AK112 and AK104 With or Without Chemotherapy in Advanced Non-small Cell Lung Cancer

Advanced Non-small-cell Lung Cancer Clinical Trial

Official title:

A Phase Ib/II Clinical Trial of AK112 and AK104 With or Without Chemotherapy in Advanced Non-small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05904379
• Other study ID #: AK112-208
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 13, 2023
• Est. completion date: January 31, 2027

Study information

• Verified date: March 2024
• Source: Akeso
• Contact: Jie Yang, MD
• Phone: +86(0760)89873999
• Email: clinicaltrials[@]akesobio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is a Phase Ib/II study. All patients are stage IIIB/C (unsuitable for radical therapy) or IV non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the safety and efficacy of AK112 and AK104 with or without chemotherapy in subjects with advanced NSCLC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 233
• Est. completion date: January 31, 2027
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of NSCLC.
• Has Stage IIIB/C or IV NSCLC (American Joint Committee on Cancer [AJCC 8th]).
• 18-75 years old (at the time consent is obtained).
• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
• Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue.
• Has a life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the site study team.
• Has no EGFR-sensitive mutations or ALK gene translocations.
• Has adequate organ function.
• Has recovered from the effects of any prior radiotherapy or surgery.
• All female and male subjects of reproductive potential must agree to use an effective method of contraception, during and for 120 days after the last dose of study treatment.

Exclusion Criteria:

• Has any histologically small cell carcinoma component.
• Is currently participating in a study of an investigational agent or using an investigational device.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment.
• Has undergone major surgery within 30 days of Study Day 1.
• Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Has an active infection requiring systemic therapy.
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Has a history of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
• Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.

Related Conditions & MeSH terms

• Advanced Non-small-cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• AK112
Subjects receive AK112 intravenously.
• AK104
Subjects receive AK104 intravenously.
• Carboplatin
Subjects receive carboplatin intravenously.
• paclitaxel
Subjects receive paclitaxel intravenously.
• pemetrexed
Subjects receive pemetrexed intravenously.
• Docetaxel
Subjects receive docetaxel intravenously.

Locations

Country	Name	City	State
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Shanghai Pulmonary Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Akeso

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety reflected by AE	Safety will be reflected by AE, which is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to 2 approximately years
Primary	ORR per RECIST v1.1	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1.	Up to 2 approximately years
Secondary	OS	Overall Survival (OS) is defined as the time from the start of treatment with AK112 until death due to any cause.	Up to 2 approximately years
Secondary	DoR per RECIST v1.1	Duration of response (DoR) assessed according to RECIST v1.1.	Up to 2 approximately years
Secondary	DCR per RECIST v1.1	Disease control rate (DCR) assessed according to RECIST v1.1.	Up to 2 approximately years
Secondary	TTR per RECIST v1.1	Time to response (TTR) is defined as the time to response base on RECIST v1.1.	Up to 2 approximately years
Secondary	PFS per RECIST v1.1	Progression-free survival (PFS) is defined as the time from the date of Initial administration till the first documentation of disease progression assessed by the investigator or death due to any cause (whichever occurs first).	Up to 2 approximately years
Secondary	AK112 serum concentration	The serum concentration of AK112 of individual subjects at different time points.	Up to 2 approximately years
Secondary	AK104 serum concentration	The serum concentration of AK104 of individual subjects at different time points.	Up to 2 approximately years
Secondary	ADA	Number of subjects with detectable anti-drug antibodies (ADA).	Up to 2 approximately years
Secondary	PD-L1 expression	The correlationship between PD-L1 expression and efficacy.	Up to 2 approximately years
Secondary	ctDNA	The correlationship between ctDNA detection and efficacy.	Up to 2 approximately years