A Study of AK104 in Combination With Chiauranib in Patients With Extensive Stage Small Cell Lung Cancer

A Phase Ib/II Clinical Study of Anti-PD-1 and CTLA-4 Bispecific Antibody, Cadonilimab(AK104), in Combination With Chiauranib in the Treatment of Patients With Extensive Stage Small Cell Lung Cancer Who Failed First-line Platinum-based Chemotherapy in Combination With Programmed Cell Death-1(PD1)/Programmed Cell Death Protein Ligand-1(PDL1) Inhibitors

A Phase Ib/II open label,international multicentre study to evaluate the efficacy and safety of anti-PD-1 and CTLA-4 bispecific antibody AK104 in combination with Chiauranib in Patients with Extensive Stage Small Cell Lung Cancer Who Failed First-line Platinum-based Chemotherapy in Combination with PD1/PDL1 Inhibitors

Study Overview

• Status: Recruiting
• Conditions: SCLC,Extensive Stage
• Intervention / Treatment: Drug: AK104 IV infusion；Chiauranib oral

Detailed Description

Small cell lung cancer (SCLC) consists 15% of the lung cancer.Because of the high malignancy, poor cell differentiation, and rapid proliferation of SCLC, 65% of the patients were in the extensive stage at their first presentation in the hospital with a very poor prognosis. There were few options of second-line therapies for patients who experienced progress disease during or after the end of first-line platinum-based regimens. Several studies showed that PD-1/PD-L1 inhibitors had synergistic anti-tumor effects with anti-vascular endothelial growth factor(VEGF) agents, i.e., PD-1/PD-L1 inhibitors could restore the anti-tumor effect of the immune system by blocking PD-L1, and anti-VEGF agents could improve the efficacy of the former by blocking the immunosuppressive effect of VEGF and promoting the infiltration of T cells in tumor tissues. Immunotherapy in combination with antiangiogenic therapy may become a trend in the treatment of extensive stage small cell lung cancer(ES-SCLC). The aim of this international multicentre phase Ib/II trial is to evaluate the efficacy-objective response rate according to RECIST criteria and safety-incidence and severity of adverse events.The patients' recruitment timeframe is set at 16 months and approximately 42 patients will be included.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia
      • Recruiting
      • Westmead Hospital
      • Principal Investigator: Adnan Nagrial
  • Queensland
    • South Brisbane, Queensland, Australia
      • Recruiting
      • Icon Cancer Centre
      • Principal Investigator: Jim Coward
    • Woolloongabba, Queensland, Australia
      • Recruiting
      • Princess Alexandra Hospital
      • Principal Investigator: Kenneth O'Byrne
  • South Australia
    • Bedford Park, South Australia, Australia
      • Recruiting
      • Flinders Medical Centre
      • Principal Investigator: Nazim Abbas
  • Victoria
    • Frankston, Victoria, Australia
      • Recruiting
      • Peninsula & South Eastern Haematology and Oncology Group
      • Principal Investigator: Vinod Ganju
    • St Albans, Victoria, Australia
      • Recruiting
      • Sunshine Hospital
      • Principal Investigator: Suzanne Kosmider
• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • Recruiting
      • Jilin Province Cancer Hospital
      • Contact: Ying Cheng, Professor; Phone Number: 0431-80596315; Email: jl.cheng@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject must sign the written informed consent form (ICF) voluntarily.
2. Aged ≥ 18 to ≤ 75 years.
3. Eastern Cooperative Oncology Group(ECOG) performance status score of 0 or 1.
4. Life expectancy≥ 3 months.
5. Histologically or cytologically confirmed ES-SCLC according to the Veterans Administration Lung Study Group(VALG) stage.
6. Phase Ib and II: Subjects with ES-SCLC who have failed prior first-line platinum-based chemotherapy in combination with PD1/PDL1 inhibitors will be enrolled.
7. At least 1 measurable lesion per RECIST v1.1, which is applicable for repeated accurate measurement. Brain metastatic lesions are not considered target lesions.
8. Adequate organ function.
9. Women of childbearing potential must have a negative urine or serum pregnancy test
10. If a nonsterile male subject has sexual intercourse with a female partner of childbearing potential, he must use an effective method of contraception from the start of screening until Day 120 after the last dose; it should be discussed with the Investigator whether contraception should be discontinued after this time point.
11. Subjects must be willing and able to comply with the scheduled visits, treatment regimens, laboratory tests, and other requirements in the study.

