Clinical trial NCT05636267: Study of AK119 and AK112 With or Without Chemotherapy for NSCLC Patients
Official title: A Multicenter, Open-Label, Phase Ib/II Study of AK119 and AK112 With or Without Chemotherapy in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: NSCLC
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2022-12-05
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase Ib/II study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of AK119 and AK112 With or Without Chemotherapy for NSCLC patients.


Eligibility criteria: Inclusion Criteria:

1. Be able to understand and voluntarily sign the written informed consent, which must be signed before the designated research procedure.
2. Age ≥ 18 and ≤ 75, male or female.
3. Local advanced or metastatic non-squamous NSCLC confirmed by histology or cytology according to eighth edition of the TNM classification for lung cancer.
4. EGFR activating mutation confirmed by tumor histology, cytology or hematology.
5. Failed to previous EGFR-TKI treatment.
6. ECOG performance status 0 to1.
7. Life expectancy ≥3 months.
8. At least one measurable lesion according to RECIST v1.1.
9. Adequate organ function.

Exclusion Criteria:

1. Histological or cytological pathology confirmed the presence of small cell carcinoma or squamous cell carcinoma.
2. Have suffered from the second primary active malignant tumor in the past 3 years.
3. There are other driving gene mutations that can obtain effective treatment.
4. Receipt of the following treatments or procedures: immunotherapy, including immunocheckpoint inhibitors, immunocheckpoint agonists, immunocellular therapy, and any other treatment targeting tumor immune mechanism; systematic chemotherapy in the advanced stage (IIIB-IV); anti-angiogenesis drugs, except for small molecule anti-angiogenesis drugs with drug withdrawal more than 4 weeks; extensive radiotherapy within 4 weeks; EGFR-TKIs within 2 weeks.
5. Symptomatic central nervous system metastases.
6. The toxicity of previous anti-tumor therapy has not been alleviated.
7. Uncontrolled massive ascites, pleural effusion or pericardial effusion.
8. Active autoimmune diseases in the past 2 years.
9. History of interstitial lung disease or noninfectious pneumonitis.
10. Suffering from clinically significant cardiovascular or cerebrovascular diseases.
11. History of severe bleeding tendency or coagulation dysfunction.
12. History of deep vein thrombosis, pulmonary embolism or any other serious thromboembolism in the past 3 months.
13. Serious infection in the past 4 weeks.
14. Acute exacerbation of chronic obstructive pulmonary disease or asthma in the past 4 weeks.
15. History of human immunodeficiency virus (HIV) infection.
16. History of severe hypersensitivity reactions to other mAbs.
17. History of organ transplantation.
18. Any other conditions that, in the opinion of the investigator, may increase the risk when receiving the investigational product.

Primary outcomes:
measure: Number of subjects with dose limiting toxicities (DLTs)
timeFrame: During the first 3 weeks
measure: Number of subjects with adverse events (AEs)
timeFrame: From the time of informed consent signed through 90 days after the last dose of study drug
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of response (DoR)
timeFrame: Up to 2 years
measure: Time to response (TTR)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Maximum observed concentration (Cmax) of AK119 and AK112
timeFrame: From first dose of study drug through last dose
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of study drug through last dose
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Yilong Wu, PhD
role: PRINCIPAL_INVESTIGATOR
References: