose of study treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration (Cmax) of AK104	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.	From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.
Minimum observed concentration (Cmin) of AK104 at steady state	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.	From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.
Area under the curve (AUC) of AK104	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.	From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.
Number of subjects who develop detectable anti-drug antibodies (ADAs)	The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).	From first dose of study drug until the 8th cycle (each cycle is 28 days) of study drug administration.

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 14, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Calcium-Regulating Hormones and Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Oxaliplatin; Irinotecan; Gemcitabine; Calcium; Fluorouracil; Leucovorin; Levoleucovorin; Paclitaxel
• Other Study ID Numbers: AK104-217

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No