Exclusion Criteria:

1. Malignancies other than SCLC within 3 years prior to enrollment. However, subjects with other malignancies that have been cured are eligible.
2. Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study.
3. Subjects whose imaging at screening shows that the tumor encircles important blood vessels or has significant necrosis and cavitation, and the subjects'participation is associated with a risk of hemorrhage.
4. Tumor invasion of surrounding vital organs and blood vessels.
5. Subjects who had active autoimmune disease that required systemic treatment in the past two years.
6. Subjects with prior history of non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy or with non-infectious pneumonitis at present.
7. Presence of metastases to brainstem, meninges and spinal cord, or spinal cord compression.
8. Subjects with pleural effusion, pericardial effusion, or ascites that are clinically symptomatic or require drainage.
9. Subjects with unresolved toxicity due to prior anti-tumor therapy, defined as failure to recover to National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) v5.0 Grade 0 or 1 (except for alopecia) or to the levels specified in the inclusion/exclusion criteria.
10. Subjects who cannot swallow pills, and who have malabsorption syndrome, or any condition affecting gastrointestinal absorption. Subjects with active or prior history of definite inflammatory bowel disease.
11. Subjects with a history of immunodeficiency; a positive human immunodeficiency virus (HIV) antibody test; and current long-term use of systemic corticosteroids or other immunosuppressants.
12. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
13. Subjects who had major surgical procedure or serious trauma within 30 days prior to the first dose, or a major scheduled surgery within 30 days after the first dose; subjects who had minor local surgery within 3 days prior to the first dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104 once every 3 weeks and Chiauranib once a day; Subjects receive AK104 once every 3 weeks plus Chiauranib once a day until intolerable toxicity, no more clinical benefit as judged by the investigator, or completion of 24 months of treatment, or meeting other criteria for termination of treatment in the protocol, whichever occurs first.	Drug: AK104 IV infusion；Chiauranib oral; AK104 IV infusion once every 3 weeks；Chiauranib once a day oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is proportion of subjects with complete response(CR) or partial response(PR), based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1	Up to approximately 2 years
Incidence and severity of adverse events(AEs)	Incidence and severity of AEs is aim to evaluate the safety of AK104 in combination with Chiauranib.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Disease control rate (DCR) is defined as the proportion of subjects achieving a best of response(BOR) of confirmed CR and PR and stable disease(SD) per RECIST v1.1.	Up to approximately 2 years
duration of response (DoR)	Duration of response (DoR) is defined as the period from the first documentation of confirmed response (CR or PR) to the first documentation of progressive disease(PD) (as per RECIST v1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years
time to response (TTR)	Time to response (TTR) is defined as the time from the first dose of investigational products until the first confirmation of CR or PR.	Up to approximately 2 years
progression-free survival (PFS)	Progression-free survival (PFS) is defined as the time from the first dose of investigational products until documentation of PD (as per RECIST v1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years
overall survival (OS)	Overall survival (OS) is defined as the time from the first dose of investigational products until death due to any cause.	Up to approximately 2 years
Pharmacokinetics(PK) profiles	Serum concentrations of AK104 and plasma concentrations of Chiauranib in individual subjects at different time points after administration of AK104 in combination with Chiauranib.	Up to approximately 2 years
Immunogenicity assessment	The immunogenic potential of AK104 in combination with Chiauranib will be assessed by summarizing the number and percentage of subjects with detectable antidrug antibody(ADA).	Up to approximately 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
alpha thalassemia/mental retardation X-linked(ATRX) gene mutation status	The ATRX gene mutation status in peripheral blood will be determined, and its correlation with efficacy indicators such as ORR, PFS and OS will be analyzed.	Up to approximately 2 years
SCLC subtype	The expression of proteins related to SCLC subtype in tumor tissue samples will be detected by immunohistochemistry (IHC) and its correlation with efficacy will be analyzed.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Collaborators: Chipscreen Biosciences, Ltd.
• Investigators: Principal Investigator: Ying Cheng, Professor, Jilin Province Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 16, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Chiauranib
• Other Study ID Numbers: AK104-212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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