AK112 and Cadonilimab Combined With Chemotherapy for 1L Treatment of Metastatic Pancreatic Cancer

A Phase Ib/II Clinical Study of AK112 and Cadonilimab Combined With Chemotherapy as First-line Treatment for Metastatic Pancreatic Cancer

This trial is a Phase Ib/II study. All patients are stage IV pancreatic cancer (PDAC) patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The purpose of this study is to evaluate the safety and efficacy of AK112 and Cadonilimab combined with chemotherapy as first-line treatment for patients with metastatic pancreatic cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: AK112, Cadonilimab, nab-paclitaxel, gemcitabine; Drug: AK112, nab-paclitaxel, gemcitabine; Drug: nab-paclitaxel, gemcitabine

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
2. ≥18 years old and ≤ 75 years (regardless of sex).
3. ECOG performance status 0-1
4. Life expectancy longer than 3 months.
5. Histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal carcinoma (PDAC).
6. No prior systemic anti-tumor therapy for metastatic PDAC.
7. Adequate organ function.
8. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Exclusion Criteria:

1. Histological or cytological diagnosis of other pathological types.
2. BRCA1/2 or PALB2 mutations.
3. Participating in another clinical research.
4. Active central nervous system (CNS) metastases.
5. Undergoing systemic antiangiogenic therapy.
6. Acute or subacute pancreatitis.
7. Other known malignancies within five years.
8. Active infection requiring systemic therapy.

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadonilimab(q4w) + AK112 + nab-paclitaxel + gemcitabine(phase Ib); Cadonilimab will be administered at a selected dose every 4 weeks (q4w). AK112 will be administed at a fixed dose every 2 weeks (q2w). Nab-paclitaxel and gemcitabine will be administed at 125mg/m2 d1, d8, d15 q4w, and 1000mg/m2 d1, d8, d15 q4w, intravenously respectively.	Drug: AK112, Cadonilimab, nab-paclitaxel, gemcitabine; IV infusion, specified dose on specified days.
Experimental: Cadonilimab(q2w) + AK112 + nab-paclitaxel + gemcitabine(phase Ib); Cadonilimab will be administered at a selected dose every 2 weeks (q2w). AK112 will be administed at a fixed dose every 2 weeks (q2w). Nab-paclitaxel and gemcitabine will be administed at 125mg/m2 d1, d8, d15 q4w, and 1000mg/m2 d1, d8, d15 q4w, intravenously respectively.	Drug: AK112, Cadonilimab, nab-paclitaxel, gemcitabine; IV infusion, specified dose on specified days.
Experimental: Cadonilimab + AK112 + nab-paclitaxel + gemcitabine(phase II); Cadonilimab will be administered at a selected dose and frequency from phase Ib. AK112 will be administered at a fixed dose every 2 weeks (q2w). Nab-paclitaxel and gemcitabine will be administed at 125mg/m2 d1, d8, d15 q4w, and 1000mg/m2 d1, d8, d15 q4w, intravenously respectively.	Drug: AK112, Cadonilimab, nab-paclitaxel, gemcitabine; IV infusion, specified dose on specified days.
Experimental: AK112 + nab-paclitaxel + gemcitabine(phase II); AK112 will be administered at a fixed dose every 2 weeks (q2w). Nab-paclitaxel and gemcitabine will be administed at 125mg/m2 d1, d8, d15 q4w, and 1000mg/m2 d1, d8, d15 q4w, intravenously respectively.	Drug: AK112, nab-paclitaxel, gemcitabine; IV infusion, specified dose on specified days.
Active Comparator: nab-paclitaxel + gemcitabine(phase II); Nab-paclitaxel and gemcitabine will be administed at 125mg/m2 d1, d8, d15 q4w, and 1000mg/m2 d1, d8, d15 q4w, intravenously respectively.	Drug: nab-paclitaxel, gemcitabine; IV infusion, specified dose on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events (AEs) and serious adverse events (SAEs)	Frequency of AEs and SAEs for all Arms in phase Ib.	28days+28days
Overall Response Rate (ORR)	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK)	PK parameters: serum concentrations of AK112 and Cadonilimab at different point of time	Up to Cycle 12
Anti-Drug Antibodies(ADAs)	Number and percentage of patients with detectable anti-drug antibodies	Up to approximately 2 years
Progression-Free Survival (PFS)	Evaluation of PFS based on RECIST v1.1.	Up to approximately 2 years
Overall survival (OS)	Evaluation of OS based on RECIST v1.1.	Up to approximately 2 years
Disease control rate (DCR)	Evaluation of DCR based on RECIST v1.1.	Up to approximately 2 years
Duration of Response (DoR)	Evaluation of DoR based on RECIST v1.1.	Up to approximately 2 years
Time to Response (TTR)	Evaluation of TTR based on RECIST v1.1.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: AK112-210

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No