Study of AK119 and AK112 With or Without Chemotherapy for NSCLC Patients

Phase 1

Recruiting

• Conditions: NSCLC
• Interventions: Drug: AK119; Drug: AK112; Drug: Pemetrexed; Drug: Carboplatin

• Registration Number: NCT05636267
• Lead Sponsor: Akeso

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-09
• Study First Submitted QC: 2022-11-23
• Study First Posted: 2022-12-05
• Study Start: 2023-02-10
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-07
• Last Update Posted: 2023-03-09
• Primary Completion: 2024-12
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 114

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AK119 + AK112 + Pemetrexed + Carboplatin	AK119	Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
AK119 + AK112 + Pemetrexed + Carboplatin	AK112	Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
AK112	AK112	Subjects will receive AK112 monotherapy via intravenously (IV) Q3W, up to 2 years.
AK119 + AK112	AK112	Subjects will receive AK119 plus AK112 via intravenously (IV) Q3W, up to 2 years.
AK119 + AK112 + Pemetrexed + Carboplatin	Carboplatin	Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
AK119 + AK112 + Pemetrexed + Carboplatin	Pemetrexed	Subjects will receive AK119 and AK112 plus pemetrexed and carboplatin via intravenously (IV) Q3W, up to 4 cycles. Afterward, AK119 and AK112 plus pemetrexed will continue to be treated up to 2 years.
AK119 + AK112	AK119	Subjects will receive AK119 plus AK112 via intravenously (IV) Q3W, up to 2 years.

Primary Outcome Measures

Name	Time	Method
Number of subjects with dose limiting toxicities (DLTs)	During the first 3 weeks	DLTs will be assessed during the first 3 weeks of treatment. DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the DLT observation period.
Number of subjects with adverse events (AEs)	From the time of informed consent signed through 90 days after the last dose of study drug	AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment.
Objective response rate (ORR)	Up to 2 years	ORR is defined as the proportion of subjects with confirmed CR or confirmed PR.

Secondary Outcome Measures

Name	Time	Method
Time to response (TTR)	Up to 2 years	TTR is defined as the time from the start of the treatment to the first objective tumor response observed for patients who achieved CR or PR (based on RECIST Version 1.1).
Progression-free survival (PFS)	Up to 2 years	PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first (based on RECIST Version 1.1).
Overall survival (OS)	Up to 2 years	OS defined as the time from the first dose to death from any cause.
Maximum observed concentration (Cmax) of AK119 and AK112	From first dose of study drug through last dose	The PK parameters include serum concentrations of AK119 and AK112 at different timepoints after study drug administration.
Disease control rate (DCR)	Up to 2 years	DCR is defined as the proportion of subjects with CR, PR, or SD (based on RECIST Version 1.1).
Duration of response (DoR)	Up to 2 years	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.
Number of subjects who develop detectable anti-drug antibodies (ADAs)	From first dose of study drug through last dose	The immunogenicity of AK119 and AK112 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).

Trial Locations

Locations (1)

Guangdong Provincial People's Hospital; 🇨🇳 Guangzhou, China